subject:(Stavudine)

Boston University

1. Brennan, Alana Teresa. Shifting to tenofovir use in first-line antiretroviral therapy for HIV-positive adults in public sector treatment programs in sub-Saharan Africa.

Degree: PhD, Epidemiology, 2016, Boston University

URL: http://hdl.handle.net/2144/19521

► The success of scale up of antiretroviral therapy (ART) in low- and middle-income countries (LMICs) is in large part due to the introduction of a… (more)

▼ The success of scale up of antiretroviral therapy (ART) in low- and middle-income countries (LMICs) is in large part due to the introduction of a “public health approach” to access advocated by the World Health Organization (WHO) which emphasized standardized treatment regimens that could be purchased in large quantities and delivered at scale. In 2010 the WHO updated their global HIV treatment guidelines recommending the substitution of stavudine with tenofovir (both of which are members of the non-nucleoside reverse transcriptase inhibitor (NRTI) class of drugs) in first-line antiretroviral therapy (ART). Given the size of treatment programs in sub-Saharan Africa, changing the NRTI used in first-line therapy for HIV could have a substantial impact on treatment outcomes. We conducted three prospective cohort studies using clinical datasets from several sub-Saharan African countries to answer questions surrounding the impacts of exposure to tenofovir in first-line therapy. The first study examines the frequency of stavudine use and single-drug substitutions (substituting the NRTI in first-line ART) in three regions in sub-Saharan Africa by calendar year, 2004–2014. We found a total of 33,441 (8.9%; 95% CI: 8.7–8.9%) single-drug substitutions occurred among 377,656 patients in the first 24 months on ART, close to 40% of which were amongst patients on stavudine. The decrease in single-drug substitutions corresponded with the phasing out of stavudine. We saw an 80% reduction in the risk of single-drug substitutions when comparing tenofovir to stavudine and close to a 70% reduction in the risk when comparing zidovudine to stavudine. The second study uses a regression discontinuity design to evaluate the impact of national HIV treatment guideline changes in South Africa and Zambia recommending tenofovir in first-line ART on treatment outcomes. We found that updated WHO guidelines increased the proportion of patients initiating tenofovir (risk difference (RD) (South Africa): 81%; 95% CI: 73%, 89%; RD (Zambia): 42%; 95% CI: 38%, 45%). Intent to treat estimates showed a decrease in single-drug substitutions in South Africa (RD: -15%; 95% CI: -18%, -12%) and Zambia (RD: -2.0%; 95% CI: -3.6%, -0.3%). In both countries, there was no effect on mortality, attrition or viral load failure (South Africa only). The third study investigates the effect of the 2012 tenofovir stock shortage in South Africa on provider and patient level outcomes, using data from four public-sector Right to Care clinics, two of which experienced a tenofovir stock shortage and two that did not. While imprecise, our results suggest a potential shift in how providers managed patients during the period of the shortage, mainly, a noticeable decrease in the average number of days between visits during the shortage compare to before or after at all four clinics and a significant difference in the proportion of patients missing visits. Difference-in-difference regression results showed a small, but significant, increase in the risk of missed visits during…

Subjects/Keywords: Epidemiology; HIV; Stavudine; Sub-Saharan Africa; Tenofovir; Zidovudine

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

APA (6^th Edition):

Brennan, A. T. (2016). Shifting to tenofovir use in first-line antiretroviral therapy for HIV-positive adults in public sector treatment programs in sub-Saharan Africa. (Doctoral Dissertation). Boston University. Retrieved from http://hdl.handle.net/2144/19521

Chicago Manual of Style (16^th Edition):

Brennan, Alana Teresa. “Shifting to tenofovir use in first-line antiretroviral therapy for HIV-positive adults in public sector treatment programs in sub-Saharan Africa.” 2016. Doctoral Dissertation, Boston University. Accessed March 06, 2021. http://hdl.handle.net/2144/19521.

MLA Handbook (7^th Edition):

Brennan, Alana Teresa. “Shifting to tenofovir use in first-line antiretroviral therapy for HIV-positive adults in public sector treatment programs in sub-Saharan Africa.” 2016. Web. 06 Mar 2021.

Vancouver:

Brennan AT. Shifting to tenofovir use in first-line antiretroviral therapy for HIV-positive adults in public sector treatment programs in sub-Saharan Africa. [Internet] [Doctoral dissertation]. Boston University; 2016. [cited 2021 Mar 06]. Available from: http://hdl.handle.net/2144/19521.

Council of Science Editors:

Brennan AT. Shifting to tenofovir use in first-line antiretroviral therapy for HIV-positive adults in public sector treatment programs in sub-Saharan Africa. [Doctoral Dissertation]. Boston University; 2016. Available from: http://hdl.handle.net/2144/19521

Stellenbosch University

2. Imran, Syed Ali. The reasons for changing HAART in HIV positive patients at the Thusong comprehensive care management and treatment site, West Rand district, Johannesburg, Gauteng.

Degree: MMed, Interdisciplinary Health Sciences, 2011, Stellenbosch University

URL: http://hdl.handle.net/10019.1/97249

► Objective To determine the reasons for the change or modification in the first line HAART regimen (1a and 1b) in HIV positive patients at the… (more)

Subjects/Keywords: HIV positive persons – Treatment; Highly active antiretroviral therapy (HAART); Stavudine – Side effects; UCTD; UCTD

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

APA (6^th Edition):

Imran, S. A. (2011). The reasons for changing HAART in HIV positive patients at the Thusong comprehensive care management and treatment site, West Rand district, Johannesburg, Gauteng. (Thesis). Stellenbosch University. Retrieved from http://hdl.handle.net/10019.1/97249

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):

Imran, Syed Ali. “The reasons for changing HAART in HIV positive patients at the Thusong comprehensive care management and treatment site, West Rand district, Johannesburg, Gauteng.” 2011. Thesis, Stellenbosch University. Accessed March 06, 2021. http://hdl.handle.net/10019.1/97249.

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

MLA Handbook (7^th Edition):

Imran, Syed Ali. “The reasons for changing HAART in HIV positive patients at the Thusong comprehensive care management and treatment site, West Rand district, Johannesburg, Gauteng.” 2011. Web. 06 Mar 2021.

Vancouver:

Imran SA. The reasons for changing HAART in HIV positive patients at the Thusong comprehensive care management and treatment site, West Rand district, Johannesburg, Gauteng. [Internet] [Thesis]. Stellenbosch University; 2011. [cited 2021 Mar 06]. Available from: http://hdl.handle.net/10019.1/97249.

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

Council of Science Editors:

Imran SA. The reasons for changing HAART in HIV positive patients at the Thusong comprehensive care management and treatment site, West Rand district, Johannesburg, Gauteng. [Thesis]. Stellenbosch University; 2011. Available from: http://hdl.handle.net/10019.1/97249

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

University of Georgia

3. Xu, Meng. Quantitative analysis and pharmacokinetics of antiviral agents in the pregnant rat.

Degree: 2014, University of Georgia

URL: http://hdl.handle.net/10724/25093

► Antiviral drugs are used therapeutically in pregnancy for treatment of both mother and fetus. Antiviral drugs are presumed to prevent viral transmission from mother to… (more)

Subjects/Keywords: Analytical; Pharmacokinetics; HIV; Zalcitabine; DDC; Stavudine; D4T; Lamivudine; 3TC; placental transport; fetal disposition

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

APA (6^th Edition):

Xu, M. (2014). Quantitative analysis and pharmacokinetics of antiviral agents in the pregnant rat. (Thesis). University of Georgia. Retrieved from http://hdl.handle.net/10724/25093

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):

Xu, Meng. “Quantitative analysis and pharmacokinetics of antiviral agents in the pregnant rat.” 2014. Thesis, University of Georgia. Accessed March 06, 2021. http://hdl.handle.net/10724/25093.

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

MLA Handbook (7^th Edition):

Xu, Meng. “Quantitative analysis and pharmacokinetics of antiviral agents in the pregnant rat.” 2014. Web. 06 Mar 2021.

Vancouver:

Xu M. Quantitative analysis and pharmacokinetics of antiviral agents in the pregnant rat. [Internet] [Thesis]. University of Georgia; 2014. [cited 2021 Mar 06]. Available from: http://hdl.handle.net/10724/25093.

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

Council of Science Editors:

Xu M. Quantitative analysis and pharmacokinetics of antiviral agents in the pregnant rat. [Thesis]. University of Georgia; 2014. Available from: http://hdl.handle.net/10724/25093

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

University of Pretoria

4. [No author]. Factors affecting response to antiretroviral agents at one year in an HIV cohort at Roma Hospital, Lesotho .

Degree: 2013, University of Pretoria

URL: http://upetd.up.ac.za/thesis/available/etd-05092013-133756/

► Objective: The objective of this retrospective cohort study is to assess whether demographic and anthropometric parameters, laboratory tests, co-morbidity, co-infection, treatment regimen, IRIS and adherence… (more)

▼ Objective: The objective of this retrospective cohort study is to assess whether demographic and anthropometric parameters, laboratory tests, co-morbidity, co-infection, treatment regimen, IRIS and adherence predict response to HAART as measured by CD4 count, weight gain and functional status in a cohort of patients in Roma, the Kingdom of Lesotho. Method: Data were collected from a computerised database of the Antiretroviral Centre of the hospital. A cohort of 300 subjects was identified from hospital records from January 2007. Each of these subjects was followed up over a period of 12 months with data obtained for at least two visits within the 12-month span. Data were obtained on weight and CD4 at baseline, three months and also at six and 12 months, and data for haemoglobin were obtained only at 12 months. Variables that may be potential confounders were identified and univariate and multivariate logistic regression analyses were carried out to establish differences independent of confounding factors for the combined endpoints, as well as for each endpoint separately. Results: Three-hundred patient records were analysed. Approximately 70% of the patients had a CD4 increase of at least 150 cells over baseline values at the end of the review period and in 52.3% of the patients an increase in weight of 10% over baseline measurements was seen. Seventy-nine patients (26.3%) had a haemoglobin level of at least 14g/dL at 12 months, regardless of baseline values or gender. The inclusion of Zidovudine (AZT) in treatment regimens was found in 73% of the patients and in multivariate analysis AZT was associated with not having anaemia at the end of the review period. However there was a slight reduction in haemoglobin level in the first two to three months of therapy in comparison with both Stavudine (d4T) and Tenofovir (TDF) but not significant enough to result in clinical anaemia. Baseline CD4 values were similar for all treatments options but dissimilar in other outcome variables and continued to vary significantly throughout the review period. The outcomes of multivariate analyses suggest that the male gender appears to have better response to HAART as seen in each of the multivariate models. The most important determinant of haemoglobin response was baseline haemoglobin values. In the haemoglobin-associated multivariate model, HAART is associated with an increase in haemoglobin over baseline values. A history of TB prior to HAART was a major factor in weight response and it is thought to be as a result of IRIS, which is the unmasking of latent infections as the immune system reconstitutes. CD4 values have no direct influence on weight however, but an increase in weight was observed in all therapy groups. Conclusion: Clinical and immunological parameters can be used to monitor response to HAART and predict treatment outcomes. These parameters can be organised into monitoring tools that will be useful in resource-limited areas. This study suggests that AZT-containing regimens appear not to result in anaemia and that… Advisors/Committee Members: Rheeder, Paul (advisor).

Subjects/Keywords: CD4; Weight; Haemoglobin; Resource-limited; Stavudine; Tenofovir anaemia; Zidovudine; Response; Highly active antiretroviral therapy (HAART); UCTD

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

APA (6^th Edition):

author], [. (2013). Factors affecting response to antiretroviral agents at one year in an HIV cohort at Roma Hospital, Lesotho . (Masters Thesis). University of Pretoria. Retrieved from http://upetd.up.ac.za/thesis/available/etd-05092013-133756/

Chicago Manual of Style (16^th Edition):

author], [No. “Factors affecting response to antiretroviral agents at one year in an HIV cohort at Roma Hospital, Lesotho .” 2013. Masters Thesis, University of Pretoria. Accessed March 06, 2021. http://upetd.up.ac.za/thesis/available/etd-05092013-133756/.

MLA Handbook (7^th Edition):

author], [No. “Factors affecting response to antiretroviral agents at one year in an HIV cohort at Roma Hospital, Lesotho .” 2013. Web. 06 Mar 2021.

Vancouver:

author] [. Factors affecting response to antiretroviral agents at one year in an HIV cohort at Roma Hospital, Lesotho . [Internet] [Masters thesis]. University of Pretoria; 2013. [cited 2021 Mar 06]. Available from: http://upetd.up.ac.za/thesis/available/etd-05092013-133756/.

Council of Science Editors:

author] [. Factors affecting response to antiretroviral agents at one year in an HIV cohort at Roma Hospital, Lesotho . [Masters Thesis]. University of Pretoria; 2013. Available from: http://upetd.up.ac.za/thesis/available/etd-05092013-133756/

5. Pereira, Thaisa Marinho. Avaliação da solubilidade e da permeabilidade intestinal de fármacos antirretrovirais. Aplicações na classificação biofarmacêutica.

Degree: Mestrado, Produção e Controle Farmacêuticos, 2012, University of São Paulo

URL: http://www.teses.usp.br/teses/disponiveis/9/9139/tde-12092012-113959/ ;

► A biodisponibilidade de um fármaco é o fator determinante da eficácia clínica e depende principalmente das seguintes etapas: liberação da substância ativa a partir da… (more)

▼ A biodisponibilidade de um fármaco é o fator determinante da eficácia clínica e depende principalmente das seguintes etapas: liberação da substância ativa a partir da forma farmacêutica e absorção. Assim, o controle da extensão e da velocidade de absorção de um fármaco administrado por via oral depende basicamente de dois aspectos: solubilidade nos líquidos fisiológicos e permeabilidade através das membranas biológicas. Fundamentado nestas características, o Sistema de Classificação Biofarmacêutica (SCB) foi proposto como ferramenta que permite a classificação dos fármacos e tem como finalidade auxiliar nas bioisenções e na predição da biodisponibilidade in vivo. Neste sentido, o presente trabalho teve como objetivo avaliar a solubilidade da estavudina e a permeabilidade intestinal de fármacos antirretrovirais por meio do modelo de perfusão in situ. Os meios empregados nos estudos de solubilidade e dissolução intrínseca foram: água purificada, tampão pH 1,2, tampão pH 4,5, tampão pH 6,8 e tampão pH 7,5. Para a determinação da solubilidade pelo método do equilíbrio (técnica shake-flask), quantidades conhecidas do fármaco foram adicionadas em cada meio até atingir a saturação e esta mistura foi submetida à agitação de 150 rpm por 72 horas a 37°C. Para os ensaios de dissolução intrínseca, quantidade conhecida de estavudina foi compactada na matriz do aparato de Wood e submetida à dissolução em cada meio, sob agitação de 50 rpm a 37°C. A determinação da permeabilidade dos antirretrovirais foi realizada empregando o modelo de perfusão in situ em ratos machos Wistar. Uma porção do jejuno foi isolada e a solução de perfusão (pH 6,5) contendo o fármaco foi perfundida a um fluxo de 0,2 mL.min-1 a 37°C por 120 minutos. Os resultados obtidos referentes à solubilidade da estavudina pelo método do equilíbrio foram (em mg.mL-1): 146,49 (água), 149,22 (pH 4,5), 139,43 (pH 6,8) e 130,15 (pH 7,5). A determinação da razão dose:solubilidade (D:S) em cada meio permitiu a obtenção dos seguintes resultados (em mL): 0,27 (água), 0,27 (pH 4,5), 0,29 (pH 6,8) e 0,31 (pH 7,5). Tais dados indicaram que este fármaco apresenta alta solubilidade nos meios utilizados no estudo, exceto em meio pH 1,2, onde a estavudina apresentou instabilidade demonstrada pela presença de coloração e odor alterados, inviabilizando a determinação da solubilidade nestas condições. Os ensaios de dissolução intrínseca da estavudina permitiram a determinação das taxas de dissolução intrínseca (TDI), as quais foram (em mg/min/cm²): 2,3570 (água), 2,7389 (pH 1,2), 2,7590 (pH 4,5) e 2,5947 (pH 6,8), demonstrando que este fármaco apresenta alta velocidade de dissolução nos meios utilizados. Com relação ao estudo de permeabilidade por meio do modelo de perfusão in situ, nas condições experimentais empregadas, os resultados obtidos foram (em cm.s-1): 3,96 x 10-5 (estavudina), 3,08 x 10-5 (lamivudina) e 4,17 x 10-5 (zidovudina) sugerindo que os fármacos estavudina e zidovudina apresentam alta permeabilidade. Para a lamivudina não é descartada a possibilidade de ser considerada… Advisors/Committee Members: Serra, Cristina Helena dos Reis.

Subjects/Keywords: Antiretrovirals; Antirretrovirais; Biofarmácia; Biopharmacy; Estavudina; in situ Perfusion; Lamivudina; Lamivudine; Perfusão in situ; Permeabilidade; Permeability; Solubilidade; Solubility; Stavudine; Zidovudina; Zidovudine

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

APA (6^th Edition):

Pereira, T. M. (2012). Avaliação da solubilidade e da permeabilidade intestinal de fármacos antirretrovirais. Aplicações na classificação biofarmacêutica. (Masters Thesis). University of São Paulo. Retrieved from http://www.teses.usp.br/teses/disponiveis/9/9139/tde-12092012-113959/ ;

Chicago Manual of Style (16^th Edition):

Pereira, Thaisa Marinho. “Avaliação da solubilidade e da permeabilidade intestinal de fármacos antirretrovirais. Aplicações na classificação biofarmacêutica.” 2012. Masters Thesis, University of São Paulo. Accessed March 06, 2021. http://www.teses.usp.br/teses/disponiveis/9/9139/tde-12092012-113959/ ;.

MLA Handbook (7^th Edition):

Pereira, Thaisa Marinho. “Avaliação da solubilidade e da permeabilidade intestinal de fármacos antirretrovirais. Aplicações na classificação biofarmacêutica.” 2012. Web. 06 Mar 2021.

Vancouver:

Pereira TM. Avaliação da solubilidade e da permeabilidade intestinal de fármacos antirretrovirais. Aplicações na classificação biofarmacêutica. [Internet] [Masters thesis]. University of São Paulo; 2012. [cited 2021 Mar 06]. Available from: http://www.teses.usp.br/teses/disponiveis/9/9139/tde-12092012-113959/ ;.

Council of Science Editors:

Pereira TM. Avaliação da solubilidade e da permeabilidade intestinal de fármacos antirretrovirais. Aplicações na classificação biofarmacêutica. [Masters Thesis]. University of São Paulo; 2012. Available from: http://www.teses.usp.br/teses/disponiveis/9/9139/tde-12092012-113959/ ;

University of Pretoria

6. Adebanjo, Adefolarin Babafemi. Factors affecting response to antiretroviral agents at one year in an HIV cohort at Roma Hospital, Lesotho.

Degree: Clinical Epidemiology, 2012, University of Pretoria

URL: http://hdl.handle.net/2263/24507

► Objective: The objective of this retrospective cohort study is to assess whether demographic and anthropometric parameters, laboratory tests, co-morbidity, co-infection, treatment regimen, IRIS and adherence… (more)

▼ Objective: The objective of this retrospective cohort study is to assess whether demographic and anthropometric parameters, laboratory tests, co-morbidity, co-infection, treatment regimen, IRIS and adherence predict response to HAART as measured by CD4 count, weight gain and functional status in a cohort of patients in Roma, the Kingdom of Lesotho. Method: Data were collected from a computerised database of the Antiretroviral Centre of the hospital. A cohort of 300 subjects was identified from hospital records from January 2007. Each of these subjects was followed up over a period of 12 months with data obtained for at least two visits within the 12-month span. Data were obtained on weight and CD4 at baseline, three months and also at six and 12 months, and data for haemoglobin were obtained only at 12 months. Variables that may be potential confounders were identified and univariate and multivariate logistic regression analyses were carried out to establish differences independent of confounding factors for the combined endpoints, as well as for each endpoint separately. Results: Three-hundred patient records were analysed. Approximately 70% of the patients had a CD4 increase of at least 150 cells over baseline values at the end of the review period and in 52.3% of the patients an increase in weight of 10% over baseline measurements was seen. Seventy-nine patients (26.3%) had a haemoglobin level of at least 14g/dL at 12 months, regardless of baseline values or gender. The inclusion of Zidovudine (AZT) in treatment regimens was found in 73% of the patients and in multivariate analysis AZT was associated with not having anaemia at the end of the review period. However there was a slight reduction in haemoglobin level in the first two to three months of therapy in comparison with both Stavudine (d4T) and Tenofovir (TDF) but not significant enough to result in clinical anaemia. Baseline CD4 values were similar for all treatments options but dissimilar in other outcome variables and continued to vary significantly throughout the review period. The outcomes of multivariate analyses suggest that the male gender appears to have better response to HAART as seen in each of the multivariate models. The most important determinant of haemoglobin response was baseline haemoglobin values. In the haemoglobin-associated multivariate model, HAART is associated with an increase in haemoglobin over baseline values. A history of TB prior to HAART was a major factor in weight response and it is thought to be as a result of IRIS, which is the unmasking of latent infections as the immune system reconstitutes. CD4 values have no direct influence on weight however, but an increase in weight was observed in all therapy groups. Conclusion: Clinical and immunological parameters can be used to monitor response to HAART and predict treatment outcomes. These parameters can be organised into monitoring tools that will be useful in resource-limited areas. This study suggests that AZT-containing regimens appear not to result in anaemia and that… Advisors/Committee Members: Rheeder, Paul (advisor).

Subjects/Keywords: CD4; Weight; Haemoglobin; Resource-limited; Stavudine; Tenofovir anaemia; Zidovudine; Response; Highly active antiretroviral therapy (HAART); UCTD

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

APA (6^th Edition):

Adebanjo, A. (2012). Factors affecting response to antiretroviral agents at one year in an HIV cohort at Roma Hospital, Lesotho. (Masters Thesis). University of Pretoria. Retrieved from http://hdl.handle.net/2263/24507

Chicago Manual of Style (16^th Edition):

Adebanjo, Adefolarin. “Factors affecting response to antiretroviral agents at one year in an HIV cohort at Roma Hospital, Lesotho.” 2012. Masters Thesis, University of Pretoria. Accessed March 06, 2021. http://hdl.handle.net/2263/24507.

MLA Handbook (7^th Edition):

Adebanjo, Adefolarin. “Factors affecting response to antiretroviral agents at one year in an HIV cohort at Roma Hospital, Lesotho.” 2012. Web. 06 Mar 2021.

Vancouver:

Adebanjo A. Factors affecting response to antiretroviral agents at one year in an HIV cohort at Roma Hospital, Lesotho. [Internet] [Masters thesis]. University of Pretoria; 2012. [cited 2021 Mar 06]. Available from: http://hdl.handle.net/2263/24507.

Council of Science Editors:

Adebanjo A. Factors affecting response to antiretroviral agents at one year in an HIV cohort at Roma Hospital, Lesotho. [Masters Thesis]. University of Pretoria; 2012. Available from: http://hdl.handle.net/2263/24507

University of Georgia

7. 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 March 06, 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. 06 Mar 2021.

Vancouver:

Blue SK. Pharmacokinetics of anti-HIV agents in rodents. [Internet] [Thesis]. University of Georgia; 2014. [cited 2021 Mar 06]. 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

Stellenbosch University

8. Innes, Steven Eugene Vere. Lipoatrophy in HIV-infected children on antiretroviral therapy.

Degree: PhD, Paediatrics and Child Health, 2013, Stellenbosch University

URL: http://hdl.handle.net/10019.1/79864

►

Bibliography

ENGLISH ABSTRACT: Introduction: Lipoatrophy is a common adverse effect of stavudine and this effect is strongly dose-dependent. Stavudine remains the most commonly used paediatric… (more)

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Bibliography

ENGLISH ABSTRACT: Introduction: Lipoatrophy is a common adverse effect of stavudine and this effect is strongly dose-dependent. Stavudine remains the most commonly used paediatric antiretroviral drug in sub-Saharan Africa, yet when the current study began in 2009, the prevalence and severity of lipoatrophy in children on antiretroviral therapy in sub-Saharan Africa had never been studied. The development of lipoatrophy may have serious and far-reaching consequences for patients and their families. The off-label stavudine dosing method, prescribed to children whose caregivers do not have access to a refrigerator, in which the contents of an adult capsule is mixed into tap water, has potential for over-dosing or under-dosing. In addition, children on stavudine continue to be exposed to a disproportionately high dose out of line with the reduced adult dose. Aims: 1. a) To investigate the prevalence and risk factors for lipoatrophy in HIV-infected children in Southern Africa b) To identify a simple anthropometric screening tool to detect early lipoatrophy in children 2. To validate the off-label stavudine dosing method prescribed to children whose caregivers do not have access to a refrigerator, with a view to reducing the recommended dose and thereby the side-effects. Methods: 1. a) We recruited pre-pubertal children on antiretroviral therapy from a family HIV clinic in our facility. Lipoatrophy was identified by two experienced paediatric HIV clinicians using a standardized grading scale. A dietician performed dietary assessment and anthropometric measurements. Previous antiretroviral exposures were recorded. A subset of recruits received Dual-Energy X-ray Absorbtiometry scanning. b) Anthropometric measurements in children with and without lipoatrophy were compared using multivariate linear regression adjusting for age and gender. The most discerning anthropometric variables underwent Receiver Operating Characteristic curve analysis to identify the most appropriate diagnostic cut-off. 2. a) Accuracy of the standard off-label stavudine dosing method was investigated using high-performance liquid chromatography to recover active drug from solutions made up using the prescribed method. This was compared to the stated drug content of the capsules. b) Bioavailability was investigated by performing a randomized crossover pharmacokinetic study wherein healthy HIV-seronegative adult volunteers received one of two generic stavudine capsule formulations, either intact or mixed in water using the prescribed method. Plasma stavudine concentrations were assayed by liquid chromatography tandem mass spectrometry. Results: 1. a) Prevalence of lipoatrophy was 36%, and incidence was 12% per person-year. Adjusted odds ratio for developing lipoatrophy was 1.9 (CI: 1.3–2.9) for each additional year of accumulated exposure to standard-dose stavudine. b) Baseline biceps skin-fold thickness correlated well with maximum lipoatrophy grading score at any site, giving a partial correlation coefficient of 0.33…

Advisors/Committee Members: Cotton, Mark Fredric, Rosenkranz, Bernd, Rabie, Helena, Zollner, Ekkehard Werner, Stellenbosch University. Faculty of Medicine and Health Sciences. Dept. of Paediatrics and Child Health..

Subjects/Keywords: Pediatrics; Dissertations – Pediatrics; Lipoatrophy – HIV-positive children – Risk factors; HIV positive children – Treatment; Antiretroviral agents – Risk factors; Stavudine – Therapeutic use; Pediatrics and Child Health

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

APA (6^th Edition):

Innes, S. E. V. (2013). Lipoatrophy in HIV-infected children on antiretroviral therapy. (Doctoral Dissertation). Stellenbosch University. Retrieved from http://hdl.handle.net/10019.1/79864

Chicago Manual of Style (16^th Edition):

Innes, Steven Eugene Vere. “Lipoatrophy in HIV-infected children on antiretroviral therapy.” 2013. Doctoral Dissertation, Stellenbosch University. Accessed March 06, 2021. http://hdl.handle.net/10019.1/79864.

MLA Handbook (7^th Edition):

Innes, Steven Eugene Vere. “Lipoatrophy in HIV-infected children on antiretroviral therapy.” 2013. Web. 06 Mar 2021.

Vancouver:

Innes SEV. Lipoatrophy in HIV-infected children on antiretroviral therapy. [Internet] [Doctoral dissertation]. Stellenbosch University; 2013. [cited 2021 Mar 06]. Available from: http://hdl.handle.net/10019.1/79864.

Council of Science Editors:

Innes SEV. Lipoatrophy in HIV-infected children on antiretroviral therapy. [Doctoral Dissertation]. Stellenbosch University; 2013. Available from: http://hdl.handle.net/10019.1/79864

9. Taborianski, Andréia Montoro. Validação de métodos para análise e estudos de estabilidade de anti-retrovirais em preparações farmacêuticas.

Degree: Mestrado, Produção e Controle Farmacêuticos, 2003, University of São Paulo

URL: http://www.teses.usp.br/teses/disponiveis/9/9139/tde-15102003-165120/ ;

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A síndrome da imunodeficiência adquirida é causada pelo vírus da imunodeficiência humana e é caracterizada por provocar depleção física e funcional do sistema imune do… (more)

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A síndrome da imunodeficiência adquirida é causada pelo vírus da imunodeficiência humana e é caracterizada por provocar depleção física e funcional do sistema imune do organismo, através da infecção citopática de células CD4+. Muitos fármacos anti-retrovirais tem sido desenvolvidos e estão disponíveis comercialmente. Para atuar no controle de qualidade de medicamentos deve-se continuamente estudar o desenvolvimento e a validação de novas metodologias para quantificação de fármacos, para serem aplicadas nos estudos de estabilidade de formulações farmacêuticas e na análise de produtos de degradação. Neste trabalho foram utilizadas duas técnicas analíticas, a espectrofotometria direta no UV/VIS e a cromatografia líquida de alta eficiência (CLAE), para a determinação quantitativa de zidovudina (AZT) e estavudina (d4T).em medicamentos. Ambos os métodos foram validados com relação à linearidade, exatidão, precisão, especificidade e limite de detecção e quantificação. O método validado para a CLAE foi também empregado para a determinação quantitativa da timina, produto de degradação do AZT e da d4T. A metodologia validada por CLAE foi utilizada na realização de estudos de estabilidade acelerada dos anti-retrovirais contidos nas diferentes preparações farmacêuticas. Realizou-se o estudo da estabilidade em três diferentes condições: temperatura ambiente, 40 °C / 75% UR e 50 °C / 90% UR. Tanto a zidovudina (Fabricante A) e estavudina (Fabricante B) apresentaram decaimento cinético de zero ordem com prazos de validade a 50 °C / 90% UR de 10, 3 e 2 meses, respectivamente.

The acquired immunodeficiency syndrome is characterized by causing physical and functional depletion of the organisms immune system, through the cytophatic infection of CD4+ cells. Several antiretroviral drugs has been developed and commercially made available. In order to assure the quality control of drugs it is necessary to develop and validate new analytical methodologies to perform the quantitative determination of drugs and stability studies of pharmaceutical formulations by determining the drug itself and its degradation products. In this research two analytical techniques, direct UV/VIS spectrophotometry and high performance liquid chromatography (HPLC), were used for the quantitative determination of zidovudine (AZT) and stavudine (d4T) in pharmaceutical preparations. Both methods were validated and parameters like linearity, precision, accuracy, specificity, limit of detection and limit of quantification, were determined. The validated HPLC method was also applied for quantitative determination of timine, a degradation product of AZT and d4T. The validated HPLC method was applied to accelerate stability studies of AZT and d4T in different pharmaceutical preparations. The stability studies were performed at three different conditions: room temperature, 40 °C / 75% RH and 50 °C / 90% RH. Both AZT and d4T (Industry A) and d4T (Industry B) pharmaceutical preparations presented a zero order degradation reaction. The three formulations presented a…

Advisors/Committee Members: Santoro, Maria Ines Rocha Miritello.

Subjects/Keywords: accelerated stability studies; estavudina; estudos de estabilidade acelerada; stavudine; validação de métodos analíticos; validation of analytical methods; zidovudina; zidovudine

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

APA (6^th Edition):

Taborianski, A. M. (2003). Validação de métodos para análise e estudos de estabilidade de anti-retrovirais em preparações farmacêuticas. (Masters Thesis). University of São Paulo. Retrieved from http://www.teses.usp.br/teses/disponiveis/9/9139/tde-15102003-165120/ ;

Chicago Manual of Style (16^th Edition):

Taborianski, Andréia Montoro. “Validação de métodos para análise e estudos de estabilidade de anti-retrovirais em preparações farmacêuticas.” 2003. Masters Thesis, University of São Paulo. Accessed March 06, 2021. http://www.teses.usp.br/teses/disponiveis/9/9139/tde-15102003-165120/ ;.

MLA Handbook (7^th Edition):

Taborianski, Andréia Montoro. “Validação de métodos para análise e estudos de estabilidade de anti-retrovirais em preparações farmacêuticas.” 2003. Web. 06 Mar 2021.

Vancouver:

Taborianski AM. Validação de métodos para análise e estudos de estabilidade de anti-retrovirais em preparações farmacêuticas. [Internet] [Masters thesis]. University of São Paulo; 2003. [cited 2021 Mar 06]. Available from: http://www.teses.usp.br/teses/disponiveis/9/9139/tde-15102003-165120/ ;.

Council of Science Editors:

Taborianski AM. Validação de métodos para análise e estudos de estabilidade de anti-retrovirais em preparações farmacêuticas. [Masters Thesis]. University of São Paulo; 2003. Available from: http://www.teses.usp.br/teses/disponiveis/9/9139/tde-15102003-165120/ ;

North-West University

10. Botha, Mario Matthew. Pre-clinical evaluation of the possible enhancement of the efficacy of antiretroviral drugs by pheroid technology / M.M. Botha .

Degree: 2007, North-West University

URL: http://hdl.handle.net/10394/1064

► HIV/AIDS is the most threatening and challenging infectious diseases of our time, with the highest increase of newly infected cases reported. This infectious disease was… (more)

▼ HIV/AIDS is the most threatening and challenging infectious diseases of our time, with the highest increase of newly infected cases reported. This infectious disease was discovered in the early eighties under homosexual men and was later to be discovered in heterosexuals. HIV is a systemic immunosuppressive disorder which causes a depletion of CD4+ T cells and develops into the acquired immunodeficiency syndrome - AIDS. Africa is the continent most affected by HIV/AIDS with the southern parts of Africa having the highest prevalence rates compared to the rest of Africa. Statistics indicate that AIDS is responsible for 3% of deaths in children worldwide - one in seven people dying of an HIV-related illness is a child under the age of 15 years. It was stated by the WHO that countries should develop improved antiretrovirals regimes for the prevention of mother-to-child transmission. Difficulties in administering antiretrovirals (ARVs) to patients (especially children) are the strict dosage regimes and the severe adverse reactions. These factors complicate patient adherence. The list of problems in treating patients is endless and includes the distribution, stability as well as the low efficacy of these drugs. Most of the above mentioned problems and obstacles related to ARVs and ARV treatment could be minimized or eliminated by the use of a stable and effective drug delivery system. Enhancing ARV treatment may be accomplished by the use of the Pheroid™ drug delivery system. Pheroids™ consists mainly of fatty acids and sterile nitrous oxide gassed water. Pharmacological active substances are entrapped into submicron and micron sized structures called Pheroids™. Research showed promising results and advantages in delivering drugs through oral and transdermal routes using Pheroid™ technology. The focus of this study was to test the possible enhancement of the efficacy of antiretrovirals using Pheroid™ technology. The assays used to study this possible enhancement were a modified neutral red and a modified 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium (MTT) assay. These assays confirmed and illustrated the toxic and protective properties of the tested ARVs (stavudine, lamivudine and nevirapine). An MT-2 cell line was used and infected with an HIV-1 strain, SW7-TCL. Applying Pheroid™ technology in these assays resulted in massive cell death, due to increased ARV toxic levels within the cells. Viability tests proved that Pheroids™ had no effect on the viability of cells at the concentration typically used. This confirmed the enhancing properties of Pheroids™ in the delivery of drugs into the cells. The MTT assay was further adapted from a seven day incubation period to a three day incubation period. By using a low concentration series and a three day incubation period the loss of cells through toxicity was partially overcome. One of the problems that arose form this study was the non-reproducibility of the results. Absorbance levels fluctuated at specific concentrations of the same ARV, which cause…

Subjects/Keywords: Lamivudine (3TC); Stavudine (d4T); MTT; Finter's neutral red; Pheroid; Antiretroviral (ARV); HIV and AIDS; Viability

Record Details Similar Records Cite « Share

❌

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

APA (6^th Edition):

Botha, M. M. (2007). Pre-clinical evaluation of the possible enhancement of the efficacy of antiretroviral drugs by pheroid technology / M.M. Botha . (Thesis). North-West University. Retrieved from http://hdl.handle.net/10394/1064

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):

Botha, Mario Matthew. “Pre-clinical evaluation of the possible enhancement of the efficacy of antiretroviral drugs by pheroid technology / M.M. Botha .” 2007. Thesis, North-West University. Accessed March 06, 2021. http://hdl.handle.net/10394/1064.

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

MLA Handbook (7^th Edition):

Botha, Mario Matthew. “Pre-clinical evaluation of the possible enhancement of the efficacy of antiretroviral drugs by pheroid technology / M.M. Botha .” 2007. Web. 06 Mar 2021.

Vancouver:

Botha MM. Pre-clinical evaluation of the possible enhancement of the efficacy of antiretroviral drugs by pheroid technology / M.M. Botha . [Internet] [Thesis]. North-West University; 2007. [cited 2021 Mar 06]. Available from: http://hdl.handle.net/10394/1064.

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

Council of Science Editors:

Botha MM. Pre-clinical evaluation of the possible enhancement of the efficacy of antiretroviral drugs by pheroid technology / M.M. Botha . [Thesis]. North-West University; 2007. Available from: http://hdl.handle.net/10394/1064

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

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Open Access Theses and Dissertations