subject:(NRTI)

Universitat de Valencia

1. Pablo Bernal, Carmen de. Efectos proinflamatorios de los fármacos antirretrovirales inhibidores de la transcriptasa inversa análogos de nucleósido in vitro e in vivo .

Degree: 2013, Universitat de Valencia

URL: http://hdl.handle.net/10550/29238

► Los inhibidores de la transcriptasa inversa análogos de nucleós(t)ido (ITIAN) son una familia de fármacos empleados en el tratamiento de la infección por el virus… (more)

▼ Los inhibidores de la transcriptasa inversa análogos de nucleós(t)ido (ITIAN) son una familia de fármacos empleados en el tratamiento de la infección por el virus de la inmunodeficiencia humana (VIH). Este grupo de antirretrovirales está presente en todas las opciones terapéuticas en combinación con fármacos antirretrovirales de otras familias. La administración de estos compuestos, en particular de abacavir (ABC) y didanosina (ddI), se ha asociado con la aparición de efectos adversos a nivel cardiovascular; sin embargo los mecanismos responsables permanecen sin esclarecer. Empleando modelos in vitro e in vivo, hemos evaluado los efectos de concentraciones clínicamente relevantes de estos antirretrovirales sobre la interacción leucocito-endotelio, la cual es el primer paso en la génesis de las enfermedades cardiovasculares con componente inflamatorio tales como infarto de miocardio, aterosclerosis y trombosis. ABC (fármaco más utilizado de esta familia y análogo de purina), indujo la interacción de leucocitos con el endotelio (venoso y arterial) in vitro e in vivo así como un incremento en la expresión de la molécula de adhesión leucocitaria Mac-1 (CD11b/CD18) en neutrófilos y monocitos tanto humanos como de rata. Aunque la expresión de ICAM-1 no se vio modificada por este fármaco, la acumulación leucocitaria inducida por ABC se debe a la interacción Mac-1/ICAM-1, esto se hace evidente por el hecho de que anticuerpos bloqueantes frente a estas moléculas previnieron los diferentes parámetros leucocitarios. Los estudios en los que cada tipo celular (endotelio o leucocitos) fue tratado individualmente indican que el endotelio también posee un papel importante en esta respuesta. Además, a nivel endotelial, ABC promueve la producción de ERO, así como la translocación de NF-κB al núcleo y la pérdida citosólica de su inhibidor IκB-α. Nuestros estudios mostraron una relación estructura-actividad debido al modo en el que los diferentes antirretrovirales actúan: Así, ddI (análogo de purina) reprodujo los efectos tóxicos de ABC, mientras que los análogos de pirimidina lamivudina (3TC), zidovudina (ZDV) y emtricitabina (FTC) o el análogo de nucleótido tenofovir (TDF) no produjeron cambios significativos en ninguno de los parámetros evaluados. Esto sugiere que ABC y ddI están afectando a la ruta de señalización purinérgica y que el ATP está implicado en estos efectos. De este modo, ABC causó tanto un incremento en los niveles de ATP intracelular como una reducción de la expresión de CD73 (enzima responsable de la degradación del ATP) tanto a nivel endotelial como leucocitario. Además, comprobamos el papel del ATP a través de sus receptores P2X7 en el reclutamiento leucocitario inducido por este ITIAN. Por último, la combinación terapéutica ABC/3TC produce el mismo efecto proinflamatorio que ABC. Sin embargo, la alternativa terapéutica FTC/TDF no promueve dichos efectos. En conclusión, el presente trabajo describe el mecanismo proinflamatorio por el cual los ITIAN análogos de purina y más concretamente, ABC, inducen la… Advisors/Committee Members: Esplugues Mota, Juan Vicente (advisor).

Subjects/Keywords: acumulación leucocitaria; cardiovascular; farmacología; inflamación; NRTI; antirretrovirales

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Pablo Bernal, C. d. (2013). Efectos proinflamatorios de los fármacos antirretrovirales inhibidores de la transcriptasa inversa análogos de nucleósido in vitro e in vivo . (Doctoral Dissertation). Universitat de Valencia. Retrieved from http://hdl.handle.net/10550/29238

Chicago Manual of Style (16^th Edition):

Pablo Bernal, Carmen de. “Efectos proinflamatorios de los fármacos antirretrovirales inhibidores de la transcriptasa inversa análogos de nucleósido in vitro e in vivo .” 2013. Doctoral Dissertation, Universitat de Valencia. Accessed January 22, 2021. http://hdl.handle.net/10550/29238.

MLA Handbook (7^th Edition):

Pablo Bernal, Carmen de. “Efectos proinflamatorios de los fármacos antirretrovirales inhibidores de la transcriptasa inversa análogos de nucleósido in vitro e in vivo .” 2013. Web. 22 Jan 2021.

Vancouver:

Pablo Bernal Cd. Efectos proinflamatorios de los fármacos antirretrovirales inhibidores de la transcriptasa inversa análogos de nucleósido in vitro e in vivo . [Internet] [Doctoral dissertation]. Universitat de Valencia; 2013. [cited 2021 Jan 22]. Available from: http://hdl.handle.net/10550/29238.

Council of Science Editors:

Pablo Bernal Cd. Efectos proinflamatorios de los fármacos antirretrovirales inhibidores de la transcriptasa inversa análogos de nucleósido in vitro e in vivo . [Doctoral Dissertation]. Universitat de Valencia; 2013. Available from: http://hdl.handle.net/10550/29238

Vanderbilt University

2. Song, Zhuo. Stochastic modeling of mitochondrial polymerase gamma replication and novel algorithms to enrich rare disease alleles and detect tumor somatic mutations in deep sequencing data.

Degree: PhD, Human Genetics, 2012, Vanderbilt University

URL: http://hdl.handle.net/1803/10702

► The activity of polymerase ã (pol ã) is complicated. To understand how its kinetics values affect the final function of the pol ã, I created… (more)

Subjects/Keywords: tumor somatic mutations; targeted sequencing; NRTI; polymerase gamma; mtDNA replication

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APA (6^th Edition):

Song, Z. (2012). Stochastic modeling of mitochondrial polymerase gamma replication and novel algorithms to enrich rare disease alleles and detect tumor somatic mutations in deep sequencing data. (Doctoral Dissertation). Vanderbilt University. Retrieved from http://hdl.handle.net/1803/10702

Chicago Manual of Style (16^th Edition):

Song, Zhuo. “Stochastic modeling of mitochondrial polymerase gamma replication and novel algorithms to enrich rare disease alleles and detect tumor somatic mutations in deep sequencing data.” 2012. Doctoral Dissertation, Vanderbilt University. Accessed January 22, 2021. http://hdl.handle.net/1803/10702.

MLA Handbook (7^th Edition):

Song, Zhuo. “Stochastic modeling of mitochondrial polymerase gamma replication and novel algorithms to enrich rare disease alleles and detect tumor somatic mutations in deep sequencing data.” 2012. Web. 22 Jan 2021.

Vancouver:

Song Z. Stochastic modeling of mitochondrial polymerase gamma replication and novel algorithms to enrich rare disease alleles and detect tumor somatic mutations in deep sequencing data. [Internet] [Doctoral dissertation]. Vanderbilt University; 2012. [cited 2021 Jan 22]. Available from: http://hdl.handle.net/1803/10702.

Council of Science Editors:

Song Z. Stochastic modeling of mitochondrial polymerase gamma replication and novel algorithms to enrich rare disease alleles and detect tumor somatic mutations in deep sequencing data. [Doctoral Dissertation]. Vanderbilt University; 2012. Available from: http://hdl.handle.net/1803/10702

3. Simu, Elin. Abakavir och lamivudin i kombination med efavirenz eller atazanavir vid behandling av HIV. : En jämförande litteraturstudie om effekt och säkerhet.

Degree: Pharmacology, 2016, Umeå University

URL: http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-119702

► Introduktion Under början av 1980-talet uppmärksammades ovanliga tumörer och infektioner hos unga män som vanligtvis drabbar personer med nedsatt immunförsvar. Forskargrupper i Frankrike och… (more)

▼ Introduktion Under början av 1980-talet uppmärksammades ovanliga tumörer och infektioner hos unga män som vanligtvis drabbar personer med nedsatt immunförsvar. Forskargrupper i Frankrike och USA upptäckte 1983 och 1984 ett nytt virus som fick namnet humant immunbrist virus (HIV). En infektion av HIV fortlöper under många år asymtomatiskt och det är först när immunförsvaret är försvagat som symtom börjar märkas. Första läkemedlet som godkändes för att behandla HIV presenterades 1987 och dödligheten i följdsjukdomen Acquired Immunodeficiency Syndrome (AIDS) minskade drastiskt. Under 1996 infördes en ny behandling i form av kombinationer av tre eller fler läkemedel, som kom att kallas antiretroviral terapi (ART). Syfte Syftet med denna litteraturstudie är att ta reda på om det finns någon skillnad i effekt och säkerhet för ART-kombinationerna abakavir-lamivudin-atazanavir/r (ABC+3TC+ATV/r) och abakavir-lamivudin-efavirenz (ABC+3TC+EFV) som rekommenderas till tidigare obehandlade HIV-patienter. Metod Denna litteraturstudie baseras på nio originalartiklar hämtade från databasen PubMed mellan 19 januari och 7 februari 2016 med sökorden abacavir, lamivudine, atazanavir, efavirenz och efficacy, med begränsningarna english, clinical trial, adult: 19+ years. Antalet träffar sorterades utifrån inklusions- och exklusionskriterierna, att studierna undersökt effekt och säkerhet hos båda kombinationerna ABC+3TC+ATV/r och ABC+3TC+EFV i första hand eller mot andra kombinationer eller i monoterapi i andra hand, studierna ska ha pågått i minst 48 veckor och deltagarna ska ha varit 16 år eller äldre. Resultat och diskussion Nio studier uppfyllde inklusionskriterierna, åtta av dem var randomiserade. Fem av studierna jämförde båda kombinationerna och ytterligare fyra studier inkluderades som studerat en av kombinationerna mot andra kombinationer eller i monoterapi.Studierna påvisade ingen statistisk signifikant skillnad mellan kombinationerna. Antalet patienter som uppnått virushalt under gränsvärdet 50 kopior/ml var i åtta av nio studier fler än 70 %. Biverkningarna redovisades på olika sätt hos studierna, några av dem visade vilka som förekom mest och andra på enstaka metaboliska förändringar.Att studierna inte kunnat påvisa någon signifikant skillnad i effekt eller säkerhet kan vara en faktor som gjort att de valts till förstahandsval för patienter som tidigare inte behandlats med ART. Endast fem studier hade jämfört båda kombinationerna vilket gjorde att studier som jämfört en av kombinationer mot andra kombinationer eller i monoterapi inkluderats för att kunna jämföra effekten hos ART-kombinationerna. Säkerheten hos studierna redovisades på olika sätt vilket gjort att en jämförelse mellan preparatens biverkningar och tolerans varit svår att göra. Slutsats Ingen statistisk signifikant skillnad i effekt och säkerhet mellan kombinationerna har kunnat visas. Fler än 70 % av patienterna uppnådde virushalt <50 kopior/ml efter 48 veckors behandling. Behandlingen tolererades av de…

Subjects/Keywords: HIV; ART; atazanavir/r; efavirenz; NRTI; Pharmaceutical Sciences; Farmaceutiska vetenskaper

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Simu, E. (2016). Abakavir och lamivudin i kombination med efavirenz eller atazanavir vid behandling av HIV. : En jämförande litteraturstudie om effekt och säkerhet. (Thesis). Umeå University. Retrieved from http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-119702

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Simu, Elin. “Abakavir och lamivudin i kombination med efavirenz eller atazanavir vid behandling av HIV. : En jämförande litteraturstudie om effekt och säkerhet.” 2016. Thesis, Umeå University. Accessed January 22, 2021. http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-119702.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Simu, Elin. “Abakavir och lamivudin i kombination med efavirenz eller atazanavir vid behandling av HIV. : En jämförande litteraturstudie om effekt och säkerhet.” 2016. Web. 22 Jan 2021.

Vancouver:

Simu E. Abakavir och lamivudin i kombination med efavirenz eller atazanavir vid behandling av HIV. : En jämförande litteraturstudie om effekt och säkerhet. [Internet] [Thesis]. Umeå University; 2016. [cited 2021 Jan 22]. Available from: http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-119702.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Simu E. Abakavir och lamivudin i kombination med efavirenz eller atazanavir vid behandling av HIV. : En jämförande litteraturstudie om effekt och säkerhet. [Thesis]. Umeå University; 2016. Available from: http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-119702

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

4. Tada, Kohei. Abacavir, an anti-HIV-1 drug, targets TDP1-deficient adult T cell leukemia : 抗HIV薬アバカビルは、TDP1が欠損している成人T細胞白血病を標的とする.

Degree: 博士(医学), 2015, Kyoto University / 京都大学

URL: http://hdl.handle.net/2433/202797 ; http://dx.doi.org/10.14989/doctor.k19363

新制・課程博士

甲第19363号

医博第4040号

Subjects/Keywords: Adult T cell leukemia; Abacavir; TDP1; NRTI; chemotherapy

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Tada, K. (2015). Abacavir, an anti-HIV-1 drug, targets TDP1-deficient adult T cell leukemia : 抗HIV薬アバカビルは、TDP1が欠損している成人T細胞白血病を標的とする. (Thesis). Kyoto University / 京都大学. Retrieved from http://hdl.handle.net/2433/202797 ; http://dx.doi.org/10.14989/doctor.k19363

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Tada, Kohei. “Abacavir, an anti-HIV-1 drug, targets TDP1-deficient adult T cell leukemia : 抗HIV薬アバカビルは、TDP1が欠損している成人T細胞白血病を標的とする.” 2015. Thesis, Kyoto University / 京都大学. Accessed January 22, 2021. http://hdl.handle.net/2433/202797 ; http://dx.doi.org/10.14989/doctor.k19363.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Tada, Kohei. “Abacavir, an anti-HIV-1 drug, targets TDP1-deficient adult T cell leukemia : 抗HIV薬アバカビルは、TDP1が欠損している成人T細胞白血病を標的とする.” 2015. Web. 22 Jan 2021.

Vancouver:

Tada K. Abacavir, an anti-HIV-1 drug, targets TDP1-deficient adult T cell leukemia : 抗HIV薬アバカビルは、TDP1が欠損している成人T細胞白血病を標的とする. [Internet] [Thesis]. Kyoto University / 京都大学; 2015. [cited 2021 Jan 22]. Available from: http://hdl.handle.net/2433/202797 ; http://dx.doi.org/10.14989/doctor.k19363.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Tada K. Abacavir, an anti-HIV-1 drug, targets TDP1-deficient adult T cell leukemia : 抗HIV薬アバカビルは、TDP1が欠損している成人T細胞白血病を標的とする. [Thesis]. Kyoto University / 京都大学; 2015. Available from: http://hdl.handle.net/2433/202797 ; http://dx.doi.org/10.14989/doctor.k19363

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

5. Tada, Kohei. Abacavir, an anti-HIV-1 drug, targets TDP1-deficient adult T cell leukemia .

Degree: 2015, Kyoto University

URL: http://hdl.handle.net/2433/202797

Subjects/Keywords: Adult T cell leukemia; Abacavir; TDP1; NRTI; chemotherapy

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Tada, K. (2015). Abacavir, an anti-HIV-1 drug, targets TDP1-deficient adult T cell leukemia . (Thesis). Kyoto University. Retrieved from http://hdl.handle.net/2433/202797

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Tada, Kohei. “Abacavir, an anti-HIV-1 drug, targets TDP1-deficient adult T cell leukemia .” 2015. Thesis, Kyoto University. Accessed January 22, 2021. http://hdl.handle.net/2433/202797.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Tada, Kohei. “Abacavir, an anti-HIV-1 drug, targets TDP1-deficient adult T cell leukemia .” 2015. Web. 22 Jan 2021.

Vancouver:

Tada K. Abacavir, an anti-HIV-1 drug, targets TDP1-deficient adult T cell leukemia . [Internet] [Thesis]. Kyoto University; 2015. [cited 2021 Jan 22]. Available from: http://hdl.handle.net/2433/202797.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Tada K. Abacavir, an anti-HIV-1 drug, targets TDP1-deficient adult T cell leukemia . [Thesis]. Kyoto University; 2015. Available from: http://hdl.handle.net/2433/202797

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of Georgia

6. Blue, Shawn Kendale. Pharmacokinetics of anti-HIV agents in rodents.

Degree: 2014, University of Georgia

URL: http://hdl.handle.net/10724/26575

► The treatment of HIV/AIDS is one of, if not, the most challenging medical enigmas of the 20th and 21st centuries. At the time of its… (more)

▼ The treatment of HIV/AIDS is one of, if not, the most challenging medical enigmas of the 20th and 21st centuries. At the time of its discovery, HIV patients were predominantly homosexual White males in America. The demographics have changed drastically over the past two decades. Now women make up nearly 50% of global HIV/AIDS patients. The current feminization of HIV demographics has led to another obstacle, mother to child transmission (MTCT). These statistics, coupled with the fact that vertical transmission is the largest factor in the number of newly diagnosed juvenile HIV/AIDS patients, create a need to optimize treatment of HIV positive pregnant women, to reduce vertical transmission of HIV. It has been shown that administration of anti-HIV medications during pregnancy, delivery and to the infant after birth greatly reduces the risk of vertical transmission. Understanding the pharmacokinetics of HIV/AIDS medications alone and in combination during pregnancy is necessary in the development of more effective methods of vertical transmission prophylaxis. Using a pregnant rat model, we have developed analytical methods and investigated the pharmacokinetics and placental transport of anti-HIV drugs alone and in combination. These studies allowed us to determine and understand any possible interactions between drugs in combination. Studies were performed on timed-pregnant Sprague-Dawley rats and pharmacokinetic analysis was performed using WinNonlin. While current methods of treating HIV/AIDS patients have been highly successful, the chance of viral mutations and resistance to Anti-Retroviral Therapy often occurs. In order to combat the resistance of reverse transcriptase inhibitors (NRTI and NNRTI) and protease inhibitors, scientists have continually searched for additional targets on HIV. For instance, integrase inhibitors, block the action of integrase, a viral enzyme, which integrates HIV DNA into the target cells. We have determined the pharmacokinetic profile of an investigational integrase inhibitor. In vivo animal studies were being performed on male Sprague-Dawley rats and female PXR-KO and hPXR transgenic mice and pharmacokinetic analysis was performed using WinNonlin.

Subjects/Keywords: HIV; Pharmacokinetics; Stavudine; Lamivudine; D4T; DDC; Placental Transport; NRTI; Nucleoside Reverse Transcriptase Inhibitors; HPLC; Antiviral Drugs; Integrase Inhibitors

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Blue, S. K. (2014). Pharmacokinetics of anti-HIV agents in rodents. (Thesis). University of Georgia. Retrieved from http://hdl.handle.net/10724/26575

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Blue, Shawn Kendale. “Pharmacokinetics of anti-HIV agents in rodents.” 2014. Thesis, University of Georgia. Accessed January 22, 2021. http://hdl.handle.net/10724/26575.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Blue, Shawn Kendale. “Pharmacokinetics of anti-HIV agents in rodents.” 2014. Web. 22 Jan 2021.

Vancouver:

Blue SK. Pharmacokinetics of anti-HIV agents in rodents. [Internet] [Thesis]. University of Georgia; 2014. [cited 2021 Jan 22]. Available from: http://hdl.handle.net/10724/26575.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Blue SK. Pharmacokinetics of anti-HIV agents in rodents. [Thesis]. University of Georgia; 2014. Available from: http://hdl.handle.net/10724/26575

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of Debrecen

7. 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 (6^th 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 (16^th Edition):

Samatar, Sharmake Husein. “Pharmacological Advances in HIV-1 Therapy .” Thesis, University of Debrecen. Accessed January 22, 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 (7^th Edition):

Samatar, Sharmake Husein. “Pharmacological Advances in HIV-1 Therapy .” Web. 22 Jan 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 Jan 22]. 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.

8. Wang, Ruibin. The impact of tenofovir disoproxil fumarate on estimated glomerular filtration rate change and progression to end-stage renal disease among HIV-infected adults in North America.

Degree: 2015, Johns Hopkins University

URL: http://jhir.library.jhu.edu/handle/1774.2/38064

► Background: Tenofovir disoproxil fumarate (TDF) was associated with an increased risk of renal toxicity, resulting in proximal tubular dysfunction, proteinuria, and chronic kidney disease (CKD).… (more)

▼ Background: Tenofovir disoproxil fumarate (TDF) was associated with an increased risk of renal toxicity, resulting in proximal tubular dysfunction, proteinuria, and chronic kidney disease (CKD). However, TDF-related nephrotoxicity has not been studied in the context of end-state renal disease (ESRD). We hypothesized that TDF-induced toxicity mainly affected a subset of susceptible HIV-infected patients that led to faster progression to ESRD. Methods: Data was extracted from 12 clinical cohorts under the North American AIDS Cohort Collaboration for Research and Design study that carried out systematic ESRD validation from January 2000 to December 2009. Piece-wise log-linear mixed effects models were used to compare and contrast estimated glomerular filtration rate (eGFR) trajectories in TDF and other nucleoside reverse transcriptase inhibitor (NRTI) therapy groups. A nested design was employed to identify risk factors associated with increased ESRD risk after TDF exposure. Results: Among the 19,653 patients, over 20% of high-risk individuals received less than two serum creatinine-based assessments of kidney function per year. For TDF users with baseline eGFR≥90, 60-89.9 and 45-59.9 mL/min/1.73m2, the annualized eGFR change decreased at -10.1% (p<-0.001), -9.9% (p<-0.001) and -27.2% (p<-0.001), respectively during the first 6 months after therapy initiation. In contrast, eGFR decreased at a slower rate or stabilized among alternative NRTI initiators during this period at rates of -5.9% (p<0.001), 0.7% (p=0.596) and 9.8% (p=0.027) for the same eGFR categories. For patients with baseline eGFR in ranges of 30-44.9 and <30 mL/min/1.73m2, eGFR change was non-significant at -14.0% (p=0.068) and -9.3% (p=0.617) per year, respectively among TDF initiators, whereas among alternative NRTI users, eGFR declined at -27.7% (p<0.001) and -31.2% (p<0.001) per year. Among TDF-exposed patients, black race was independently associated with 3.4 [95% CI: 1.2-9.6] times higher ESRD risk. Conclusion: Insufficient screening and monitoring of kidney function remains as an issue for clinical care of kidney diseases among HIV-infected patients. TDF-based therapies are associated with higher ESRD risks. TDF-induced toxicity mainly affects a small subset of susceptible individuals. Advisors/Committee Members: Abraham, Alison G (advisor).

Subjects/Keywords: HIV-infection; Tenofovir disoproxil fumarate (TDF); Nucleoside reverse transcriptase inhibitor (NRTI); End-stage renal Disease (ESRD); Glomerular filtration rate (GFR)

…active research. Tenofovir disoproxil fumartate (TDF) is a member of the NRTI class… …of TDF or alternative NRTI therapy initiation. In addition, to assess the impact of TDF… …care in these 12 cohorts and initiated a TDF or alternative NRTI-containing therapy between… …alternative NRTI-containing therapy was defined as any HAART regimen containing one or more of the… …alternative NRTI-containing therapy (defined as baseline) to the onset of ESRD, death…

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APA (6^th Edition):

Wang, R. (2015). The impact of tenofovir disoproxil fumarate on estimated glomerular filtration rate change and progression to end-stage renal disease among HIV-infected adults in North America. (Thesis). Johns Hopkins University. Retrieved from http://jhir.library.jhu.edu/handle/1774.2/38064

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Wang, Ruibin. “The impact of tenofovir disoproxil fumarate on estimated glomerular filtration rate change and progression to end-stage renal disease among HIV-infected adults in North America.” 2015. Thesis, Johns Hopkins University. Accessed January 22, 2021. http://jhir.library.jhu.edu/handle/1774.2/38064.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Wang, Ruibin. “The impact of tenofovir disoproxil fumarate on estimated glomerular filtration rate change and progression to end-stage renal disease among HIV-infected adults in North America.” 2015. Web. 22 Jan 2021.

Vancouver:

Wang R. The impact of tenofovir disoproxil fumarate on estimated glomerular filtration rate change and progression to end-stage renal disease among HIV-infected adults in North America. [Internet] [Thesis]. Johns Hopkins University; 2015. [cited 2021 Jan 22]. Available from: http://jhir.library.jhu.edu/handle/1774.2/38064.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Wang R. The impact of tenofovir disoproxil fumarate on estimated glomerular filtration rate change and progression to end-stage renal disease among HIV-infected adults in North America. [Thesis]. Johns Hopkins University; 2015. Available from: http://jhir.library.jhu.edu/handle/1774.2/38064

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of Southern California

9. Bi, Lucun. Intracellular drug-drug interaction between nucleoside analogs leads to early virologic failure in HIV patients receiving triple nucleoside combinations of tenofovir, lamivudine and abacavir or didanosine.

Degree: PhD, Pharmaceutical Sciences, 2008, University of Southern California

URL: http://digitallibrary.usc.edu/cdm/compoundobject/collection/p15799coll127/id/47592/rec/3609

► High level of virologic failure was observed in HIV patients receiving combinations of tenofovir (TFV), lamivudine (3TC) combined with either abacavir (ABC) or didanosine (ddI).… (more)

▼ High level of virologic failure was observed in HIV patients receiving combinations of tenofovir (TFV), lamivudine (3TC) combined with either abacavir (ABC) or didanosine (ddI). To investigate the pharmacologic mechanisms involve with the virologic failures, a comprehensive study was undertaken to evaluate the intracellular concentration of the active moiety (ddNTP) of these respective nucleoside analogs.; Triple nucleoside combinations were tested at physiological concentrations revealed reductions of 5 to 33% of the respective ddNTP. In vitro studies evaluating TFV and ABC in a concentration dependent manner showed a reduction of 40% and 30% in intracellular CBV-TP and TFV-DP. Similar findings were demonstrated with TFV and ddI, where 40% and 25% reduction in ddATP and TFV-DP, respectively, was detected. The level of dATP and dGTP, endogenous nucleotides, were increased by 2.4- and 2.7-fold, respectively, when cells were treated with 20 µM TFV, which can dilute the effect of ddNTP.; The expression of MRP2 and MRP4 were increased in cells serially passaged in either ABC or TFV, which correlated with cellular viability in the presence of high concentrations of nucleosides. Moreover, these cells had significantly lower level of ddNTP accumulation as compared to the wild type counterparts.; A clinical study was undertaken to evaluate whether the in vitro findings were also observed in humans. The combination of ABC and TDF resulted in a 2-fold increase in intracellular TFV-DP in patients receiving the combination of ABC and TFV as compared to TDF alone. Increases in TFV-DP may be attributed to higher plasma level of TFV, which was detected in the second phase of this study. A 4-fold increase in CBV-TP was detected three of nine patients, while the other six (6/9) had a 41% reduction. The degree of CBV-TP reduction is consistent with what is seen in vitro.; These findings suggest that cellular adaptive are critical in reducing intracellular levels of nucleoside analogs and their corresponding ddNTP, which may increase risk of virologic failures. The underlying pharmacological mechanisms may include but are not limited to, the competitive inhibition of anabolic enzymes, increase expression of efflux transporters and increase dATP and dGTP, where the resultant effect is reduced antiviral activity. Advisors/Committee Members: Burckart, Gilbert J. (Committee Chair), Louie, Stan (Committee Member), Shen, Wei-Chiang (Committee Member), D'Argenio, David (Committee Member), Wang, Clay C. C. (Committee Member).

Subjects/Keywords: nucleoside analog; NRTI; intracellular drug-drug interaction; efflux transporters; MRP2; MRP4; cellular adaptive response; ddNTP; TFV; ABC; ddI; endogenous nucleotide pools; PNP

Record Details Similar Records Cite « Share

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Bi, L. (2008). Intracellular drug-drug interaction between nucleoside analogs leads to early virologic failure in HIV patients receiving triple nucleoside combinations of tenofovir, lamivudine and abacavir or didanosine. (Doctoral Dissertation). University of Southern California. Retrieved from http://digitallibrary.usc.edu/cdm/compoundobject/collection/p15799coll127/id/47592/rec/3609

Chicago Manual of Style (16^th Edition):

Bi, Lucun. “Intracellular drug-drug interaction between nucleoside analogs leads to early virologic failure in HIV patients receiving triple nucleoside combinations of tenofovir, lamivudine and abacavir or didanosine.” 2008. Doctoral Dissertation, University of Southern California. Accessed January 22, 2021. http://digitallibrary.usc.edu/cdm/compoundobject/collection/p15799coll127/id/47592/rec/3609.

MLA Handbook (7^th Edition):

Bi, Lucun. “Intracellular drug-drug interaction between nucleoside analogs leads to early virologic failure in HIV patients receiving triple nucleoside combinations of tenofovir, lamivudine and abacavir or didanosine.” 2008. Web. 22 Jan 2021.

Vancouver:

Bi L. Intracellular drug-drug interaction between nucleoside analogs leads to early virologic failure in HIV patients receiving triple nucleoside combinations of tenofovir, lamivudine and abacavir or didanosine. [Internet] [Doctoral dissertation]. University of Southern California; 2008. [cited 2021 Jan 22]. Available from: http://digitallibrary.usc.edu/cdm/compoundobject/collection/p15799coll127/id/47592/rec/3609.

Council of Science Editors:

Bi L. Intracellular drug-drug interaction between nucleoside analogs leads to early virologic failure in HIV patients receiving triple nucleoside combinations of tenofovir, lamivudine and abacavir or didanosine. [Doctoral Dissertation]. University of Southern California; 2008. Available from: http://digitallibrary.usc.edu/cdm/compoundobject/collection/p15799coll127/id/47592/rec/3609

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