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University of Manitoba
1.
Wang, Xiaoxia.
Molecular studies on the action of APOBEC3G against HIV-1 and development of an APOBEC-based anti-HIV approach.
Degree: Medical Microbiology, 2012, University of Manitoba
URL: http://hdl.handle.net/1993/23226
► Currently, the HIV pandemic remains a major global health challenge. In order to effectively control and cure HIV-1 infection, it is necessary to perform greater…
(more)
▼ Currently, the
HIV pandemic remains a major global health challenge. In order to effectively control and cure
HIV-
1 infection, it is necessary to perform greater research on host-
HIV interactions and develop novel preventive and therapeutic approaches. The human cytidine deaminase APOBEC3G (A3G) is the first identified host restriction factor, which can serve as an initial line of defense against
HIV-
1 by inducing lethal mutations on proviral DNA and disrupting viral reverse transcription and integration.
In order to better understand the action of A3G on
HIV-
1 replication, my study was focused on characterizing the interplay between A3G and
HIV-
1 reverse transcriptase (RT). The results indicated that A3G directly bound to RT, which contributed to A3G-mediated inhibition of viral reverse transcription. Overexpression of the RT-binding polypeptide A3G65-132 was able to disrupt wild-type A3G and RT interaction, consequently attenuating the anti-
HIV effect of A3G on
HIV replication.
While the potent antiviral activities of A3G make it an attractive candidate for gene
therapy, the actions of A3G can be counteracted by
HIV-
1 Vif during wild-type
HIV infection. In order to overcome Vif-mediated blockage and maximize the antiviral activity of A3G, this protein was fused with a virus-targeting polypeptide (R88) derived from
HIV-
1 Vpr, and various mutations were then introduced into R88-A3G fusion protein. Results showed that Vif binding mutants R88-A3GD128K and R88-A3GP129A exhibited very potent antiviral activity, and blocked
HIV-
1 replication in a CD4+ T lymphocyte cell line as well as human primary cells. In an attempt to further determine their potential against drug resistant viruses and viruses produced from latently infected cells, R88-A3GD128K was chosen and delivered by an inducible lentiviral vector system. Expression of R88-A3GD128K in actively and latently
HIV-
1 infected cells was shown to be able to inhibit the replication of both drug sensitive and resistant strains of
HIV-
1.
In conclusion, this thesis has demonstrated one of the mechanisms that how A3G can disrupt
HIV-
1 reverse transcription. Meanwhile, an A3G-based anti-
HIV-
1 strategy has been developed, which provides a proof-of-principle for a new gene
therapy approach against this deadly virus.
Advisors/Committee Members: Yao, Xiao-Jian (Medical Microbiology) (supervisor), Ball, Blake T (Medical Microbiology) Li, Yan (Medical Microbiology) Kung, Sam (Immunology) Liang, Chen (McGill University) (examiningcommittee).
Subjects/Keywords: APOBEC3G; HIV-1; gene therapy
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MLA ·
Vancouver ·
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APA (6th Edition):
Wang, X. (2012). Molecular studies on the action of APOBEC3G against HIV-1 and development of an APOBEC-based anti-HIV approach. (Thesis). University of Manitoba. Retrieved from http://hdl.handle.net/1993/23226
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Wang, Xiaoxia. “Molecular studies on the action of APOBEC3G against HIV-1 and development of an APOBEC-based anti-HIV approach.” 2012. Thesis, University of Manitoba. Accessed March 07, 2021.
http://hdl.handle.net/1993/23226.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Wang, Xiaoxia. “Molecular studies on the action of APOBEC3G against HIV-1 and development of an APOBEC-based anti-HIV approach.” 2012. Web. 07 Mar 2021.
Vancouver:
Wang X. Molecular studies on the action of APOBEC3G against HIV-1 and development of an APOBEC-based anti-HIV approach. [Internet] [Thesis]. University of Manitoba; 2012. [cited 2021 Mar 07].
Available from: http://hdl.handle.net/1993/23226.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Wang X. Molecular studies on the action of APOBEC3G against HIV-1 and development of an APOBEC-based anti-HIV approach. [Thesis]. University of Manitoba; 2012. Available from: http://hdl.handle.net/1993/23226
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of Alberta
2.
Sharma, Kumakshi.
Development of Rosette Nanotubes For HIV-1 Therapy.
Degree: MS, Department of Chemistry, 2014, University of Alberta
URL: https://era.library.ualberta.ca/files/08612q95j
► The development of therapeutics to target dendritic cells (DCs) for the treatment of diseases is of great importance, as these cells are known to play…
(more)
▼ The development of therapeutics to target dendritic
cells (DCs) for the treatment of diseases is of great importance,
as these cells are known to play an important role in antigen
processing and presentation in the immune system. Herein, we
explore the applications of biocompatible, self-assembled rosette
nanotubes (RNTs) as a therapeutic agent to deliver a HIV antigen to
the DCs. ELDKWA is linear fragment (epitope) present on the
ectodomain of HIV-1 envelope glycoprotein 41 complex, which
recognizes the galactoceramide receptors on the DC cell surface and
lysine (K) acts as a spacer between the peptide ELDKWA and the
RNTs. Our strategy is to functionalize the RNTs on the outer
surface with the bio-active peptides ELDKWAK, RGDSK and DRGSK. RGD
is a cell-adhesion peptide, which may aid in the attachment of the
HIV-1 antigen (ELDKWA) to the DC cell surface and DRG is the
scrambled version of RGD. The RNTs with the bioactive peptides were
co-mixed with fluorescently-labeled RNTs to study the cell uptake
of the RNTs.
Subjects/Keywords: HIV-1 Therapy; Peptide synthesis; Rosette Nanotubes
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APA ·
Chicago ·
MLA ·
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CSE |
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APA (6th Edition):
Sharma, K. (2014). Development of Rosette Nanotubes For HIV-1 Therapy. (Masters Thesis). University of Alberta. Retrieved from https://era.library.ualberta.ca/files/08612q95j
Chicago Manual of Style (16th Edition):
Sharma, Kumakshi. “Development of Rosette Nanotubes For HIV-1 Therapy.” 2014. Masters Thesis, University of Alberta. Accessed March 07, 2021.
https://era.library.ualberta.ca/files/08612q95j.
MLA Handbook (7th Edition):
Sharma, Kumakshi. “Development of Rosette Nanotubes For HIV-1 Therapy.” 2014. Web. 07 Mar 2021.
Vancouver:
Sharma K. Development of Rosette Nanotubes For HIV-1 Therapy. [Internet] [Masters thesis]. University of Alberta; 2014. [cited 2021 Mar 07].
Available from: https://era.library.ualberta.ca/files/08612q95j.
Council of Science Editors:
Sharma K. Development of Rosette Nanotubes For HIV-1 Therapy. [Masters Thesis]. University of Alberta; 2014. Available from: https://era.library.ualberta.ca/files/08612q95j

University of KwaZulu-Natal
3.
Sanusi, Zainab Kemi.
The mechanistic modelling of HIV-1 protease and its natural substrates: a theoretical perspective.
Degree: 2020, University of KwaZulu-Natal
URL: https://researchspace.ukzn.ac.za/handle/10413/18999
► An epidemic that has had profound impact on humanity both culturally and health-wise in recent decades is the Acquired immunodeficiency syndrome (AIDS) triggered by the…
(more)
▼ An epidemic that has had profound impact on humanity both culturally and health-wise in recent
decades is the Acquired immunodeficiency syndrome (AIDS) triggered by the Human
immunodeficiency virus (
HIV). The developments of drugs, impeding specific enzymes essential
for the replication of the
HIV-
1 virus, has been a breakthrough in the treatment of the virus. These
enzymes include the
HIV-
1 protease (PR), which is a significant degrading enzyme necessary for
the proteolytic cleavage of the Gag and Gag-Pol polyproteins, needed for the maturation of viral
protein. The catalytic mechanism of the
HIV-
1 PR of these polyproteins is a major
subject of
investigation over the past decades.
Most research on this topic explores the
HIV-
1 PR mechanism of action on its target as a stepwise
general acid-base mechanism with little or no attention to the concerted process. Among the
limitations of the stepwise reaction model is the presence of more than two transition state (TS)
steps and this led to different views on the precise rate-determining step of the reaction as well as
the protonation state of the catalytic aspartate in the active site of the
HIV-
1 PR. Likewise,
consensus on the exact recognition mechanism of the natural substrates by
HIV-
1 PR is not
forthcoming. The present study investigates the recognition approach and mechanism of reaction
of the
HIV-
1 PR with its natural substrate by a means of computational models. It is intended to
explain the cleavage mechanism of the reaction as a concerted process through the application of
in-silico techniques. This is achieved by computing the activation energies and elucidating the
quantum chemical properties of the enzyme-substrate system. An improved understanding of the
mechanism will assist in the design of new
HIV-
1 PR inhibitors.
The molecular dynamics (MD) technique with hybrid quantum mechanics and molecular
mechanics (QM/MM) method that includes the density functional theory (DFT) and Amber model
were utilized to investigate the concerted hydrolysis process. Based on previous studies in our
group involving concerted TS modeling, a six-membered ring TS pathway was first considered.
This was achieved by employing a small model system and QM methods (Hartree-Fock and DFT)
for the enzymatic mechanism of the
HIV-
1 PR. A general-acid base (GA/GB) model where both
catalytic aspartate (Asp) groups are involved in the mechanism, and the water molecule at the
active site attacks the natural substrate synchronously, was utilized. A new perspective arose from
the study where an acyclic concerted computational model offered activation energies closer to
experiment observations than the six-membered ring model. Hence, the proposed concerted
acyclic mechanism of the
HIV-
1 natural substrate within the entire protease was investigated using
both multi-layered QM/MM “Our own N-layered Integrated molecular Orbital and molecular
Mechanics” (ONIOM) theory and QM/MM MD umbrella sampling method.
A comprehensive review about experimental and theoretical…
Advisors/Committee Members: Maguire, Glenn Eamonn Mitchel. (advisor), Kruger, Hendrik Gerhardus. (advisor).
Subjects/Keywords: HIV-1 protease.; HIV/AIDs - antiretroviral therapy - drug development.; HIV-1 protease - computational models.
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❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Sanusi, Z. K. (2020). The mechanistic modelling of HIV-1 protease and its natural substrates: a theoretical perspective. (Thesis). University of KwaZulu-Natal. Retrieved from https://researchspace.ukzn.ac.za/handle/10413/18999
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Sanusi, Zainab Kemi. “The mechanistic modelling of HIV-1 protease and its natural substrates: a theoretical perspective.” 2020. Thesis, University of KwaZulu-Natal. Accessed March 07, 2021.
https://researchspace.ukzn.ac.za/handle/10413/18999.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Sanusi, Zainab Kemi. “The mechanistic modelling of HIV-1 protease and its natural substrates: a theoretical perspective.” 2020. Web. 07 Mar 2021.
Vancouver:
Sanusi ZK. The mechanistic modelling of HIV-1 protease and its natural substrates: a theoretical perspective. [Internet] [Thesis]. University of KwaZulu-Natal; 2020. [cited 2021 Mar 07].
Available from: https://researchspace.ukzn.ac.za/handle/10413/18999.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Sanusi ZK. The mechanistic modelling of HIV-1 protease and its natural substrates: a theoretical perspective. [Thesis]. University of KwaZulu-Natal; 2020. Available from: https://researchspace.ukzn.ac.za/handle/10413/18999
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of Tasmania
4.
Sullivan, AK.
Immune reconstitution in HIV-1 infection : the effects of antiretroviral and immune therapy.
Degree: 2011, University of Tasmania
URL: https://eprints.utas.edu.au/12511/3/Whole_SULLIVAN_MD_THESIS_FINAL_NOVEMBER_2011.pdf
► This thesis presents findings from two randomised, controlled pilot studies, with nested sub-studies, an observational study, a compassionate release programme and a mortality audit. It…
(more)
▼ This thesis presents findings from two randomised, controlled pilot studies, with nested sub-studies, an observational study, a compassionate release programme and a mortality audit. It aims to examine the effects, at a clinical and cellular level, of antiretroviral and immunotherapy in HIV-1 infection. Combination antiretroviral therapy (cART) enables quantitative and a degree of qualitative immune recovery; however this is neither universal nor complete. The first part of the thesis explores the effects of cART on surrogate immune markers (SIM), treatment outcomes, disease progression and death. Significant variations are observed and further re-inforced by the mortality audit. I describe for the first time patterns of SIM decline and treatment response from which a model predicting treatment outcome could be developed. This section concludes with an observational study describing a differential effect on immune restoration of different classes of cART. Together this data suggests additional therapeutic interventions will be required to address the current inadequacies of cART to fully restore HIV-1 associated immune deficiencies. Therefore, the second part of the thesis examines the effect of interleukin-2 (IL-2) therapy in different settings; with and without cART, with therapeutic immunisation and in advanced disease. In the absence of cART, IL-2 increased CD4 T-cell counts without adversely affecting viral load or immune activation, potentially delaying the need for cART initiation. The compassionate release programme also demonstrated a ‘delaying’ effect which could be exploited in patients awaiting new therapies. The main therapeutic intervention study involved IL-2 and therapeutic immunisation in the context of cART, and reports novel findings of the acute effects of IL-2, including induction of HIV-1 specific responses. Overall increases were observed in CD4+, CD4+CD28+ and CD4+CD25+ T-cells, the latter being of particular interest as the precise function of these cells in HIV-1 infection and following IL-2 therapy is still to be fully defined. As a pilot study these findings are preliminary but there is a trend for several effects to be more marked and more sustained in the arm combing all three treatments; suggesting therapeutic potential for combination immunisation and cytokine therapy which is worth pursuing. Despite the fact that the final IL-2 study in this thesis was completed in 2003, the recent publication of two large clinical outcome studies of IL-2, with somewhat unexpected results, makes these findings all the more pertinent today, and may afford some insight into the negative results observed in these large phase three trials. In summary, cART results in incomplete immune reconstitution, which can be enhanced by IL-2 and therapeutic immunisation at a cellular level. The challenge is to determine how, if at all, this can be translated into clinical benefit. Using additional SIM may help in targeting and monitoring therapy; the timing, scheduling and combination of which will be key and…
Subjects/Keywords: antiretroviral therapy; immune therapy; Immune reconstitution; HIV-1 infection
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❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Sullivan, A. (2011). Immune reconstitution in HIV-1 infection : the effects of antiretroviral and immune therapy. (Thesis). University of Tasmania. Retrieved from https://eprints.utas.edu.au/12511/3/Whole_SULLIVAN_MD_THESIS_FINAL_NOVEMBER_2011.pdf
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Sullivan, AK. “Immune reconstitution in HIV-1 infection : the effects of antiretroviral and immune therapy.” 2011. Thesis, University of Tasmania. Accessed March 07, 2021.
https://eprints.utas.edu.au/12511/3/Whole_SULLIVAN_MD_THESIS_FINAL_NOVEMBER_2011.pdf.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Sullivan, AK. “Immune reconstitution in HIV-1 infection : the effects of antiretroviral and immune therapy.” 2011. Web. 07 Mar 2021.
Vancouver:
Sullivan A. Immune reconstitution in HIV-1 infection : the effects of antiretroviral and immune therapy. [Internet] [Thesis]. University of Tasmania; 2011. [cited 2021 Mar 07].
Available from: https://eprints.utas.edu.au/12511/3/Whole_SULLIVAN_MD_THESIS_FINAL_NOVEMBER_2011.pdf.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Sullivan A. Immune reconstitution in HIV-1 infection : the effects of antiretroviral and immune therapy. [Thesis]. University of Tasmania; 2011. Available from: https://eprints.utas.edu.au/12511/3/Whole_SULLIVAN_MD_THESIS_FINAL_NOVEMBER_2011.pdf
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of Saskatchewan
5.
Mohammadzadeh, Nazanin 1990-.
ROLE OF APOBEC3 ENZYMES IN HIV-1 EVOLUTION.
Degree: 2018, University of Saskatchewan
URL: http://hdl.handle.net/10388/11676
► There are approximately 36.7 million people living with HIV while 1.8 million become newly infected every year. HIV belongs to the Retroviridae family and is…
(more)
▼ There are approximately 36.7 million people living with
HIV while
1.8 million become newly infected every year.
HIV belongs to the Retroviridae family and is an enveloped, positive sense (+) single stranded RNA virus.
HIV has two subtypes,
HIV-
1 and
HIV-2.
HIV-
1 is responsible for 95% of infections worldwide and is the focus of this thesis. There has not been any report on a conventional cure of this disease and the diagnosed
HIV+ individuals need to receive lifelong treatment with antiretroviral drugs. Besides the antiretroviral drugs, there are host restriction factors that fight the infection in addition to the conventional immune barriers and responses.
The APOBEC3 (A3) family of enzymes are part of an intrinsic immune system in humans and can act as host restriction factors to restrict the replication of
HIV in CD4+ T cells by deaminating cytosine to uracil on the (-) DNA of
HIV during reverse transcription. This promutagenic activity, if it occurs frequently enough, can cause viral hypermutation and inactivation. The A3 family contains seven members (A3A to A3H, excluding A3E) some of which developed gene variations that result in protein polymorphisms due to selective pressure over evolutionary time. These polymorphisms acquired enhanced antiretroviral activity to fight off
HIV. To combat this,
HIV has an accessory protein termed virion infectivity factor (Vif) that interacts with A3 enzymes and components of a Cullin5 E3 ligase complex. This complex causes ubiquitination and degradation of A3 enzymes in
HIV infected host cells.
HIV also has a high level of genetic variation that allows the virus to escape immunological and pharmacological barriers. Besides the lack of proofreading activity of reverse transcriptase, viral recombination and high rate of replication, the A3 enzymes have a potential role in increasing the genetic diversity of the
HIV replicating pool if Vif mediated degradation is not complete. As a result, human A3 enzymes can contribute to this diversity directly by causing sublethal mutations and indirectly when the lethally mutated RNA genomes are “rescued” after virus recombination. While A3 enzymes may have this potential, and some research has found that A3 enzymes cause drug resistance mutations, other research groups have reported that in the presence of Vif the mutation rate of A3s is lower than the mutation rate of reverse transcriptase and their contribution to
HIV evolution is not significant.
To identify all the contributors to genetic variation of
HIV and have a reliable answer for the current controversy in the field we aimed to determine the mutation rate of A3s in wild-type
HIV-
1 infection and investigate if A3-induced mutations can yield drug resistant
HIV-
1 variants. Moreover, we aimed to study the restriction abilities of A3F allele variants carrying a single nucleotide polymorphism (SNP). We chose the SNP that causes the A3F 231I/V polymorphism because most people carry the heterozygous alleles.
To test if A3 enzymes could contribute to
HIV-
1 evolution, we established a…
Advisors/Committee Members: Chelico, Linda, Bull, Harold, Xiao, Wei, Misra, Vikram.
Subjects/Keywords: APOBEC3F; APOBEC3G; drug resistance; HIV-1; mutagenesis; restriction factors; antiretroviral therapy
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❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Mohammadzadeh, N. 1. (2018). ROLE OF APOBEC3 ENZYMES IN HIV-1 EVOLUTION. (Thesis). University of Saskatchewan. Retrieved from http://hdl.handle.net/10388/11676
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Mohammadzadeh, Nazanin 1990-. “ROLE OF APOBEC3 ENZYMES IN HIV-1 EVOLUTION.” 2018. Thesis, University of Saskatchewan. Accessed March 07, 2021.
http://hdl.handle.net/10388/11676.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Mohammadzadeh, Nazanin 1990-. “ROLE OF APOBEC3 ENZYMES IN HIV-1 EVOLUTION.” 2018. Web. 07 Mar 2021.
Vancouver:
Mohammadzadeh N1. ROLE OF APOBEC3 ENZYMES IN HIV-1 EVOLUTION. [Internet] [Thesis]. University of Saskatchewan; 2018. [cited 2021 Mar 07].
Available from: http://hdl.handle.net/10388/11676.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Mohammadzadeh N1. ROLE OF APOBEC3 ENZYMES IN HIV-1 EVOLUTION. [Thesis]. University of Saskatchewan; 2018. Available from: http://hdl.handle.net/10388/11676
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of Nairobi
6.
Ngare, Stanley M.
Prevalence of hypertension and cardiovascular risk factors in HIV-1 infected patients on anti-retroviral therapy
.
Degree: 2009, University of Nairobi
URL: http://erepository.uonbi.ac.ke:8080/xmlui/handle/123456789/30801
► Background: With increased use of HAART in HIV-infected individuals there is concern that anti-retrovirals may be associated with hypertension, a known cardiovascular risk factor. This…
(more)
▼ Background: With increased use of HAART in HIV-infected individuals there is concern that
anti-retrovirals may be associated with hypertension, a known cardiovascular risk factor. This
association could be related to duration of therapy, or the metabolic complications associated
with HAART or finally to certain specific anti-retrovirals.
Objective: To determine the period prevalence of hypertension in HAART experienced
patients and compare this to the period prevalence of HAART naive patients and to determine
the cardiovascular risk factors of these patients attending the Kenyatta National Hospital.
Design: A cross-sectional comparison study.
Setting: Kenyatta National Hospital, a tertiary health care facility.
Subjects: Consenting HIV- infected adults who where anti-retroviral naive or had been on
anti-retrovirals for two years or more.
Outcome measures: Prevalence of hypertension; associated cardiovascular risk factors-age,
gender, body mass index, dyslipidemia defined as presence of any of the following lipid
abnormalities: raised total or LDL- cholesterol, low HDL cholesterol, or raised triglycerides;
and dysglycemia defined as presence of any of the following: impaired fasting glucose or diabetes mellitus.
Results: Between July and November 2008, 3528 patients were screened, 1305 met the case
definitions, 63% of whom were females .Of these 620 patients were recruited into
anti-retroviral experienced group and 615 patients were recruited into the anti-retroviral naive
group. Majority of the patients (95.6%) were on a non-nucleoside reverse transcriptase. At a
median of 2.4 years the prevalence of hypertension was 12.9% ( 95% CI 5.1-20.9) in the
HAART experienced patients and 14.3 %( 95%CI 5.9-22.1) in the HAART naive group
(p=0.507). Dyslipidemia was the most common cardiovascular risk factor in 71.3% of the
hypertensive patient on HAART. There was no statistical difference in the prevalence of
dyslipidemia in HAART naive patients (p~0.299). Among the HAART experienced patients
dysglycemia was noted in 35% of patients and 27.3% of HAART naive patients (p=0.23).
Conclusion: At a median of 2.4 years on HAART there was no increased prevalence of
hypertension compared to HAART naive patients. Dyslipidemia and dysglycemia are
important cardiovascular risk factors in hypertensive HIV populations, especially in patients
on HAART. Therefore there is need to actively screen this hypertensive population for both of these risk factors.
Subjects/Keywords: Antiretroviral therapy;
Cardiovascular risk factors;
Hypertension;
HIV-1
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❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Ngare, S. M. (2009). Prevalence of hypertension and cardiovascular risk factors in HIV-1 infected patients on anti-retroviral therapy
. (Thesis). University of Nairobi. Retrieved from http://erepository.uonbi.ac.ke:8080/xmlui/handle/123456789/30801
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Ngare, Stanley M. “Prevalence of hypertension and cardiovascular risk factors in HIV-1 infected patients on anti-retroviral therapy
.” 2009. Thesis, University of Nairobi. Accessed March 07, 2021.
http://erepository.uonbi.ac.ke:8080/xmlui/handle/123456789/30801.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Ngare, Stanley M. “Prevalence of hypertension and cardiovascular risk factors in HIV-1 infected patients on anti-retroviral therapy
.” 2009. Web. 07 Mar 2021.
Vancouver:
Ngare SM. Prevalence of hypertension and cardiovascular risk factors in HIV-1 infected patients on anti-retroviral therapy
. [Internet] [Thesis]. University of Nairobi; 2009. [cited 2021 Mar 07].
Available from: http://erepository.uonbi.ac.ke:8080/xmlui/handle/123456789/30801.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Ngare SM. Prevalence of hypertension and cardiovascular risk factors in HIV-1 infected patients on anti-retroviral therapy
. [Thesis]. University of Nairobi; 2009. Available from: http://erepository.uonbi.ac.ke:8080/xmlui/handle/123456789/30801
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
7.
Perrin, Sophie.
Vieillissement, infection par le VIH-1 & traitements antirétroviraux : Postprandial lipemia and lactoferrin : the Lipolysis Stimulated Receptor as a potential target.
Degree: Docteur es, Pathologie humaine, 2012, Aix Marseille Université
URL: http://www.theses.fr/2012AIXM5058
► L'utilisation des antirétroviraux (ART) a permis une augmentation de la durée des patients infectés par le VIH. Par ailleurs, les comorbidités, retrouvées au cours du…
(more)
▼ L'utilisation des antirétroviraux (ART) a permis une augmentation de la durée des patients infectés par le VIH. Par ailleurs, les comorbidités, retrouvées au cours du vieillissement physiologique, semblent être plus fréquentes et d'apparition plus précoce ce qui pourrait suggérer une modification du programme de vieillissement chez ces patients. L'étude ANRS EP45 « Aging » (clinicalTrials.gov, NCT01038999) a pour objectif d'analyser chez des patients infectés par le VIH traités ou non les mécanismes cellulaires connus pour être impliqués dans le vieillissement. Les PBMC d'une cohorte de 130 patients infectés par le VIH 1 appariés en âge et en sexe avec 49 sujets séronégatifs ont été analysés. Trois centres spécialisés (Marseille, Montpellier, Nice) ont recruté des patients infectés naïfs ou sous première ligne de traitement. Les résultats présentés dans ce manuscrit rapportent l'analyse des mitochondries et des lamines nucléaires. La maturation de la lamine A ne semble pas modifiée dans les PBMC de patients sous traitement contenant un inhibiteur de protéase. Cependant, ces cellules pourraient ne pas être le modèle le plus adapté pour explorer ce volet. D'autre part, l'infection est responsable d'anomalies mitochondriales dans les lymphocytes, partiellement corrigées par les traitements antirétroviraux qui modifient les mitochondries des monocytes moins sensibles à l'infection. Bien que les secondes générations de ART soient moins toxiques que les premières, leurs effets secondaires pourraient néanmoins, sur « le long terme » et/ou généralisés à l'ensemble de l'organisme, être l'un des facteurs modifiant le programme de vieillissement de ces patients.
Antiretroviral therapy (ART) has increased life expectancy in HIV-infected patients. Moreover, some age-related disorders were found to be more frequent in HIV infected and treated patients than in an age-matched general population, suggesting a modified time course of aging in HIV infected patients. The ANRS EP45 « Aging » study (clinicalTrials.gov, NCT01038999) investigated in PBMC from HIV-1 infected patients under treatment or not the cellular mechanisms known to be involved in aging. The study was performed on a cohort of 130 patients HIV-1 infected age- and sex-matched with 49 seronegative control subjects. Patients never treated with ART (naïve) or under first line were recruited by 3 AIDS centres (Marseille, Montpellier, Nice). Results presented here describe explorations of mitochondria and nuclear lamin. No alteration of lamin A maturation was detected in PBMC from HIV-1 infected patients under treatment with protease inhibitor. However, these cells could not be the most appropriate models to investigate lamin A-related aging pathway. On another hand, mitochondrial modifications were observed in lymphocytes from HIV infected naive patients. These alterations were only partly rescued by ART whereas its induced slight changes in monocytes that appeared to be less sensitive to infection. While second generation of ART are less toxic than the first one, their…
Advisors/Committee Members: Cau, Pierre (thesis director).
Subjects/Keywords: Vih-1; Antirétroviraux; Vieillissement; Mitochondrie; Lamines; Hiv-1; Antiretroviral therapy; Aging; Mitochondria; Lamin
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❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Perrin, S. (2012). Vieillissement, infection par le VIH-1 & traitements antirétroviraux : Postprandial lipemia and lactoferrin : the Lipolysis Stimulated Receptor as a potential target. (Doctoral Dissertation). Aix Marseille Université. Retrieved from http://www.theses.fr/2012AIXM5058
Chicago Manual of Style (16th Edition):
Perrin, Sophie. “Vieillissement, infection par le VIH-1 & traitements antirétroviraux : Postprandial lipemia and lactoferrin : the Lipolysis Stimulated Receptor as a potential target.” 2012. Doctoral Dissertation, Aix Marseille Université. Accessed March 07, 2021.
http://www.theses.fr/2012AIXM5058.
MLA Handbook (7th Edition):
Perrin, Sophie. “Vieillissement, infection par le VIH-1 & traitements antirétroviraux : Postprandial lipemia and lactoferrin : the Lipolysis Stimulated Receptor as a potential target.” 2012. Web. 07 Mar 2021.
Vancouver:
Perrin S. Vieillissement, infection par le VIH-1 & traitements antirétroviraux : Postprandial lipemia and lactoferrin : the Lipolysis Stimulated Receptor as a potential target. [Internet] [Doctoral dissertation]. Aix Marseille Université 2012. [cited 2021 Mar 07].
Available from: http://www.theses.fr/2012AIXM5058.
Council of Science Editors:
Perrin S. Vieillissement, infection par le VIH-1 & traitements antirétroviraux : Postprandial lipemia and lactoferrin : the Lipolysis Stimulated Receptor as a potential target. [Doctoral Dissertation]. Aix Marseille Université 2012. Available from: http://www.theses.fr/2012AIXM5058

University of Florida
8.
Roff, Shannon R.
T-Cell Based HIV Vaccines.
Degree: PhD, Veterinary Medical Sciences - Veterinary Medicine, 2015, University of Florida
URL: https://ufdc.ufl.edu/UFE0049592
► One of the most important research missions since the discovery of antiretroviral therapy (ART) is the development of a safe and effective HIV-1 vaccine. After…
(more)
▼ One of the most important research missions since the discovery of antiretroviral
therapy (ART) is the development of a safe and effective
HIV-
1 vaccine. After 30 years of research, and effective conventional vaccine targeting the antibody response has been unsuccessful. Through careful evaluation of data from these clinical trials, most scientists agree that an effective
HIV vaccine should include both humoral (antibody) and cell-mediated responses, with cytotoxic T lymphocytes (CTL) playing critical roles in control of the virus. The central hypothesis of this project is that the multi-antigenic T-cell immunity to lentiviral epitopes, consisting of both CD4+ and CD8+ T cells and polyfunctional T cells will generate the most potent and persistent vaccine immunity against all tiers of
HIV-
1 isolates. To target CTL epitopes that are reactive against global
HIV-
1 isolates, we evaluated not only
HIV epitopes that are highly conserved within viral clades, but also epitopes that have a high degree of homology, or are conserved between lentiviruses of different species (FIV, SIV and
HIV-
1). Using these lentivirally conserved epitopes, we have developed and are testing a novel vaccine strategy using multi-antigenic peptide vaccines (MAP) stimulating anti-lentiviral T-cell immunity. Utilizing T-cell targeting to augment conventional vaccination strategies will result in the development of a novel and effective vaccine against global isolates of
HIV-
1. ( en )
Advisors/Committee Members: YAMAMOTO,JANET K (committee chair), ABBOTT,JEFFREY R (committee member), PECK,AMMON B (committee member), WALLET,MARK ANDREW (committee member).
Subjects/Keywords: AIDS; Antigens; Epitopes; Feline immunodeficiency virus; HIV; HIV 1; HLA antigens; Infections; Interferons; Vaccinations; antiretrovial – hiv-1 – t-cell – therapy – vaccine; City of Coleman ( local )
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❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Roff, S. R. (2015). T-Cell Based HIV Vaccines. (Doctoral Dissertation). University of Florida. Retrieved from https://ufdc.ufl.edu/UFE0049592
Chicago Manual of Style (16th Edition):
Roff, Shannon R. “T-Cell Based HIV Vaccines.” 2015. Doctoral Dissertation, University of Florida. Accessed March 07, 2021.
https://ufdc.ufl.edu/UFE0049592.
MLA Handbook (7th Edition):
Roff, Shannon R. “T-Cell Based HIV Vaccines.” 2015. Web. 07 Mar 2021.
Vancouver:
Roff SR. T-Cell Based HIV Vaccines. [Internet] [Doctoral dissertation]. University of Florida; 2015. [cited 2021 Mar 07].
Available from: https://ufdc.ufl.edu/UFE0049592.
Council of Science Editors:
Roff SR. T-Cell Based HIV Vaccines. [Doctoral Dissertation]. University of Florida; 2015. Available from: https://ufdc.ufl.edu/UFE0049592

University of South Carolina
9.
McLaurin, Kristen Addie.
Theraputic Strategies for Altering the Trajectory of Neurocognitive Impairments in HIV-1 Associated Neurocognitive Disorders in the Post-Cart Era.
Degree: PhD, Psychology, 2020, University of South Carolina
URL: https://scholarcommons.sc.edu/etd/5808
► The marked increase in life expectancy for individuals with human immunodeficiency virus type 1 (HIV-1), following the great success of combination antiretroviral therapy (cART),…
(more)
▼ The marked increase in life expectancy for individuals with human immunodeficiency virus type
1 (
HIV-
1), following the great success of combination antiretroviral
therapy (cART), necessitates an investigation of the progression of
HIV-
1 associated neurocognitive disorders (HAND), and associated neural mechanisms, across the functional lifespan. Furthermore, given the persistence of HAND in the post-cART era, there remains a critical need to develop adjunctive therapeutics targeting the neural mechanisms underlying HAND. Thus, the guiding hypothesis for the present study was threefold. First, that there will be a differential progression of NCI in
HIV-
1 Tg and control animals. Second, that synaptodendritic dysfunction will mechanistically underlie NCI and progress throughout the early lifespan. Third, that the altered developmental trajectory of NCI, as a function of the
HIV-
1 transgene, will be restored with SE, targeting synaptodendritic dysfunction. Neurocognitive and neuroanatomical assessments were utilized to critically test these hypotheses.
The
HIV-
1 transgenic (Tg) rat, resembling
HIV-
1 seropositive individuals on lifelong cART, exhibits age-related progressive neurocognitive impairments in the absence of sensory or motor system deficits and comorbidities. Independent of biological sex, the
HIV-
1 Tg rat exhibits a differential progression of long-term episodic memory, temporal processing, stimulus-reinforcement learning, sustained attention, and flexibility and inhibition. Synaptic dysfunction in pyramidal neurons from layers II-III of the medial prefrontal cortex (mPFC) were characterized by alterations in dendritic branching complexity, synaptic connectivity and dendritic spine morphology.
Critically testing the therapeutic efficacy of SE in the
HIV-
1 Tg rat revealed an innovative therapeutic approach for the prevention of NCI in HAND; a therapeutic that, at least partially, restores the developmental trajectory of neurocognitive function. Mechanistically, SE remodels neuronal circuitry at the synaptic level, evidenced by profound long-term modifications in neuronal morphology and dendritic spines in pyramidal neurons from layers II-III of the mPFC.
A longitudinal experimental design was subsequently utilized to assess the progression of synaptic function from postnatal day (PD) 30 to PD 180. Prominent developmental alterations in regressive (i.e., pruning) processes, as well as synaptic function, were observed, independent of biological sex, in pyramidal neurons from layers II-III of the mPFC in the
HIV-
1 Tg rat, supporting a key neural mechanism underlying HAND. Taken together, the present studies have defined HAND as a neurodegenerative disease characterized by age-related, progressive neurocognitive impairments and synaptic dysfunction; a disease which can be modified by therapeutics (i.e., SE) that mechanistically target synaptic dysfunction.
Advisors/Committee Members: Charles F. Mactutus.
Subjects/Keywords: Psychology; combination antiretroviral therapy; cART; HIV-1 associated neurocognitive disorders; HAND; post-cART
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❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
McLaurin, K. A. (2020). Theraputic Strategies for Altering the Trajectory of Neurocognitive Impairments in HIV-1 Associated Neurocognitive Disorders in the Post-Cart Era. (Doctoral Dissertation). University of South Carolina. Retrieved from https://scholarcommons.sc.edu/etd/5808
Chicago Manual of Style (16th Edition):
McLaurin, Kristen Addie. “Theraputic Strategies for Altering the Trajectory of Neurocognitive Impairments in HIV-1 Associated Neurocognitive Disorders in the Post-Cart Era.” 2020. Doctoral Dissertation, University of South Carolina. Accessed March 07, 2021.
https://scholarcommons.sc.edu/etd/5808.
MLA Handbook (7th Edition):
McLaurin, Kristen Addie. “Theraputic Strategies for Altering the Trajectory of Neurocognitive Impairments in HIV-1 Associated Neurocognitive Disorders in the Post-Cart Era.” 2020. Web. 07 Mar 2021.
Vancouver:
McLaurin KA. Theraputic Strategies for Altering the Trajectory of Neurocognitive Impairments in HIV-1 Associated Neurocognitive Disorders in the Post-Cart Era. [Internet] [Doctoral dissertation]. University of South Carolina; 2020. [cited 2021 Mar 07].
Available from: https://scholarcommons.sc.edu/etd/5808.
Council of Science Editors:
McLaurin KA. Theraputic Strategies for Altering the Trajectory of Neurocognitive Impairments in HIV-1 Associated Neurocognitive Disorders in the Post-Cart Era. [Doctoral Dissertation]. University of South Carolina; 2020. Available from: https://scholarcommons.sc.edu/etd/5808

IUPUI
10.
Shaw, Aaron Marcus.
Advancing the Safety of Lentiviral Vector Mediated Gene Therapy.
Degree: 2015, IUPUI
URL: http://hdl.handle.net/1805/7925
► Indiana University-Purdue University Indianapolis (IUPUI)
Lentiviral vector mediated gene therapy has made great strides in recent years with several successful clinical trials. However, adverse events…
(more)
▼ Indiana University-Purdue University Indianapolis (IUPUI)
Lentiviral vector mediated gene therapy has made great strides in recent years with several successful clinical trials. However, adverse events encountered with some early trials have highlighted the necessity to improve upon its safety. Improvements can range from early steps in vector production to evaluation of insertion sites post-transduction. We have evaluated an FDA approved DNase for removal of residual plasmid DNA during vector production, developed novel non-integrating lentiviral vectors and employed modified insertion site analysis post-transduction to improve the safety of lentiviral vector mediated gene therapy.
To prevent the exposure of gene therapy patients to HIV-1 DNA it is essential to remove residual plasmid DNA during vector production. We evaluated a recombinant human DNase which has been FDA approved for use in patients as an alternative to a bacterially derived DNase. Our results indicate this DNase is an effective alternative with a potentially safer profile for use in patients.
The ability of lentiviral vectors to stably integrate their genome into a host cell’s DNA can have negative side-effects due to the risk of insertional mutagenesis. Non-integrating lentiviral vectors have been developed to alleviate this risk in applications where integration is not necessary. However, a low frequency of illegitimate integration persists when using these vectors. We have developed a novel non-integrating vector mutation and evaluated the efficacy of combining it with other mutations for reducing the frequency of illegitimate integration. We demonstrate that combining mutations that inhibit integration can further reduce the frequency of illegitimate integration.
Several methodologies have been developed for evaluating the insertion sites of normal integrating lentiviral vectors. Illegitimate integration by non-integrating vectors demonstrates mechanisms which result in insertions and/or deletions at the vector-genome junction. Current methods lack the sensitivity to account for these variables in a high-throughput manner. We have adapted modifications to current methods to improve the capture of these variable insertion sites for analysis.
The results of these studies improve the safety of lentiviral vector mediated gene therapy by improving the purity of the vector product, providing a safer vector for non-integrase mediated applications, and allowing more sensitive analysis of insertion sites post-transduction.
Advisors/Committee Members: Cornetta, Kenneth.
Subjects/Keywords: Gene Therapy; lentiviral; HIV-1; non-integrating; episome; vector production; insertion site analysis
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❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Shaw, A. M. (2015). Advancing the Safety of Lentiviral Vector Mediated Gene Therapy. (Thesis). IUPUI. Retrieved from http://hdl.handle.net/1805/7925
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Shaw, Aaron Marcus. “Advancing the Safety of Lentiviral Vector Mediated Gene Therapy.” 2015. Thesis, IUPUI. Accessed March 07, 2021.
http://hdl.handle.net/1805/7925.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Shaw, Aaron Marcus. “Advancing the Safety of Lentiviral Vector Mediated Gene Therapy.” 2015. Web. 07 Mar 2021.
Vancouver:
Shaw AM. Advancing the Safety of Lentiviral Vector Mediated Gene Therapy. [Internet] [Thesis]. IUPUI; 2015. [cited 2021 Mar 07].
Available from: http://hdl.handle.net/1805/7925.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Shaw AM. Advancing the Safety of Lentiviral Vector Mediated Gene Therapy. [Thesis]. IUPUI; 2015. Available from: http://hdl.handle.net/1805/7925
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of KwaZulu-Natal
11.
Ferreira, Isabella Anna Theresa Markham.
Identifying the cellular HIV-1 reservoir in lymph nodes of antiretroviral therapy suppressed individuals.
Degree: 2019, University of KwaZulu-Natal
URL: https://researchspace.ukzn.ac.za/handle/10413/18684
► HIV-1 infection is suppressed but not cured in the face of antiretroviral therapy (ART). Pinpointing the cellular HIV-1 reservoir, which allows HIV-1 to persist, is…
(more)
▼ HIV-
1 infection is suppressed but not cured in the face of antiretroviral
therapy (ART). Pinpointing the cellular
HIV-
1 reservoir, which allows
HIV-
1 to persist, is key to the eradication of the virus. Lymph nodes are known to be a reservoir site for
HIV-
1 persistence, and we have assembled lymph nodes from a cross-sectional cohort of participants on suppressive ART to better understand the cellular
HIV-
1 reservoir. We developed a novel single-cell RNA-Seq methodology to identify the cellular
HIV-
1 reservoir in the lymph node compartment in ART suppressed individuals.
HIV-
1 positive cells from these lymph nodes were stained with anti-
HIV-
1 antibodies and selected using flow cytometric sorting. Seq-Well, a high throughput single-cell
RNA-Seq approach, was then performed to detect gag and env
HIV-
1 transcripts in individual cells, as well as the infected subtype using the cellular transcriptome. In parallel, the consensus near full length viral clone from the lymph node was sequenced and used for alignment. Using our methods for identifying
HIV-
1 infected cells from lymph nodes from chronically infected individuals, we have identified both known and novel putative host markers that are associated with persistent infection. These included co-expression of APOBEC3G, NFAT5, and NFKB2 in cells that contained
HIV-
1 mRNA. Our results show that cells with transcriptomes consistent with a T cell origin are the main infected population, and we are in the process of deeply characterizing the cell subtypes involved that also express markers of
HIV-
1 infection.
Advisors/Committee Members: Sigal, Alexander. (advisor).
Subjects/Keywords: Lymph nodes.; HIV-1.; Antiretroviral Therapy.; Cell subtypes.; Viruses.; Public health.; Transcriptome.
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❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Ferreira, I. A. T. M. (2019). Identifying the cellular HIV-1 reservoir in lymph nodes of antiretroviral therapy suppressed individuals. (Thesis). University of KwaZulu-Natal. Retrieved from https://researchspace.ukzn.ac.za/handle/10413/18684
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Ferreira, Isabella Anna Theresa Markham. “Identifying the cellular HIV-1 reservoir in lymph nodes of antiretroviral therapy suppressed individuals.” 2019. Thesis, University of KwaZulu-Natal. Accessed March 07, 2021.
https://researchspace.ukzn.ac.za/handle/10413/18684.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Ferreira, Isabella Anna Theresa Markham. “Identifying the cellular HIV-1 reservoir in lymph nodes of antiretroviral therapy suppressed individuals.” 2019. Web. 07 Mar 2021.
Vancouver:
Ferreira IATM. Identifying the cellular HIV-1 reservoir in lymph nodes of antiretroviral therapy suppressed individuals. [Internet] [Thesis]. University of KwaZulu-Natal; 2019. [cited 2021 Mar 07].
Available from: https://researchspace.ukzn.ac.za/handle/10413/18684.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Ferreira IATM. Identifying the cellular HIV-1 reservoir in lymph nodes of antiretroviral therapy suppressed individuals. [Thesis]. University of KwaZulu-Natal; 2019. Available from: https://researchspace.ukzn.ac.za/handle/10413/18684
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of Pennsylvania
12.
Sosale, Nisha Gowri.
Inhibiting Phagocytosis With Cd47: From the Effects of Red Cell Rigidity and Shape to Display on Lentivirus - Implications for Aging and Gene Therapy.
Degree: 2014, University of Pennsylvania
URL: https://repository.upenn.edu/edissertations/1451
► A macrophage engulfs another cell, or foreign particle, via phagocytosis, an engulfment process crucial not only to innate and adaptive immunity, but also to the…
(more)
▼ A macrophage engulfs another cell, or foreign particle, via phagocytosis, an engulfment process crucial not only to innate and adaptive immunity, but also to the maintenance of homeostasis. Phagocytosis is a receptor-mediated process that is dependent on Myosin-IIA motors, among other cytoskeletal proteins. Adhesion processes of both hematopoietic and mesenchymal derived cells can activate Myosin, and increasingly so on rigid substrates. Macrophage engulfment becomes inefficient if the macrophage also engages `Marker of Self' CD47 that inhibits Myosin accumulation to the phagocytic synapse. CD47 is a ubiquitously expressed transmembrane cell surface protein that binds to signal regulatory protein alpha (SIRPA) that is highly expressed by macrophages. CD47's role in downregulating macrophage phagocytosis was first discovered in murine erythrocytes (RBCs), where wild-type RBCs are long-lived in circulation, while RBCs derived from a CD47 knockout mouse are rapidly cleared. More recently CD47 has been found to inhibit clearance of a variety of viable cell types including stem cells, leukocytes, platelets, and cancers. However, the limitations of CD47 as a `marker of self' on apoptotic and experimentally oxidized cells are beginning to be realized, as CD47 surface expression does not effectively inhibit the phagocytosis of these aged cells.
Furthermore, while it is well known that macrophage-mediated clearance controls the removal of aged RBCs, that are reported to become rigid, from the bloodstream, the role that rigidification plays in countering CD47 inhibitory signals remains to be clarified. To study the effects of RBC rigidity on the regulation of phagocytosis by CD47 expression, RBCs were controllably stiffened in different shapes without compromising CD47-SIRPA interactions. Uptake of antibody-opsonized human-RBC was accelerated, as expected, by blocking CD47, but was fastest with rigid RBC-Discocytes that mediated maximum levels of Myosin-IIA accumulation at the phagocytic synapse. Attenuation of the antibody-driven `eat me' signal partially recovered `Self' signaling by rigid RBC-Discocytes, and more rounded but rigid RBC-Stomatocytes also signaled `Self' more efficiently. These results highlight the biophysical nature of the CD47-SIRPA inhibitory mechanism that can be overpowered by rigidity and can be rescued by target shape.
Resident tissue macrophages are adept in capturing non-self particles from the extracellular environment, including HIV-derived lentiviral gene therapy vectors, thus limiting efforts at therapeutic vector delivery. CD47-SIRPA inhibition has just recently been shown to inhibit in vivo macrophage clearance of nano-sized synthetic particles that are significantly smaller than previously studied mammalian cells. A novel lentiviral vector was engineered here to present an oriented human CD47-GFP fusion protein on the vector envelope. Using Total internal reflection microscopy (TIRFM), atomic force microscopy (AFM), and immunoblotting, we have demonstrated that engineered lentivectors display…
Subjects/Keywords: CD47; HIV-1; lentiviral gene therapy; mechanosensitive; phagocytosis; red blood cell; Biophysics; Chemical Engineering; Virology
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❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Sosale, N. G. (2014). Inhibiting Phagocytosis With Cd47: From the Effects of Red Cell Rigidity and Shape to Display on Lentivirus - Implications for Aging and Gene Therapy. (Thesis). University of Pennsylvania. Retrieved from https://repository.upenn.edu/edissertations/1451
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Sosale, Nisha Gowri. “Inhibiting Phagocytosis With Cd47: From the Effects of Red Cell Rigidity and Shape to Display on Lentivirus - Implications for Aging and Gene Therapy.” 2014. Thesis, University of Pennsylvania. Accessed March 07, 2021.
https://repository.upenn.edu/edissertations/1451.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Sosale, Nisha Gowri. “Inhibiting Phagocytosis With Cd47: From the Effects of Red Cell Rigidity and Shape to Display on Lentivirus - Implications for Aging and Gene Therapy.” 2014. Web. 07 Mar 2021.
Vancouver:
Sosale NG. Inhibiting Phagocytosis With Cd47: From the Effects of Red Cell Rigidity and Shape to Display on Lentivirus - Implications for Aging and Gene Therapy. [Internet] [Thesis]. University of Pennsylvania; 2014. [cited 2021 Mar 07].
Available from: https://repository.upenn.edu/edissertations/1451.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Sosale NG. Inhibiting Phagocytosis With Cd47: From the Effects of Red Cell Rigidity and Shape to Display on Lentivirus - Implications for Aging and Gene Therapy. [Thesis]. University of Pennsylvania; 2014. Available from: https://repository.upenn.edu/edissertations/1451
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of KwaZulu-Natal
13.
Folarin, Eniola Lilian.
Molecular analysis of human immuno-deficiency virus-1 (South African subtype C) protease drug resistance mutations emerging on Darunavir therapy.
Degree: 2020, University of KwaZulu-Natal
URL: https://researchspace.ukzn.ac.za/handle/10413/19008
► Human immunodeficiency virus as the causative agent of acquired immune deficiency syndrome remains a serious infectious disease and the leading cause of deaths worldwide. According…
(more)
▼ Human immunodeficiency virus as the causative agent of acquired immune deficiency
syndrome remains a serious infectious disease and the leading cause of deaths worldwide.
According to UNAIDS, approximately 37 million individuals are living with
HIV/AIDS and
770,000 AIDS related deaths.
HIV-
1 subtype C strain is responsible for approximately 70 %
of individuals living with
HIV. Even with this staggering statistic, not many studies have been
conducted on this subtype.
Currently, there exist no treatment that completely eradicates the virus from an infected
individual. Although, three enzymes required by the virus to undergo intracellular replication
have been targeted to delay the progression of the disease, these enzymes include; reverse
transcriptase crucial for completion of the initial stages of
HIV replication, integrase essential
for the integration of pro-viral DNA into the host chromosomal DNA and finally the enzyme
for which this study will focus only is protease which is vital for the development and assembly
of infectious viral progeny. The
HIV aspartyl protease plays a major role in the life cycle of
the virus and has long been a target in antiviral
therapy. This advancements in the knowledge
of
HIV biology, pathogenesis and pharmacology has led to unprecedented efforts to interpret
basic findings in the development of novel antiviral drug therapies.
Nonetheless, the emergence of drug resistant mutations has hampered the efficacy of
HIV-
1
protease inhibition
therapy. These mutations reduce the binding affinity of inhibitors while
maintaining viable catalytic activity and affinity for the natural substrate. In
HIV-
1 protease,
mutations at the following positions V32I, I50V,154M, and I84V are associated with subtle
structural changes that confer resistance to protease inhibitors especially darunavir. These
mutations located at or adjacent to the active site cavity, compromise drug susceptibility due
to weak Van der Waals interaction and binding site distortion resulting in treatment failure. In
this study we analysed the functional effects of these mutations on the
HIV-
1 South African
subtype C protease. To understand how these mutations influence drug susceptibility in HIV1 CSA protease, the mutations were introduced by site directed mutagenesis and confirmed by
DNA sequencing. Over-expression and purification of wild-type and mutant protease.
Followed by enzyme kinetics, inhibition (Ki) and thermodynamics studies carried out against
six clinically approved drugs. Significant difference was not observed in the substrate affinity
of the variant protease compared to the wildtype C-SA protease with a Michaelis constant (Km)
values of 104 and 124 µM and turnover number (Kcat) of approximately 2.2 and 0.2 s-
1 for
variant and wildtype protease respectively. The six clinically approved drugs used in this study
demonstrated reduced binding affinities and weaker inhibition towards the variant protease in
comparison to the wild-type
HIV-
1 protease. Atazanavir, amprenavir, darunavir and…
Advisors/Committee Members: Kruger, Hendrik Gerhardus. (advisor), Lin, Johnson. (advisor).
Subjects/Keywords: Novel antiviral drug therapies.; HIV and AIDS.; HIV-1 protease inhibition therapy.; Highly active anti-retroviral therapy (HAART).; HIV - protease drug resistance.; Darunavir.
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APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
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to Zotero / EndNote / Reference
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APA (6th Edition):
Folarin, E. L. (2020). Molecular analysis of human immuno-deficiency virus-1 (South African subtype C) protease drug resistance mutations emerging on Darunavir therapy. (Thesis). University of KwaZulu-Natal. Retrieved from https://researchspace.ukzn.ac.za/handle/10413/19008
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Folarin, Eniola Lilian. “Molecular analysis of human immuno-deficiency virus-1 (South African subtype C) protease drug resistance mutations emerging on Darunavir therapy.” 2020. Thesis, University of KwaZulu-Natal. Accessed March 07, 2021.
https://researchspace.ukzn.ac.za/handle/10413/19008.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Folarin, Eniola Lilian. “Molecular analysis of human immuno-deficiency virus-1 (South African subtype C) protease drug resistance mutations emerging on Darunavir therapy.” 2020. Web. 07 Mar 2021.
Vancouver:
Folarin EL. Molecular analysis of human immuno-deficiency virus-1 (South African subtype C) protease drug resistance mutations emerging on Darunavir therapy. [Internet] [Thesis]. University of KwaZulu-Natal; 2020. [cited 2021 Mar 07].
Available from: https://researchspace.ukzn.ac.za/handle/10413/19008.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Folarin EL. Molecular analysis of human immuno-deficiency virus-1 (South African subtype C) protease drug resistance mutations emerging on Darunavir therapy. [Thesis]. University of KwaZulu-Natal; 2020. Available from: https://researchspace.ukzn.ac.za/handle/10413/19008
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of Gothenburg / Göteborgs Universitet
14.
Sörstedt, Erik.
Antiretroviral treatment of HIV-1 in Sweden with focus on virological aspects.
Degree: 2021, University of Gothenburg / Göteborgs Universitet
URL: http://hdl.handle.net/2077/67127
► From a clinical standpoint, there are many factors to consider when optimizing the care for people living with HIV (PLWH). With help from clinical guidelines,…
(more)
▼ From a clinical standpoint, there are many factors to consider when optimizing the care for people living with HIV (PLWH). With help from clinical guidelines, most obstacles can be addressed. Expanded knowledge is however in constant demand, from local conditions to universal processes. This thesis emerged from a demand for both clinical and virological data about the effect of antiretroviral treatment (ART) in Sweden. All data were derived from the national InfCareHIV database.
The current goal of ART is to achieve lasting suppression to < 50 HIV RNA copies/mL. Transient episodes of viremia up to 500 copies/mL, so-called viral blips, are not uncommon. We sought to investigate the clinical importance and outcome of this phenomenon. Through two large retrospective studies, Paper I and IV, we concluded that it is more common with blips in PLWH with higher baseline viral load and ART based on boosted Protease Inhibitors (PI). Blip incidence during Integrase Strand Transfer Inhibitors (INSTI) and Non- Nucleoside Reverse Transcriptase Inhibitor-based ART was lower at a similar level. In PLWH who reached HIV RNA suppression after initiating their first ART, blips were relatively common (10–20% of all participants) but not associated with an increased risk of virological failure.
Before the introduction of the INSTI dolutegravir, PLWH with resistance mutations to Nucleoside Reverse Transcriptase Inhibitors were often restricted to PI-based treatment. PIs are characterized by many drug interactions and often tolerability issues. In Paper II, 244 participants with either dolutegravir or traditional PI-based ART were retrospectively studied. Dolutegravir has pharmacological benefits and we concluded that it was an equivalent alternative.
Treatment recommendations are not affected by different levels of baseline viremia. Most clinical studies compare the outcome in participants with higher or lower than 100,000 HIV RNA copies/mL. Considerably higher levels of viremia are sometimes observed. In Paper III, we included 2,956 PLWH of whom 394 (13%) had baseline > 500k HIV RNA copies/mL. We found that participants with that high initial viremia needed longer time to reach viral suppression. Initial treatment with INSTIs was associated with faster viral decline. Higher baseline viral load was not associated with an increased risk of virological failure.
Subjects/Keywords: HIV-1; antiretroviral therapy; transient viremia; viral blip; nucleoside transcriptase inhibitor resistance; dolutegravir; baseline viral load; HIV RNA; virological failure
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❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Sörstedt, E. (2021). Antiretroviral treatment of HIV-1 in Sweden with focus on virological aspects. (Thesis). University of Gothenburg / Göteborgs Universitet. Retrieved from http://hdl.handle.net/2077/67127
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Sörstedt, Erik. “Antiretroviral treatment of HIV-1 in Sweden with focus on virological aspects.” 2021. Thesis, University of Gothenburg / Göteborgs Universitet. Accessed March 07, 2021.
http://hdl.handle.net/2077/67127.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Sörstedt, Erik. “Antiretroviral treatment of HIV-1 in Sweden with focus on virological aspects.” 2021. Web. 07 Mar 2021.
Vancouver:
Sörstedt E. Antiretroviral treatment of HIV-1 in Sweden with focus on virological aspects. [Internet] [Thesis]. University of Gothenburg / Göteborgs Universitet; 2021. [cited 2021 Mar 07].
Available from: http://hdl.handle.net/2077/67127.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Sörstedt E. Antiretroviral treatment of HIV-1 in Sweden with focus on virological aspects. [Thesis]. University of Gothenburg / Göteborgs Universitet; 2021. Available from: http://hdl.handle.net/2077/67127
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Indian Institute of Science
15.
Chakraborty, Kausik.
gp120 Immunogen Design And Characterization.
Degree: PhD, Faculty of Science, 2011, Indian Institute of Science
URL: http://etd.iisc.ac.in/handle/2005/1499
► HIV-1 is the causative agent for AIDS and has been a major focus of research for the past two decades. Though there is a combination…
(more)
▼ HIV-
1 is the causative agent for AIDS and has been a major focus of research for the past two decades. Though there is a combination
therapy in place known as the “Highly Active Anti-Retroviral Therapy” (HAART), its usefulness is confounded by the generation of escape mutants, a host of side effects, and its prohibitive cost. The most useful alternative would be the prevention of infection by vaccination. Vaccine research has been focused on the use of recombinant protein sub-units of the virus or combinations thereof to elicit a neutralizing response against the virus. These approaches have mostly resulted in a failure to generate broadly cross reactive neutralizing response against primary strains of the virus. The work reported herein is aimed at designing a rigidified version of gp120/gp120 derivatives and understanding the scope of the various antigenic regions in gp120 in generating a neutralization response.
Chapter one discusses some general features of the virus and the immune system. The general nature of AIDS, its spread and its immunological characteristics are also described in this chapter.
Chapter two discusses the design and NMR structural analysis of gp120 bridging sheet peptide mimics in methanol and water. The structure of gp120 can be loosely divided into two domains (the outer domain and the inner domain) that are linked together by a discontinuous four stranded antiparallel beta sheet known as the bridging sheet. The bridging sheet is known to overlap with the coreceptor binding site of gp120 and hence is a suitable target for designing virus-entry inhibitors. 17b, a neutralizing antibody isolated from an infected individual, is known to bind to this region of gp120. Our aim in this part of the work was to design a four stranded antiparallel beta sheet, based on the sequence of the bridging sheet, that would contain most of the residues involved in 17b binding. NMR and CD studies confirmed that the peptide was well structured in methanol but the structure was largely lost on addition of aqueous solvent. A small population of the peptide was found to be well-folded in aqueous solution.
Chapter three discusses the design and characterization of a gp120-CD4D12 single chain. It is well known that the conformation of gp120 changes upon binding CD4 to expose cryptic epitopes, known as CD4i epitopes. In this work we report the generation of a single chain gp120-CD4 construct that has the cryptic epitopes exposed. The construct bound to 17b, a conformation specific antibody against the bridging sheet of gp120, a cryptic epitope, as well as a non-covalent complex of gp120:CD4D12. There was also very insignificant secondary structural change in gp120 upon complex formation with CD4D12 as observed by CD spectroscopy. Immunological studies with DNA and protein vaccination in guinea-pigs indicated that though 17b like antibodies are generated after immunization, they did not contribute towards the neutralization of primary isolates of the virus. It was also observed that it was the anti-CD4D12 antibodies…
Advisors/Committee Members: Varadarajan, Raghavan (advisor).
Subjects/Keywords: Human Immunodeficiency Virus (HIV); Immunogenetics; HIV-1 gp120; HIV (Viruses); gp120-CD4D12; gp120-M9; HIV Vaccine Design; gp120; Highly Active Anti-Retroviral Therapy (HAART); Molecular Biology
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❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Chakraborty, K. (2011). gp120 Immunogen Design And Characterization. (Doctoral Dissertation). Indian Institute of Science. Retrieved from http://etd.iisc.ac.in/handle/2005/1499
Chicago Manual of Style (16th Edition):
Chakraborty, Kausik. “gp120 Immunogen Design And Characterization.” 2011. Doctoral Dissertation, Indian Institute of Science. Accessed March 07, 2021.
http://etd.iisc.ac.in/handle/2005/1499.
MLA Handbook (7th Edition):
Chakraborty, Kausik. “gp120 Immunogen Design And Characterization.” 2011. Web. 07 Mar 2021.
Vancouver:
Chakraborty K. gp120 Immunogen Design And Characterization. [Internet] [Doctoral dissertation]. Indian Institute of Science; 2011. [cited 2021 Mar 07].
Available from: http://etd.iisc.ac.in/handle/2005/1499.
Council of Science Editors:
Chakraborty K. gp120 Immunogen Design And Characterization. [Doctoral Dissertation]. Indian Institute of Science; 2011. Available from: http://etd.iisc.ac.in/handle/2005/1499

University of Alberta
16.
Roda, Weston C.
Modeling brain lentiviral infections during antiretroviral
therapy in AIDS.
Degree: MS, Department of Mathematical and Statistical
Sciences, 2016, University of Alberta
URL: https://era.library.ualberta.ca/files/chm50ts112
► Understanding human immunodeficiency-1 (HIV-1) replication and latency in different reservoirs is an ongoing challenge in the care of patients with HIV/AIDS. A mathematical model was…
(more)
▼ Understanding human immunodeficiency-1 (HIV-1)
replication and latency in different reservoirs is an ongoing
challenge in the care of patients with HIV/AIDS. A mathematical
model was created that predicted HIV-1 and simian immunodeficiency
virus (SIV) infection dynamics within the brain during effective
combination antiretroviral therapy (cART). By developing a two
compartment mathematical approach, a predictive model was generated
from existing empiric data. Based on previous reports quantifying
total viral DNA levels in brain from HIV-1 and SIV infections,
estimates of proviral DNA burden were made, which were fit to a
mathematical model predicting viral accrual in brain macrophages
from primary infection. To our knowledge this is the first
mathematical modeling study to quantify HIV-1 and SIV infection
dynamics in the brain. Our modeling study indicates that HIV-1 and
SIV provirus burdens in brain increase slowly over time. Assuming
antiretroviral therapy suppresses HIV-1 infection outside the
brain, an effective antiretroviral therapy could eradicate HIV-1
infection in the brain, albeit over a decade for patients without
neurological complications and over two decades for those with
HAND.
Subjects/Keywords: mathematical model; brain macrophage; human immunodeficiency virus-1; HIV-1; simian immunodeficiency virus; SIV; combination antiretroviral therapy; cART; brain; reservoir; lentiviral
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❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Roda, W. C. (2016). Modeling brain lentiviral infections during antiretroviral
therapy in AIDS. (Masters Thesis). University of Alberta. Retrieved from https://era.library.ualberta.ca/files/chm50ts112
Chicago Manual of Style (16th Edition):
Roda, Weston C. “Modeling brain lentiviral infections during antiretroviral
therapy in AIDS.” 2016. Masters Thesis, University of Alberta. Accessed March 07, 2021.
https://era.library.ualberta.ca/files/chm50ts112.
MLA Handbook (7th Edition):
Roda, Weston C. “Modeling brain lentiviral infections during antiretroviral
therapy in AIDS.” 2016. Web. 07 Mar 2021.
Vancouver:
Roda WC. Modeling brain lentiviral infections during antiretroviral
therapy in AIDS. [Internet] [Masters thesis]. University of Alberta; 2016. [cited 2021 Mar 07].
Available from: https://era.library.ualberta.ca/files/chm50ts112.
Council of Science Editors:
Roda WC. Modeling brain lentiviral infections during antiretroviral
therapy in AIDS. [Masters Thesis]. University of Alberta; 2016. Available from: https://era.library.ualberta.ca/files/chm50ts112

University of KwaZulu-Natal
17.
Naicker, Shamara.
Functional characterization of human immunodeficiency virus type 1 (HIV-1) subtype C transmitted/founder (T/F) viruses long terminal repeat (LTR) variants and association with disease outcome.
Degree: 2020, University of KwaZulu-Natal
URL: https://researchspace.ukzn.ac.za/handle/10413/18605
► Background: The persistence of latent viral reservoirs is a major roadblock to human immunodeficiency virus type 1 (HIV-1) cure development. Latent reservoirs harbour transcriptionally silent…
(more)
▼ Background: The persistence of latent viral reservoirs is a major roadblock to human immunodeficiency virus type
1 (
HIV-
1) cure development. Latent reservoirs harbour transcriptionally silent yet replication competent proviruses. However, the molecular mechanisms that govern
HIV-
1 latency at the transcriptional level is unknown. Therefore, we hypothesize that
HIV-
1 subtype C (
HIV-1C) transmitted/founder (T/F) 5’ long terminal repeat (LTR) genetic variation may affect disease outcome.
Methods: To address this, viral RNA was extracted from plasma samples obtained from 25
HIV-
1 infected patients from the HPP and FRESH acute infection cohorts (QIAamp® Viral RNA Mini Kit, Qiagen, Hilden, Germany). Viral RNA was reverse transcribed to DNA using SuperScript™ III One Step RT-PCR System with Platinum™ Taq DNA Polymerase (Invitrogen, Massachusetts, United States). Nested PCR was performed (Platinum® Taq DNA Polymerase High Fidelity PCR Kit (Invitrogen, Massachusetts, United States) and PCR products cloned into the pGL3 Basic plasmid. LTR/pGL3 recombinant plasmids were sequenced using BigDye Terminator v3.
1 Sequencing Kit (Invitrogen, Massachusetts, United States) to confirm correct sequences. The LTR-pGl3 recombinant plasmids were transfected into Jurkat cells alone or co-transfected with either consensus (wild type) subtype C Tat (conTat) or autologous tat (autoTat) to determine the effect of LTR genetic variation on expression of a luciferase reporter gene.
Results: Interestingly, our data demonstrate that basal transcription activity significantly differs between LTR variants. Specifically, patients harbouring the Sp1 III: G2A mutation demonstrated significantly lower transcription compared to the wild type LTR. Although conTat co-transfection increased the LTR activity for most of the LTR variants, the T/F virus LTR containing the TATA box mutation (TATAA TAAAA) in combination with other LTR mutations was not induced. Interestingly, the transactivation activity of the autologous Tat was variable among patients. Specifically, the TATA box variant was marginally induced. Lastly, we observed that the majority of LTR variants were more responsive to stimulation by PMA as compared to TNF-α, SAHA and prostratin. Interestingly, our data demonstrate that autologous tat induced transcription positively correlated with viral load at transmission (p=0.0134, r=0.66) and at one-year post infection but was not significant (p=0.3905, r=0.26).
Conclusion: These data suggest that the TATAA TAAAA mutation in combination with other LTR mutations may reduce transcription activity. Taken together our data suggest that
HIV-
1 subtype C T/F viruses LTR genetic variation may modulate viral gene transcription and impact disease outcome.
Advisors/Committee Members: Madlala, Paradise Zamokuhle. (advisor).
Subjects/Keywords: Human Immunodeficiency Virus type 1 (HIV-1).; Viruses long terminal repeat (LTR).; Viral RNA.; Combination antiretroviral therapy (cART).
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❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Naicker, S. (2020). Functional characterization of human immunodeficiency virus type 1 (HIV-1) subtype C transmitted/founder (T/F) viruses long terminal repeat (LTR) variants and association with disease outcome. (Thesis). University of KwaZulu-Natal. Retrieved from https://researchspace.ukzn.ac.za/handle/10413/18605
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Naicker, Shamara. “Functional characterization of human immunodeficiency virus type 1 (HIV-1) subtype C transmitted/founder (T/F) viruses long terminal repeat (LTR) variants and association with disease outcome.” 2020. Thesis, University of KwaZulu-Natal. Accessed March 07, 2021.
https://researchspace.ukzn.ac.za/handle/10413/18605.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Naicker, Shamara. “Functional characterization of human immunodeficiency virus type 1 (HIV-1) subtype C transmitted/founder (T/F) viruses long terminal repeat (LTR) variants and association with disease outcome.” 2020. Web. 07 Mar 2021.
Vancouver:
Naicker S. Functional characterization of human immunodeficiency virus type 1 (HIV-1) subtype C transmitted/founder (T/F) viruses long terminal repeat (LTR) variants and association with disease outcome. [Internet] [Thesis]. University of KwaZulu-Natal; 2020. [cited 2021 Mar 07].
Available from: https://researchspace.ukzn.ac.za/handle/10413/18605.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Naicker S. Functional characterization of human immunodeficiency virus type 1 (HIV-1) subtype C transmitted/founder (T/F) viruses long terminal repeat (LTR) variants and association with disease outcome. [Thesis]. University of KwaZulu-Natal; 2020. Available from: https://researchspace.ukzn.ac.za/handle/10413/18605
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of Debrecen
18.
Samatar, Sharmake Husein.
Pharmacological Advances in HIV-1 Therapy
.
Degree: DE – Általános Orvostudományi Kar, University of Debrecen
URL: http://hdl.handle.net/2437/281042
► The thesis is about new and traditional treatments of HIV-1. Investigating the emerging antiretorviral drugs and comparing it with the traditional treatment ways. Reviewing the…
(more)
Subjects/Keywords: HIV-1 therapy;
new advances in HIV-1 therapy;
NNRTI;
NRTI;
PI;
HIV epidemiology;
HIV transmission
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❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Samatar, S. H. (n.d.). Pharmacological Advances in HIV-1 Therapy
. (Thesis). University of Debrecen. Retrieved from http://hdl.handle.net/2437/281042
Note: this citation may be lacking information needed for this citation format:
No year of publication.
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Samatar, Sharmake Husein. “Pharmacological Advances in HIV-1 Therapy
.” Thesis, University of Debrecen. Accessed March 07, 2021.
http://hdl.handle.net/2437/281042.
Note: this citation may be lacking information needed for this citation format:
No year of publication.
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Samatar, Sharmake Husein. “Pharmacological Advances in HIV-1 Therapy
.” Web. 07 Mar 2021.
Note: this citation may be lacking information needed for this citation format:
No year of publication.
Vancouver:
Samatar SH. Pharmacological Advances in HIV-1 Therapy
. [Internet] [Thesis]. University of Debrecen; [cited 2021 Mar 07].
Available from: http://hdl.handle.net/2437/281042.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
No year of publication.
Council of Science Editors:
Samatar SH. Pharmacological Advances in HIV-1 Therapy
. [Thesis]. University of Debrecen; Available from: http://hdl.handle.net/2437/281042
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
No year of publication.
19.
Celina Maria Pereira de Moraes Soares.
Prevalência de resistência transmitida do HIV-1 aos antirretrovirais no Brasil, pré- início de tratamento.
Degree: 2011, Universidade Federal de São Paulo
URL: http://www.bdtd.unifesp.br/tede//tde_busca/arquivo.php?codArquivo=2459
► The selection of resistance mutations to antiretroviral drugs after failure of antiretroviral therapy represents a major challenge for decision-making of new therapeutic regimens in the…
(more)
▼ The selection of resistance mutations to antiretroviral drugs after failure of antiretroviral therapy represents a major challenge for decision-making of new therapeutic regimens in the global pandemic. The high genetic variability of HIV- 1and the selection of resistance mutations trasmitted to patients chronically infected without having participated in the regimen has been the subject of several studies in the world. Resistance patterns are studied mainly in European countries and the United States, wich have majority prevalence of subtype B. However, studies that guide the selection of transmitted mutants to antiretroviral drugs and non-B subtypes, and in their recombinant forms, has increased significantly in the several regions of the world. In Brazil, these studies are conducted sporadically and in different regions of the country and specially in newly infected patients. The high genetic variability of HIV-1 is represented in our country so diverse, with the presence of subtype B, followed by F, and specifically in the South region, the prevalence of subtype C. In addition, coexist the prevalence of recombinant forms, where the principal is the subtype BF, followed by BC. The main objective of this study estimate the characteristics of transmitted resistance mutations to antiretroviral drugs in HIV-1 ol gene, fractions of reverse transcriptase and protease, with mutational analysis of the profile by a population patients chronically infected with HIV-1 and not treated, but with indication of immediate initiation of treatment. We evaluated the patients represented in the demographic regions of Brazil. The national prevalence resulted in 12.1% of transmitted resistance mutations to antiretroviral (intermediate grade 5% to 15%) and 70.8%, 15.5% C, 6.4% F, 4.0% BF and 3.0% BC in the classification of subtypes of HIV-1. In addition, the prevalence of transmitted mutations, the subtypes of HIV-1 and sociodemographic characteristics, laboratory parameters and behavior data in population HIV-1 positive pre-treatment were classified by the cities in five Brazilian regions.
A seleção de mutações de resistência aos medicamentos antirretrovirais pós-falha terapêutica representam um grande desafio para a tomada de decisão de novos esquemas de tratamento na pandemia global. A elevada variabilidade genética do HIV-1 e a seleção de mutações de resistência transmitida a pacientes infectados cronicamente, sem que tenham participado de qualquer esquema terapêutico, tem sido objeto de vários estudos no mundo. Os padrões de resistência são estudados principalmente em países da Europa e Estados Unidos, que apresentam prevalência majoritária do subtipo B. Contudo, estudos que direcionam a seleção de mutações transmitidas aos medicamentos antirretrovirais e em subtipos não-B, assim como em suas formas recombinantes, tem aumentado significativamente em várias regiões do mundo. No Brasil, esses estudos são realizados esporadicamente e em regiões distintas do país e, principalmente, em pacientes recém-infectados. A alta…
Advisors/Committee Members: Shirley Vasconcelos Komninakis, Ester Cerdeira Sabino, Marcos Montani Caseiro, Gilberto Turcato Junior, Jorge Simao do Rosario Casseb, Ricardo Sobhie Diaz.
Subjects/Keywords: HIV-1; Epidemiologia molecular; Resistência transmitida; Pacientes crônicos pré-terapia; DOENCAS INFECCIOSAS E PARASITARIAS; HIV-1; Molecular epidemiology; Transmitted resistance; Chronic patients pre-therapy
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❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Soares, C. M. P. d. M. (2011). Prevalência de resistência transmitida do HIV-1 aos antirretrovirais no Brasil, pré- início de tratamento. (Thesis). Universidade Federal de São Paulo. Retrieved from http://www.bdtd.unifesp.br/tede//tde_busca/arquivo.php?codArquivo=2459
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Soares, Celina Maria Pereira de Moraes. “Prevalência de resistência transmitida do HIV-1 aos antirretrovirais no Brasil, pré- início de tratamento.” 2011. Thesis, Universidade Federal de São Paulo. Accessed March 07, 2021.
http://www.bdtd.unifesp.br/tede//tde_busca/arquivo.php?codArquivo=2459.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Soares, Celina Maria Pereira de Moraes. “Prevalência de resistência transmitida do HIV-1 aos antirretrovirais no Brasil, pré- início de tratamento.” 2011. Web. 07 Mar 2021.
Vancouver:
Soares CMPdM. Prevalência de resistência transmitida do HIV-1 aos antirretrovirais no Brasil, pré- início de tratamento. [Internet] [Thesis]. Universidade Federal de São Paulo; 2011. [cited 2021 Mar 07].
Available from: http://www.bdtd.unifesp.br/tede//tde_busca/arquivo.php?codArquivo=2459.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Soares CMPdM. Prevalência de resistência transmitida do HIV-1 aos antirretrovirais no Brasil, pré- início de tratamento. [Thesis]. Universidade Federal de São Paulo; 2011. Available from: http://www.bdtd.unifesp.br/tede//tde_busca/arquivo.php?codArquivo=2459
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
20.
Basta, Beata.
Nouvelles molécules antivirales ciblant la protéine de la nucléocapside du virus VIH-1 : Novel potent antiviral molecules targeting the nucleocapsid protein of the HIV-1 virus.
Degree: Docteur es, Biophysique, 2012, Université de Strasbourg
URL: http://www.theses.fr/2012STRAJ108
► Étant donnée la séquence hautement conservée de la NC et son rôle crucial dans le cycle viral de VIH-1, les molécules inhibant la NC sont…
(more)
▼ Étant donnée la séquence hautement conservée de la NC et son rôle crucial dans le cycle viral de VIH-1, les molécules inhibant la NC sont susceptibles d'agir comme complément aux thérapies anti-rétrovirales à haute activité (HAART) basées sur des médicaments ciblant les enzymes virales, Des médicaments anti-NC sont ainsi susceptibles d'entraîner un maintien de l'inhibition de la réplication d'un large panel d'isolats VIH-1 incluant des lignées virales résistantes aux médicaments ciblant les enzymes virales. Récemment, dans le cadre du consortium Européen TRIoH, de nouvelles stratégies visant à cibler spécifiquement les propriétés chaperonnes de la NC sur les acides nucléiques ont été développées. Selon une stratégie protégée par un brevet soumis, une série de peptides a été conçue afin d'agir comme compétiteurs de la NC et pouyant ainsi inhiber la réplication du virus. Au sein de cette série, plusieurs peptides ont montré une inhibition efficace des propriétés de déstabilisation des acides nucléiques par la NC. Quatre de ces peptides ont été testés en milieu cellulaire et trois d'entre eux ont montré qu'ils pouvaient inhiber efficacement la réplication du HIV-1 dans les lymphocytes. Dans ce contexte, un premier objectif de cette thèse fût de caractériser avec précision les propriétés de ces peptides. En outre, un objectif supplémentaire fût de caractériser le mécanisme moléculaire vis-à-vis de la NC de petites molécules anti-virales développées par les groupes de D. Daelemans (Leuven) et M. Botta (Sienne).
Due to the highly conserved §equence ofNC and its crucial function during HIV-I life cycle, molecules directedagainst NC are believed to be able to complement the highly active anti-retroviral therapies (HAART) based on drugstargeting the viral enzymes. Anti-NC drugs are thought to provide a sustained replication inhibition of a large panel ofHIV-I isolates including virus strains resistant to drugs targeting viral enąrmes. Recently, within the Europeanconsortium TRIoH, new strategies to specifically target the nucleic acid chaperone properties ofNC were developed.According to a strategy protected by a submitted patent, a series of peptides have been desigrred to act as competitorsforNC and thus, inhibit virus replication. Among this series, several peptides were found to efficiently ińibit therrrrcleic acid destabilization properties ofNC. Four of them have been tested in the cellular context and t}ree out ofthemwere found to efficientĘ ińibit the replication of HIV-I in lymphocytes. In this context, the objective of the thesis wasto characterize in depth the properties ofthese peptides. Moreover, an additional objective was to characterize themolecular mechanism in respect to NC of small antiviral drugs developed by the group of D. Daelemans (Leuven) andM. Botta (Siena).
Advisors/Committee Members: Mély, Yves (thesis director).
Subjects/Keywords: Molécules anti-virales; Thérapies anti-rétrovirales à haute activité; HAART; Protéine de la nucléocapside; HIV-1; Antiviral molecules; HAART therapy; Nucleocapsid protein; HIV-1; 571.4; 616.91
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APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
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to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Basta, B. (2012). Nouvelles molécules antivirales ciblant la protéine de la nucléocapside du virus VIH-1 : Novel potent antiviral molecules targeting the nucleocapsid protein of the HIV-1 virus. (Doctoral Dissertation). Université de Strasbourg. Retrieved from http://www.theses.fr/2012STRAJ108
Chicago Manual of Style (16th Edition):
Basta, Beata. “Nouvelles molécules antivirales ciblant la protéine de la nucléocapside du virus VIH-1 : Novel potent antiviral molecules targeting the nucleocapsid protein of the HIV-1 virus.” 2012. Doctoral Dissertation, Université de Strasbourg. Accessed March 07, 2021.
http://www.theses.fr/2012STRAJ108.
MLA Handbook (7th Edition):
Basta, Beata. “Nouvelles molécules antivirales ciblant la protéine de la nucléocapside du virus VIH-1 : Novel potent antiviral molecules targeting the nucleocapsid protein of the HIV-1 virus.” 2012. Web. 07 Mar 2021.
Vancouver:
Basta B. Nouvelles molécules antivirales ciblant la protéine de la nucléocapside du virus VIH-1 : Novel potent antiviral molecules targeting the nucleocapsid protein of the HIV-1 virus. [Internet] [Doctoral dissertation]. Université de Strasbourg; 2012. [cited 2021 Mar 07].
Available from: http://www.theses.fr/2012STRAJ108.
Council of Science Editors:
Basta B. Nouvelles molécules antivirales ciblant la protéine de la nucléocapside du virus VIH-1 : Novel potent antiviral molecules targeting the nucleocapsid protein of the HIV-1 virus. [Doctoral Dissertation]. Université de Strasbourg; 2012. Available from: http://www.theses.fr/2012STRAJ108
21.
João Ricardo Araujo dos Santos.
Perfil de mutações do vírus da imunodeficiência adquirida tipo 1 associadas à resistência aos antirretrovirais em indivíduos atendidos no município de Catanduva-Noroeste Paulista.
Degree: 2012, Faculdade de Medicina de São José do Rio Preto
URL: http://bdtd.famerp.br//tde_busca/arquivo.php?codArquivo=374
► Introdução: O principal objetivo do uso dos antirretrovirais é retardar a progressão da imunodeficiência e restaurar, tanto quanto possível, a imunidade do indivíduo, aumentando o…
(more)
▼ Introdução: O principal objetivo do uso dos antirretrovirais é retardar a progressão da imunodeficiência e restaurar, tanto quanto possível, a imunidade do indivíduo, aumentando o tempo e a qualidade de vida das pessoas que vivem com HIV-1-AIDS. Os diversos polimorfismos apresentados pelo HIV-1 podem ter implicações na patogênese, na transmissão, no diagnóstico, no tratamento e no desenvolvimento de vacinas que permitam uma profilaxia eficaz. Objetivo: Descrever o perfil de resistência do HIV-1 aos antirretrovirais em pacientes com falha terapêutica em uma unidade de referência no tratamento da AIDS no município de Catanduva, Noroeste Paulista. Métodos: Foram analisados exames de genotipagem de 527 pacientes acompanhados pelo Departamento de Moléstias Infecciosas do Hospital Escola Emílio Carlos, localizado na cidade de Catanduva-SP, solicitados entre janeiro de 2000 e Dezembro de 2010. Todas as sequências do genoma viral (segmentos da TR e PR do gene Pol) foram analisadas nos sites da RENAGENO (MS-Brasil) e reanalizadas utilizando-se o algoritmo da Stanford University, a fim de avaliar a presença de mutações de resistência do HIV-1 através de banco de dados atualizado. Resultados: A maioria dos pacientes analisados pertence ao sexo masculino (58,02%) e à faixa etária entre 40 e 50 anos e já havia sido submetida à TARV. O principal esquema terapêutico utilizado foi composto por três antirretrovirais, sendo prescrito para 62,78% dos pacientes. A mutação 184V foi a mais prevalente (52,7%) entre todas as analisadas. Houve elevada prevalência para as TAM: 215Y, 41L, 67N, 210W, 70R, enquanto 215F e 219Q foram as TAM menos frequentes. Entre as mutações relacionadas à multirresistência, destacamos a presença da mutação 118I em 23,5% dos genomas virais. Dentre as mutações para ITRNN, ressalta-se a elevada prevalência da 103N, encontrada em 28,57% dos casos; a mutação 36I foi a mais frequente dentre as principais da PR. Conclusão: Análises do perfil genômico dos vírus presentes na população estudada mostraram que a presença pontual de uma determinada mutação não implica no aumento da resistência por parte do HIV-1 a determinada droga. Interações entre polimorfismos podem resultar não só em resistência, mas também em suscetibilidade à terapia antirretroviral.
Introduction: The main aim in the use of antiretroviral drugs is delaying the progression of immunodeficiency and restoring, as much as possible, an individuals immunity, increasing the length and quality of life of people living with HIV-1-AIDS. The various polymorphisms presented by HIV-1 may have implications for the pathogenesis, transmission, diagnosis, treatment and development of vaccines which enable an effective prophylaxis. Objective: Describing the resistance profile of HIV-1 to antiretroviral drugs in patients with treatment failure in a reference unit in the treatment of AIDS in the city of Catanduva, Northwestern Region of São Paulo State. Methods: Genotyping tests of 527 patients monitored by the Department of Infectious Diseases belonging to Emilio…
Advisors/Committee Members: Carlos Eugênio Cavasini, José Carlos Lopes, Ricardo Santaella Rosa, Maria Luiza Silva Fazio, Ricardo Luiz Dantas Machado.
Subjects/Keywords: HIV-1; AIDS; Mutação; Terapia antirretroviral; DOENCAS INFECCIOSAS E PARASITARIAS; HIV-1; Síndrome de Imunodeficiência Adquirida; Mutação; HIV-1; AIDS; Mutation; Antiretroviral therapy (ART); VIH-1; Síndrome de Inmunodeficiencia Adquirida; Acquired Immunodeficiency Syndrome; Mutación; Mutation
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❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Santos, J. R. A. d. (2012). Perfil de mutações do vírus da imunodeficiência adquirida tipo 1 associadas à resistência aos antirretrovirais em indivíduos atendidos no município de Catanduva-Noroeste Paulista. (Thesis). Faculdade de Medicina de São José do Rio Preto. Retrieved from http://bdtd.famerp.br//tde_busca/arquivo.php?codArquivo=374
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Santos, João Ricardo Araujo dos. “Perfil de mutações do vírus da imunodeficiência adquirida tipo 1 associadas à resistência aos antirretrovirais em indivíduos atendidos no município de Catanduva-Noroeste Paulista.” 2012. Thesis, Faculdade de Medicina de São José do Rio Preto. Accessed March 07, 2021.
http://bdtd.famerp.br//tde_busca/arquivo.php?codArquivo=374.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Santos, João Ricardo Araujo dos. “Perfil de mutações do vírus da imunodeficiência adquirida tipo 1 associadas à resistência aos antirretrovirais em indivíduos atendidos no município de Catanduva-Noroeste Paulista.” 2012. Web. 07 Mar 2021.
Vancouver:
Santos JRAd. Perfil de mutações do vírus da imunodeficiência adquirida tipo 1 associadas à resistência aos antirretrovirais em indivíduos atendidos no município de Catanduva-Noroeste Paulista. [Internet] [Thesis]. Faculdade de Medicina de São José do Rio Preto; 2012. [cited 2021 Mar 07].
Available from: http://bdtd.famerp.br//tde_busca/arquivo.php?codArquivo=374.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Santos JRAd. Perfil de mutações do vírus da imunodeficiência adquirida tipo 1 associadas à resistência aos antirretrovirais em indivíduos atendidos no município de Catanduva-Noroeste Paulista. [Thesis]. Faculdade de Medicina de São José do Rio Preto; 2012. Available from: http://bdtd.famerp.br//tde_busca/arquivo.php?codArquivo=374
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
22.
Costa, Matthew R.
FC Receptor-Mediated Activities of Env-Specific Monoclonal Antibodies Generated from Human Volunteers Receiving a DNA Prime-Protein Boost HIV Vaccine: A Dissertation.
Degree: Immunology and Microbiology, Medicine, 2016, U of Massachusetts : Med
URL: http://escholarship.umassmed.edu/gsbs_diss/866
► Human immunodeficiency type 1 (HIV-1) is able to elicit broadly potent neutralizing antibodies in a very small subset of individuals only after several years’…
(more)
▼ Human immunodeficiency type
1 (
HIV-
1) is able to elicit broadly potent neutralizing antibodies in a very small subset of individuals only after several years’ infection and as a result, vaccines that elicit these types of antibodies have been difficult to design. The RV144 trial showed that a moderate protection is possible, which may correlate with antibody dependent cellular cytotoxicity (ADCC) activity. Previous studies in the Lu lab demonstrated that in an
HIV-
1 vaccine phase I trial, DP6-001, a polyvalent Env DNA prime-protein boost formulation, could elicit potent and broadly reactive, gp120-specific antibodies with positive neutralization activities along with multiple Fc mediated effector functions. I developed a protocol for the production and analysis of
HIV-
1 Env-specific human monoclonal antibodies (mAbs) isolated from these DP6-001 vaccinees. By utilizing a labeled gp120 bait to isolate Env specific B cells, paired heavy and light chain immunoglobulin (Ig) genes were cloned and allowed for the production of monoclonal antibodies with specificity for gp120. By using this protocol, 13 isolated mAbs from four DP6-001 vaccinees showed broad binding activities to gp120 proteins of diverse subtypes, both autologous and heterologous to vaccine immunogens, with mostly conformational epitopes and a few V3 and C5 specific mAbs. Equally cross-reactive Fc-mediated functional activities, including ADCC and antibody dependent cellular phagocytosis (ADCP), were present with both immune sera and isolated mAbs, confirming the induction of non-neutralizing functional antibodies by the DNA prime- protein boost vaccination. Elicitation of broadly reactive mAbs by vaccination in healthy human volunteers confirms the value of the polyvalent formulation in this
HIV-
1 vaccine design.
Advisors/Committee Members: Shan Lu, M.D., Ph.D..
Subjects/Keywords: HIV-1; HIV Infections; env Gene Products; Human Immunodeficiency Virus; Monoclonal Antibodies; HIV Envelope Protein gp120; Vaccines; Vaccination; AIDS Vaccines; Immunology of Infectious Disease; Immunoprophylaxis and Therapy; Virology; Virus Diseases
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❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Costa, M. R. (2016). FC Receptor-Mediated Activities of Env-Specific Monoclonal Antibodies Generated from Human Volunteers Receiving a DNA Prime-Protein Boost HIV Vaccine: A Dissertation. (Doctoral Dissertation). U of Massachusetts : Med. Retrieved from http://escholarship.umassmed.edu/gsbs_diss/866
Chicago Manual of Style (16th Edition):
Costa, Matthew R. “FC Receptor-Mediated Activities of Env-Specific Monoclonal Antibodies Generated from Human Volunteers Receiving a DNA Prime-Protein Boost HIV Vaccine: A Dissertation.” 2016. Doctoral Dissertation, U of Massachusetts : Med. Accessed March 07, 2021.
http://escholarship.umassmed.edu/gsbs_diss/866.
MLA Handbook (7th Edition):
Costa, Matthew R. “FC Receptor-Mediated Activities of Env-Specific Monoclonal Antibodies Generated from Human Volunteers Receiving a DNA Prime-Protein Boost HIV Vaccine: A Dissertation.” 2016. Web. 07 Mar 2021.
Vancouver:
Costa MR. FC Receptor-Mediated Activities of Env-Specific Monoclonal Antibodies Generated from Human Volunteers Receiving a DNA Prime-Protein Boost HIV Vaccine: A Dissertation. [Internet] [Doctoral dissertation]. U of Massachusetts : Med; 2016. [cited 2021 Mar 07].
Available from: http://escholarship.umassmed.edu/gsbs_diss/866.
Council of Science Editors:
Costa MR. FC Receptor-Mediated Activities of Env-Specific Monoclonal Antibodies Generated from Human Volunteers Receiving a DNA Prime-Protein Boost HIV Vaccine: A Dissertation. [Doctoral Dissertation]. U of Massachusetts : Med; 2016. Available from: http://escholarship.umassmed.edu/gsbs_diss/866

University of Adelaide
23.
Koldej, Rachel Marie.
The development of HIV-1 derived gene transfer technology: optimisation of vector safety, processing and production.
Degree: 2008, University of Adelaide
URL: http://hdl.handle.net/2440/42907
► Vectors derived from Human Immunodeficiency Virus type 1 (HIV-1) are being widely developed for gene therapy applications, principally because they are able to transduce both…
(more)
▼ Vectors derived from Human Immunodeficiency Virus type
1 (
HIV-
1) are being widely developed for gene
therapy applications, principally because they are able to transduce both dividing and non-dividing cells and result in stable, long term gene expression. However, these vectors are difficult to produce in high titres and sufficient volumes for large scale experiments and clinical application. Therefore, an investigation into methods to improve the production of
HIV-
1 derived gene transfer vectors was undertaken.
One factor that limits the production of recombinant virus is the amount of viral genomic RNA available for packaging into virions. Therefore, a transfer vector was modified with the aim of increasing the amount of genomic RNA produced. Substitution of the polyadenylation (pA) signal, mutation splice donor sites and removal of unnecessary sequences were all examined. pA signal readthrough was quantified to determine the effect of these modifications on the rate of pA signal readthrough.
Insertional mutagenesis and vector mobilisation are recognised risk factors with all integrating vectors. Self inactivating (SIN) vectors, which contain a deletion of U3 sequences in the 3’
LTR, demonstrate a reduced rate of mobilisation. Transduction with these vectors results in a provirus containing no viral promoter elements, with transcription of the transgene being
controlled from an internal promoter. However, LTR repair of SIN vectors occurs at an appreciable frequency. Therefore, the extent of this deletion was maximised and the effect on the frequency of the repair examined.
The production of lentiviral gene
therapy vectors by large-scale transient transfection is both time consuming and technically difficult. Therefore, methods to increase the scale of production without compromising virus titre were developed. This resulted in fewer transfections and less handling of the cells when making virus on a large scale (3-4 L). In order to process the virus on this scale in a single day (i.e. 8 hours), new concentration and purification methods were established. The protocol consisted of low speed centrifugation, 0.45 μm filtration, 750 kDa ultrafiltration, 0.8 μm filtration and ultracentrifugation. However, the use of ultracentrifugation means that this protocol is not amenable to further scale up. Therefore, the replacement of the ultracentrifugation step with anion exchange was investigated. A number of different resins and anion exchange devices were investigated, two of which show promise for large scale purification of
HIV-
1 derived gene transfer vectors.
In an ideal world,
HIV-
1 derived gene transfer vectors would be produced using stable packaging cell lines engineered to produce the desired virus. However, previous attempts to produce such a cell line with the desired properties have had limited success and have generally used outdated helper systems. Therefore, in an attempt to combine the efficiency advantages of having a single helper plasmid with the safety advantages of expressing each protein…
Advisors/Committee Members: Anson, Donald Stewart (advisor), Williams, Keryn A. (advisor), School of Paediatrics and Reproductive Health : Paediatrics (school).
Subjects/Keywords: gene therapy; HIV-1; lentiviral vectors; lentivirus purification; stable packaging; cell lines; HIV-1 purification; lentivirus concentration; HIV-1 concentration
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❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Koldej, R. M. (2008). The development of HIV-1 derived gene transfer technology: optimisation of vector safety, processing and production. (Thesis). University of Adelaide. Retrieved from http://hdl.handle.net/2440/42907
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Koldej, Rachel Marie. “The development of HIV-1 derived gene transfer technology: optimisation of vector safety, processing and production.” 2008. Thesis, University of Adelaide. Accessed March 07, 2021.
http://hdl.handle.net/2440/42907.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Koldej, Rachel Marie. “The development of HIV-1 derived gene transfer technology: optimisation of vector safety, processing and production.” 2008. Web. 07 Mar 2021.
Vancouver:
Koldej RM. The development of HIV-1 derived gene transfer technology: optimisation of vector safety, processing and production. [Internet] [Thesis]. University of Adelaide; 2008. [cited 2021 Mar 07].
Available from: http://hdl.handle.net/2440/42907.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Koldej RM. The development of HIV-1 derived gene transfer technology: optimisation of vector safety, processing and production. [Thesis]. University of Adelaide; 2008. Available from: http://hdl.handle.net/2440/42907
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of South Africa
24.
Zhou, Tolybert Munodawafa.
Evaluation of virologic monitoring frequencies on responses to antiretroviral therapy in HIV-1 infected patients
.
Degree: 2017, University of South Africa
URL: http://hdl.handle.net/10500/23812
► The purpose of this study was to assess the impact of virologic monitoring frequencies on treatment failure, adherence to therapy, and the emergence of drug…
(more)
▼ The purpose of this study was to assess the impact of virologic monitoring frequencies on treatment failure, adherence to
therapy, and the emergence of drug resistance in
HIV-
1 infected patients. A quantitative, meta-analysis was conducted to investigate the virologic outcomes of infrequent and frequent Viral Load (VL) testing among patient on combination antiretroviral
therapy (cART). Data was collected through a self-designed data collection form. Two comparison groups emerged being guided by the VL monitoring frequency. In group I, the health outcomes were compared for (≥3 VLs per year) versus (≤2 VLs per year) and (2 VLs per year) versus (≤
1 VLs per year) for group II. Data were analysed using the Cochrane's statistical software, RevMan v5.3. The findings support (2 VLs per year) as the optimal VL monitoring strategy for stable and virologically suppressed patients and there is nothing to be gained by (≥3 VLs per year).
Advisors/Committee Members: Matlakala, M.C (advisor).
Subjects/Keywords: Anti-retroviral (ARV) drugs;
Viral load (VL);
Virologic monitoring frequencies;
Responses to antiretroviral therapy;
HIV-1 infected patients;
Evaluation.
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❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Zhou, T. M. (2017). Evaluation of virologic monitoring frequencies on responses to antiretroviral therapy in HIV-1 infected patients
. (Masters Thesis). University of South Africa. Retrieved from http://hdl.handle.net/10500/23812
Chicago Manual of Style (16th Edition):
Zhou, Tolybert Munodawafa. “Evaluation of virologic monitoring frequencies on responses to antiretroviral therapy in HIV-1 infected patients
.” 2017. Masters Thesis, University of South Africa. Accessed March 07, 2021.
http://hdl.handle.net/10500/23812.
MLA Handbook (7th Edition):
Zhou, Tolybert Munodawafa. “Evaluation of virologic monitoring frequencies on responses to antiretroviral therapy in HIV-1 infected patients
.” 2017. Web. 07 Mar 2021.
Vancouver:
Zhou TM. Evaluation of virologic monitoring frequencies on responses to antiretroviral therapy in HIV-1 infected patients
. [Internet] [Masters thesis]. University of South Africa; 2017. [cited 2021 Mar 07].
Available from: http://hdl.handle.net/10500/23812.
Council of Science Editors:
Zhou TM. Evaluation of virologic monitoring frequencies on responses to antiretroviral therapy in HIV-1 infected patients
. [Masters Thesis]. University of South Africa; 2017. Available from: http://hdl.handle.net/10500/23812

University of New South Wales
25.
Lee, Frederick.
Efficacy and adverse outcomes of combination antiretroviral therapy in HIV-1-infected adults.
Degree: Clinical School - St Vincent's Hospital, 2014, University of New South Wales
URL: http://handle.unsw.edu.au/1959.4/53886
;
https://unsworks.unsw.edu.au/fapi/datastream/unsworks:12596/SOURCE02?view=true
► Current estimates of combination antiretroviral therapy (cART) efficacy are founded upon randomised studies typically of less than two yearsâ duration, and do not mark long-term,…
(more)
▼ Current estimates of combination antiretroviral
therapy (cART) efficacy are founded upon randomised studies typically of less than two yearsâ duration, and do not mark long-term, non-AIDS morbidities (e.g. cardiovascular, renal, and liver disease, diabetes, cancer), which remain more common in
HIV-infected persons and are associated with chronic exposure to some antiretroviral drugs.This thesis reviews existing knowledge of cART efficacy and non-AIDS morbidities, with two broad aims for its original research components: (
1) evaluate the evidence for efficacy and adequacy of harms reporting amongst studies of initial cART; and (2) investigate novel toxicities for the current âPreferredâ antiretrovirals atazanavir, darunavir, and raltegravir.A meta-analysis of initial cART studies showed improved mean efficacy between 1994 and 2010 (43% to 78%), but durability remains a concern, with participant decision and adverse events responsible for treatment interruption in almost 20% of patients. Drug selection (favouring integrase strand transfer inhibitors and tenofovir-emtricitabine) is a key determinant of greater efficacy, as is lower pre-treatment plasma viral load. A second meta-analysis of published initial cART studies showed inadequate harms reporting by published cART studies: deaths, AIDS, serious non-AIDS and serious adverse events were reported by 83%, 53%, 25%, and 42% of studies, respectively â frequencies which remain mostly unchanged over time.In a randomised study of
HIV-negative adults, no difference was found between the post-prandial lipid effects of atazanavir/ritonavir and darunavir/ritonavir, suggesting it is not a mechanism for greater cardiovascular risk. Atazanavir/ritonavir elicited lower post-prandial arterial stiffness, which may contribute to its cardiovascular-neutral risk profile. In contrast, a cross-sectional assessment of cART-experienced patients found raltegravir to be associated with greater prevalence of skeletal muscle toxicity. Proximal myopathy was a newly-identified toxicity seen with raltegravir, but was relatively uncommon (4%).Clinical events remain relevant â and necessary â to providing a true assessment of cART benefits and harms. Recording reasons for why patients elect to interrupt treatment and reporting all clinical harms will improve cART durability. Organ-specific toxicities may not become evident for years post-approval, and are unaccounted for by current methods of determining efficacy. New cART drugs require continuing evaluation for their contribution to long-term harmful outcomes.
Advisors/Committee Members: Carr, Andrew, Clinical School - St Vincent's Hospital, Faculty of Medicine, UNSW, Amin, Janaki, Kirby Institute, Faculty of Medicine, UNSW.
Subjects/Keywords: Antiviral efficacy; Adverse events; Antiretroviral therapy; Cardiovascular risk; HIV-1 infection; Medicine; Serious non-AIDS events
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❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Lee, F. (2014). Efficacy and adverse outcomes of combination antiretroviral therapy in HIV-1-infected adults. (Doctoral Dissertation). University of New South Wales. Retrieved from http://handle.unsw.edu.au/1959.4/53886 ; https://unsworks.unsw.edu.au/fapi/datastream/unsworks:12596/SOURCE02?view=true
Chicago Manual of Style (16th Edition):
Lee, Frederick. “Efficacy and adverse outcomes of combination antiretroviral therapy in HIV-1-infected adults.” 2014. Doctoral Dissertation, University of New South Wales. Accessed March 07, 2021.
http://handle.unsw.edu.au/1959.4/53886 ; https://unsworks.unsw.edu.au/fapi/datastream/unsworks:12596/SOURCE02?view=true.
MLA Handbook (7th Edition):
Lee, Frederick. “Efficacy and adverse outcomes of combination antiretroviral therapy in HIV-1-infected adults.” 2014. Web. 07 Mar 2021.
Vancouver:
Lee F. Efficacy and adverse outcomes of combination antiretroviral therapy in HIV-1-infected adults. [Internet] [Doctoral dissertation]. University of New South Wales; 2014. [cited 2021 Mar 07].
Available from: http://handle.unsw.edu.au/1959.4/53886 ; https://unsworks.unsw.edu.au/fapi/datastream/unsworks:12596/SOURCE02?view=true.
Council of Science Editors:
Lee F. Efficacy and adverse outcomes of combination antiretroviral therapy in HIV-1-infected adults. [Doctoral Dissertation]. University of New South Wales; 2014. Available from: http://handle.unsw.edu.au/1959.4/53886 ; https://unsworks.unsw.edu.au/fapi/datastream/unsworks:12596/SOURCE02?view=true
26.
Mackler, Randi Michelle.
Understanding Prototype Foamy Virus Integrase Site
Selection, Activity, and Stability.
Degree: PhD, Biomedical Sciences, 2018, The Ohio State University
URL: http://rave.ohiolink.edu/etdc/view?acc_num=osu1542306356468134
► HIV is a worldwide pandemic that remains incurable. Recent statistics show that in the United States alone, ~15 per 100,000 people were newly infected with…
(more)
▼ HIV is a worldwide pandemic that remains incurable.
Recent statistics show that in the United States alone, ~15 per
100,000 people were newly infected with
HIV-
1 in one year. The
barrier to a cure is a reservoir of cells with viral DNA stably
integrated into their genome, yet are not killed by the immune
system. The integration step of the retroviral life cycle is
crucial in reservoir formation. Viral DNA integration is catalyzed
by protein integrase (IN). We study
HIV-
1 IN and prototype foamy
virus (PFV) IN. PFV IN is used to model for
HIV-
1 integration, as
HIV-
1 IN inhibitors also block PFV IN activity. This implies that
the two proteins have similar catalytic mechanisms.However, we have
found differences between PFV IN and
HIV-
1 IN function. We
determined that PFV IN could utilize calcium for strand transfer,
unlike
HIV-
1 IN. Additionally, though
HIV-
1 IN has been reported to
rapidly commit to its target DNA, PFV IN does not commit within an
hour. There are likely differences in searching and target capture
mechanisms between the two INs.A benefit to using PFV IN is that it
can be readily assembled with oligomers that mimic viral cDNA ends
to form an intasome complex. The PFV intasome contains a tetramer
of PFV IN and two oligomer DNAs. We found in vitro that these
intasomes aggregate at 37°C. Full-length intasomes aggregate more
than those containing truncated PFV IN outer subunits, particularly
deleting the carboxyl terminal domain (CTD). Aggregation can be
prevented by using high non-physiological salt concentrations or
with addition of small molecule protocatechuic acid (PCA). This
finding is useful for future experiments that require longer
lifetimes of PFV intasomes. Integration into chromatin is not well
understood. Chromatin is comprised of basic units called
nucleosomes. Our goal is to understand how IN chooses its site when
integrating into nucleosomes. We altered either nucleosomes or PFV
IN to understand how changes impact integration activity and site
specificity. Perturbations include using nucleosomes with specific
histone posttranslational modifications (PTMs), altering salt
concentration, and utilizing PFV IN truncation mutants. We
hypothesize major grooves with highly bent DNA not occluded by
histone proteins are the most favored sites. However, our studies
showed that not every distorted and exposed major groove is
favored, suggesting that there is more to PFV IN site
selection.Deleting the CTDs of the outer subunits of the IN
tetramer greatly increases integration efficiency to linear DNA,
but this effect is largely lost with integration into nucleosomes.
Truncated mutant complexes are the most impacted by increasing salt
concentrations, and affinity purification experiments showed that
PFV IN ¿CTD intasomes interact weakly with nucleosomes compared to
wild type. Our data supports the hypothesis that CTDs of PFV IN
directly bind to nucleosomes. The interaction is at least partially
mediated by histone tails. These data will expand knowledge in the
field and will be crucial to development of…
Advisors/Committee Members: Yoder, Kristine (Advisor).
Subjects/Keywords: Biochemistry; Biology; Virology; Biomedical Research; integrase; prototype foamy virus; nucleosome; biochemistry; retrovirus; virus; HIV-1; gene therapy
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APA ·
Chicago ·
MLA ·
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APA (6th Edition):
Mackler, R. M. (2018). Understanding Prototype Foamy Virus Integrase Site
Selection, Activity, and Stability. (Doctoral Dissertation). The Ohio State University. Retrieved from http://rave.ohiolink.edu/etdc/view?acc_num=osu1542306356468134
Chicago Manual of Style (16th Edition):
Mackler, Randi Michelle. “Understanding Prototype Foamy Virus Integrase Site
Selection, Activity, and Stability.” 2018. Doctoral Dissertation, The Ohio State University. Accessed March 07, 2021.
http://rave.ohiolink.edu/etdc/view?acc_num=osu1542306356468134.
MLA Handbook (7th Edition):
Mackler, Randi Michelle. “Understanding Prototype Foamy Virus Integrase Site
Selection, Activity, and Stability.” 2018. Web. 07 Mar 2021.
Vancouver:
Mackler RM. Understanding Prototype Foamy Virus Integrase Site
Selection, Activity, and Stability. [Internet] [Doctoral dissertation]. The Ohio State University; 2018. [cited 2021 Mar 07].
Available from: http://rave.ohiolink.edu/etdc/view?acc_num=osu1542306356468134.
Council of Science Editors:
Mackler RM. Understanding Prototype Foamy Virus Integrase Site
Selection, Activity, and Stability. [Doctoral Dissertation]. The Ohio State University; 2018. Available from: http://rave.ohiolink.edu/etdc/view?acc_num=osu1542306356468134
27.
Coulibaly, Tata Safiatou.
Double approche à la thérapie anti-tumorale à l'aide de vecteurs lentiviraux : Double approach to anti-tumoral therapy with lentiviral vectors.
Degree: Docteur es, Virologie : aspects moléculaires et médicaux, 2017, Université de Strasbourg
URL: http://www.theses.fr/2017STRAJ087
► Le traitement du cancer par thérapie génique nécessite d’une part des gènes suicides efficaces et, d’autre part, l’adressage spécifique de ces gènes aux cellules cancéreuses.…
(more)
▼ Le traitement du cancer par thérapie génique nécessite d’une part des gènes suicides efficaces et, d’autre part, l’adressage spécifique de ces gènes aux cellules cancéreuses. J'ai d'abord caractérisé un nouveau gène suicide dérivé de la désoxycytidine kinase humaine (dCK) : le M36. Comparé à la dCK, le M36 permet une meilleure sensibilisation des certaines cellules cancéreuses aux traitements avec différents chimiothérapeutiques comme la gemcitabine et la cytarabine. Ces résultats sont particulièrement encourageants pour l'élimination des cellules cancéreuses résistantes à ces traitements du fait d’un défaut de la dCK. Dans une deuxième partie, je me suis intéressée à l'adressage spécifique des transgènes aux cellules cancéreuses par les vecteurs lentiviraux. J'ai travaillé à la preuve de concept qu’une enveloppe (Env) VIH modifiée peut permettre un tel ciblage. J'ai généré une Env qui a fortement diminué son tropisme naturel et qui comporte un motif liant le marqueur tumoral modèle HER2.
Cancer gene therapy requires the use of an effective suicide gene and the specific targeting of cancer cells. In my PhD work, I have first characterized a new potential suicide gene derived from human deoxycytidine kinase (dCK): M36. Compared to dCK, M36 improves sensitization of certain cancer cells to treatment with chemotherapeutic compounds as gemcitabine and AraC. These results are particularly encouraging for the elimination of cancer cells resistant to the treatment because of a defect with dCK. In a second part, I have worked at the proof of concept that a modified HIV envelope can allow specific targeting of cancer cells by lentiviral vectors. During this work, I have generated a CD4i envelope with a strongly diminished natural tropism and that carries a motif known to bind the model cell surface cancer marker HER2. This envelope constitutes a good starting material to be improved by evolution in cell culture to obtain specific targeting of HER2+ cells.
Advisors/Committee Members: Negroni, Matteo (thesis director).
Subjects/Keywords: Thérapie génique des cancers; Gène suicide; Enveloppe VIH-1; Ciblage spécifique des cellules cancéreuses; Cancer gene therapy; Suicide gene; HIV-1 envelope; Specific targeting of cancer cells; 572.8; 616.99
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❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Coulibaly, T. S. (2017). Double approche à la thérapie anti-tumorale à l'aide de vecteurs lentiviraux : Double approach to anti-tumoral therapy with lentiviral vectors. (Doctoral Dissertation). Université de Strasbourg. Retrieved from http://www.theses.fr/2017STRAJ087
Chicago Manual of Style (16th Edition):
Coulibaly, Tata Safiatou. “Double approche à la thérapie anti-tumorale à l'aide de vecteurs lentiviraux : Double approach to anti-tumoral therapy with lentiviral vectors.” 2017. Doctoral Dissertation, Université de Strasbourg. Accessed March 07, 2021.
http://www.theses.fr/2017STRAJ087.
MLA Handbook (7th Edition):
Coulibaly, Tata Safiatou. “Double approche à la thérapie anti-tumorale à l'aide de vecteurs lentiviraux : Double approach to anti-tumoral therapy with lentiviral vectors.” 2017. Web. 07 Mar 2021.
Vancouver:
Coulibaly TS. Double approche à la thérapie anti-tumorale à l'aide de vecteurs lentiviraux : Double approach to anti-tumoral therapy with lentiviral vectors. [Internet] [Doctoral dissertation]. Université de Strasbourg; 2017. [cited 2021 Mar 07].
Available from: http://www.theses.fr/2017STRAJ087.
Council of Science Editors:
Coulibaly TS. Double approche à la thérapie anti-tumorale à l'aide de vecteurs lentiviraux : Double approach to anti-tumoral therapy with lentiviral vectors. [Doctoral Dissertation]. Université de Strasbourg; 2017. Available from: http://www.theses.fr/2017STRAJ087

University of Pretoria
28.
Mahasha, Phetole
Walter.
Compartmentalization, adaptive evolution and therapeutic response
of HIV-1 in the gastrointestinal tract (GIT) of African patients
infected with Subtype C: implications for the enhancement of
therapeutic efficacy.
Degree: PhD, Immunology, 2014, University of Pretoria
URL: http://hdl.handle.net/2263/43156
► Background: Due to its continuous exposure to food antigens and microbes, the gastrointestinal tract (GIT) is in a constant state of low level immune activation…
(more)
▼ Background: Due to its continuous exposure to food
antigens and microbes, the gastrointestinal tract (GIT) is in a
constant state of low level immune activation and contains an
abundance of activated CCR5+CD4+ T lymphocytes, the primary target
HIV-
1. As a result, the GIT is a site of intense viral replication
and severe CD4+ T cell depletion, a process that begins during
primary
HIV-
1 infection and continues at a reduced rate during
chronic infection in association with increased production of
pro-inflammatory cytokines, a breakdown in the epithelial barrier,
microbial translocation, systemic immune activation and the
continued recruitment and infection of new target cells.
AntiRetroviral
Therapy (ART) is only partially effective in
reversing these pathogenic changes. Despite the importance of the
GIT in
HIV-
1 pathogenesis, and as a reservoir of persistent virus
during ART, little is known about the diversity of
HIV-
1 in the
GIT, or how different tissues in the GIT respond to ART.
Objectives: Primary objectives of this thesis were to:
1)
characterize the diversity of
HIV-
1 RNA variants in different parts
of the GIT; 2) determine whether there is compartmentalized
evolution of
HIV-
1 RNA variants in the GIT and whether these
variants are likely to have different biological properties; 3)
investigate the impact of ART on immune restoration in the GIT.
Methods: A prospective study of the duodenum, jejunum, ileum and
colon of African AIDS patients with chronic diarrhea and/or weight
loss, sampled before and during 6 months of ART. RNA extracted from
gut biopsies was reverse transcribed and PCR amplified. Env and gag
PCR fragments were cloned, sequenced and subjected to extensive
phylogenetic analysis; pol PCR fragments were analyzed for drug
resistance. CD4+, CD8+ and CD38+CD8+ T cells levels in biopsies
collected at baseline (duodenum, jejunum, ileum and colon) and
after 3 (duodenum) and 6 (duodenum and colon) months of ART were
quantified by flow cytometry and immunohistochemistry, plasma and
tissue VL by the Nuclisens assay.
Results: Viral diversity varied
in different regions of the GIT with env
HIV-
1 RNA variants being
significantly more diverse than gag variants. Gag
HIV-
1 RNA
variants were widely dispersed among all tissue compartments. Some
env variants formed tight monophyletic clusters of closely related
viral quasispecies, especially in the colon, a finding that is
suggestive of compartmentalized viral replication and adaptive
evolution. CD4+ T cell and VL levels were significantly lower,
while CD8+ including activated CD38+CD8+ T cell levels were higher
in the duodenum and jejunum versus the colon. After 6 months of
ART, a significant but incomplete recovery of CD4+ T cells was
observed in the colon but not in the duodenum. Failed restoration
of CD4+ T cells in the duodenum was associated with non-specific
enteritis and CD8+ T cell activation.
Conclusions: These results
advance our understanding of the GIT as a host-pathogen interface
by providing new insights into the diversity, evolution and
dissemination…
Advisors/Committee Members: Cassol, Sharon (advisor), De Oliveira, Tulio (coadvisor).
Subjects/Keywords: Human
immunodeficiency virus-1 (HIV-1);
Gastrointestinal tract; Antiretroviral
therapy (ART); Viral RNA
quasispecies; Genetic
diversity;
UCTD; CD4
reconstitution; Intestine; Africa; Immune
activation
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❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Mahasha, P. (2014). Compartmentalization, adaptive evolution and therapeutic response
of HIV-1 in the gastrointestinal tract (GIT) of African patients
infected with Subtype C: implications for the enhancement of
therapeutic efficacy. (Doctoral Dissertation). University of Pretoria. Retrieved from http://hdl.handle.net/2263/43156
Chicago Manual of Style (16th Edition):
Mahasha, Phetole. “Compartmentalization, adaptive evolution and therapeutic response
of HIV-1 in the gastrointestinal tract (GIT) of African patients
infected with Subtype C: implications for the enhancement of
therapeutic efficacy.” 2014. Doctoral Dissertation, University of Pretoria. Accessed March 07, 2021.
http://hdl.handle.net/2263/43156.
MLA Handbook (7th Edition):
Mahasha, Phetole. “Compartmentalization, adaptive evolution and therapeutic response
of HIV-1 in the gastrointestinal tract (GIT) of African patients
infected with Subtype C: implications for the enhancement of
therapeutic efficacy.” 2014. Web. 07 Mar 2021.
Vancouver:
Mahasha P. Compartmentalization, adaptive evolution and therapeutic response
of HIV-1 in the gastrointestinal tract (GIT) of African patients
infected with Subtype C: implications for the enhancement of
therapeutic efficacy. [Internet] [Doctoral dissertation]. University of Pretoria; 2014. [cited 2021 Mar 07].
Available from: http://hdl.handle.net/2263/43156.
Council of Science Editors:
Mahasha P. Compartmentalization, adaptive evolution and therapeutic response
of HIV-1 in the gastrointestinal tract (GIT) of African patients
infected with Subtype C: implications for the enhancement of
therapeutic efficacy. [Doctoral Dissertation]. University of Pretoria; 2014. Available from: http://hdl.handle.net/2263/43156
29.
Kovalenko, Lesia.
Sélection et caractérisation de molécules ciblant la protéine de la nucléocapside de VIH-1 : Selection and characterization of molecules that target the HIV-1 nucleocapsid protein.
Degree: Docteur es, Biophysique et biologie structurale, 2017, Université de Strasbourg
URL: http://www.theses.fr/2017STRAJ086
► La tri-thérapie utilisée pour le traitement du VIH-1 est efficace mais limitée par l'apparition de résistances. Par conséquent, des cibles virales alternatives sont nécessaires. Une…
(more)
▼ La tri-thérapie utilisée pour le traitement du VIH-1 est efficace mais limitée par l'apparition de résistances. Par conséquent, des cibles virales alternatives sont nécessaires. Une des cibles les plus prometteuses est la protéine nucléocapside (NC), qui est hautement conservée et qui joue un rôle essentiel dans le cycle viral. Dans ce contexte, le projet européen THINPAD a eu pour but de développer des inhibiteurs de la NC en combinant plusieurs approches : criblage virtuel, criblage secondaire in vitro, tests antiviraux et de toxicité. Pour le criblage in vitro, nous avons utilisé le test de déstabilisation de cTAR, hautement spécifique de l’activité chaperonne de NC. Cinq séries de molécules ont été sélectionnées par les premiers criblages et tests antiviraux. Après des études de relation structure-activité, une seule des cinq séries a été poursuivie jusqu’aux tests d'efficacité chez les souris. Les composés de cette série présentent une activité antivirale à des concentrations nanomolaires, mais ne sont pas actifs dans le modèle murin. Les études de mécanisme d'action ont révélés que leur activité antivirale était bien consécutive au ciblage de la NC.
Highly Active Anti-Retroviral Therapy (HAART) is successfully used for HIV-1 treatment, but is hampered by the appearance of drug resistance. Thereby, alternative drug targets are required. One of the most promising target is the nucleocapsid protein (NC), which is highly conserved and plays essential role in HIV life cycle. In this context, the European project THINPAD was organized with the aim to develop NC inhibitors. To fulfil this objective, several approaches were used, including virtual screening, in vitro secondary screening, in cellulo antivirals tests, and toxicity evaluation. For in vitro screening, the specific NC-promoted cTAR destabilization assay was used. Five series of molecules were selected by the first screenings and antiviral tests. After structure-activity relationship studies, only one series was continued until efficacy testing in mice. The compounds of this series exhibit antiviral activity at nanomolar concentrations but are not active in the murine model. The mechanisms of action studies revealed that their antiviral activity was indeed consecutive to the targeting of the NC.
Advisors/Committee Members: Mély, Yves (thesis director), Zaporozhets, Olga (thesis director).
Subjects/Keywords: Thérapie du VIH-1; Résistance aux médicaments; Protéine de la nucléocapside; Inhibiteurs; Criblage; HIV-1 therapy; Drug resistance; Nucleocapsid protein; Inhibitors; Screening; 572.8; 615.7
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❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Kovalenko, L. (2017). Sélection et caractérisation de molécules ciblant la protéine de la nucléocapside de VIH-1 : Selection and characterization of molecules that target the HIV-1 nucleocapsid protein. (Doctoral Dissertation). Université de Strasbourg. Retrieved from http://www.theses.fr/2017STRAJ086
Chicago Manual of Style (16th Edition):
Kovalenko, Lesia. “Sélection et caractérisation de molécules ciblant la protéine de la nucléocapside de VIH-1 : Selection and characterization of molecules that target the HIV-1 nucleocapsid protein.” 2017. Doctoral Dissertation, Université de Strasbourg. Accessed March 07, 2021.
http://www.theses.fr/2017STRAJ086.
MLA Handbook (7th Edition):
Kovalenko, Lesia. “Sélection et caractérisation de molécules ciblant la protéine de la nucléocapside de VIH-1 : Selection and characterization of molecules that target the HIV-1 nucleocapsid protein.” 2017. Web. 07 Mar 2021.
Vancouver:
Kovalenko L. Sélection et caractérisation de molécules ciblant la protéine de la nucléocapside de VIH-1 : Selection and characterization of molecules that target the HIV-1 nucleocapsid protein. [Internet] [Doctoral dissertation]. Université de Strasbourg; 2017. [cited 2021 Mar 07].
Available from: http://www.theses.fr/2017STRAJ086.
Council of Science Editors:
Kovalenko L. Sélection et caractérisation de molécules ciblant la protéine de la nucléocapside de VIH-1 : Selection and characterization of molecules that target the HIV-1 nucleocapsid protein. [Doctoral Dissertation]. Université de Strasbourg; 2017. Available from: http://www.theses.fr/2017STRAJ086
30.
Ibrahim, Karim Yaqub.
Escape transitório da viremia plasmática de HIV-1 e falência virológica em indivíduos sob terapêutica anti-retroviral: incidência e fatores associados.
Degree: PhD, Doenças Infecciosas e Parasitárias, 2010, University of São Paulo
URL: http://www.teses.usp.br/teses/disponiveis/5/5134/tde-04112010-171645/
;
► INTRODUÇÃO: Pacientes em terapia anti-retroviral podem apresentar escapes transitórios de viremia plasmática (blip), porém os preditores desse evento e seu impacto sobre a incidência de…
(more)
▼ INTRODUÇÃO: Pacientes em terapia anti-retroviral podem apresentar escapes transitórios de viremia plasmática (blip), porém os preditores desse evento e seu impacto sobre a incidência de falência virológica são ainda controversos na literatura. Neste estudo de coorte estimou-se a incidência de blip e de falência virológica e investigaram-se possíveis preditores de tais desfechos. Blip foi definido como carga viral superior a 50 cópias/mL com subseqüente supressão da viremia plasmática e falência virológica como duas medidas consecutivas de carga viral plasmática superiores a 50 cópias/mL. Adicionalmente, pesquisou-se, por ocasião desses eventos, a presença de mutações genotípicas de
HIV capazes de conferir resistência aos anti-retrovirais e as concentrações plasmáticas de inibidores não nucleosídicos da transcriptase reversa e inibidores da protease, comparando-as com o relato dos participantes sobre adesão à medicação. MÉTODOS: 350 participantes infectados pelo
HIV (250 homens e 100 mulheres) foram selecionados no Serviço de Extensão ao Atendimento de Pacientes com
HIV/Aids Casa da Aids do Hospital das Clínicas da FMUSP, São Paulo, Brasil. Na admissão ao estudo e trimestralmente, ao longo de 78 semanas, foram coletadas informações sobre dados sóciodemográficos, forma presumida de aquisição do vírus, uso de e adesão a medicações anti-retrovirais, ocorrência de outras comorbidades, bem como uso de álcool e de drogas ilícitas. Investigaram-se fatores potencialmente associados à incidência dos desfechos de interesse, tais como ocorrência de outras doenças, exposição a imunizações e falha na adesão a práticas de sexo mais seguro. Amostras de sangue periférico foram coletadas a cada visita para determinação de carga viral plasmática por RT-PCR ultrassensível, e contagem de linfócitos T CD4+ por citometria de fluxo. Nos indivíduos que apresentaram os desfechos de interesse do estudo, procedeu-se ao seqüenciamento dos genes da transcriptase reversa e da protease de
HIV e à dosagem plasmática dos anti-retrovirais por método de Cromatografia Líquida de Alta Performance. As incidências de blip e falência virológica foram estimadas e os fatores associados a ambos investigados em modelo de regressão logística múltipla. RESULTADOS: As incidências de blip e falência virológica foram 9,4 e 4,2/100 pessoas-ano, respectivamente. Três indivíduos apresentaram falência virológica precedidos por blip. À análise multivariada, a não adesão às praticas de sexo mais seguro no mês precedente se mostrou independentemente associada à ocorrência de blip (OR 24,64, IC 95% 4,40 137,88, p<0,001) e de falência virológica (OR 24,69, IC 95% 4,20 145,18, p<0,001). Adicionalmente, observou-se que a exposição prévia a maior número de esquemas anti-retrovirais foi preditora dos eventos blip (OR
1,82, IC 95%
1,41 2,36, p<0,001) e falência virológica (OR
1,67, IC 95%
1,19 2,35, p=0,003). A ocorrência de blip não se associou ao desenvolvimento posterior de falência virológica. Um maior número de mutações conferidoras de resistência medicamentosa foi…
Advisors/Committee Members: Segurado, Aluisio Augusto Cotrim.
Subjects/Keywords: Antiretroviral therapy; Carga viral; Dosage/Analysis; Dosagem/análises; HIV viral load; HIV-1; HIV-1; Incidence; Incidência; Intermittent viraemia; Mutações; Mutations; Reação em cadeia de polimerase via transcriptase reversa; Reverse transcriptase-polymerase chain reaction; Terapia antiretroviral; Viremia intermitente
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❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Ibrahim, K. Y. (2010). Escape transitório da viremia plasmática de HIV-1 e falência virológica em indivíduos sob terapêutica anti-retroviral: incidência e fatores associados. (Doctoral Dissertation). University of São Paulo. Retrieved from http://www.teses.usp.br/teses/disponiveis/5/5134/tde-04112010-171645/ ;
Chicago Manual of Style (16th Edition):
Ibrahim, Karim Yaqub. “Escape transitório da viremia plasmática de HIV-1 e falência virológica em indivíduos sob terapêutica anti-retroviral: incidência e fatores associados.” 2010. Doctoral Dissertation, University of São Paulo. Accessed March 07, 2021.
http://www.teses.usp.br/teses/disponiveis/5/5134/tde-04112010-171645/ ;.
MLA Handbook (7th Edition):
Ibrahim, Karim Yaqub. “Escape transitório da viremia plasmática de HIV-1 e falência virológica em indivíduos sob terapêutica anti-retroviral: incidência e fatores associados.” 2010. Web. 07 Mar 2021.
Vancouver:
Ibrahim KY. Escape transitório da viremia plasmática de HIV-1 e falência virológica em indivíduos sob terapêutica anti-retroviral: incidência e fatores associados. [Internet] [Doctoral dissertation]. University of São Paulo; 2010. [cited 2021 Mar 07].
Available from: http://www.teses.usp.br/teses/disponiveis/5/5134/tde-04112010-171645/ ;.
Council of Science Editors:
Ibrahim KY. Escape transitório da viremia plasmática de HIV-1 e falência virológica em indivíduos sob terapêutica anti-retroviral: incidência e fatores associados. [Doctoral Dissertation]. University of São Paulo; 2010. Available from: http://www.teses.usp.br/teses/disponiveis/5/5134/tde-04112010-171645/ ;
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