The Experts below are selected from a list of 1434 Experts worldwide ranked by ideXlab platform
Quarraisha Abdool Karim - One of the best experts on this subject based on the ideXlab platform.
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Ex vivo HIV entry into blood CD4+ T cells does not predict heterosexual HIV acquisition in women
PloS one, 2018Co-Authors: Vineet Joag, Quarraisha Abdool Karim, Salim S. Abdool Karim, Nonhlanhla Yende-zuma, Natasha Samsunder, Lyle R. Mckinnon, Aida Sivro, Hajra. Imam, Rupert KaulAbstract:Background: A blood-based assay that could quantify HIV susceptibility would be very valuable for HIV prevention research. Previously, we developed and validated an ex vivo, flow-based, HIV entry assay to assess genital HIV susceptibility in endocervical CD4+ T cells. Methods: Here we assessed whether this tool could be used to predict HIV risk using blood-derived CD4+ T cells in a rigorously-blinded, nested case-control study using blood samples collected from high-risk, HIV-uninfected South African women enrolled in the CAPRISA 004 clinical trial. Cases, subsequently acquiring HIV were sampled prior to HIV infection and compared with controls, who remained HIV-uninfected. The primary endpoint was ex vivo entry of a CCR5-tropic HIV founder virus into blood CD4+ T cells. Secondary endpoints included HIV entry into CD4+ central (TCM) and effector (TEM) memory T cells, and into CD4+ T cell subsets expressing CCR5, CD69, CCR6, α4β1 or α4β7. Results: Compared to bulk CD4+ T cells (4.9% virus entry), CD4+ T cells expressing CCR5, CCR6 or α4β1 and TEM were highly susceptible (15.5%, 8.8%, 8.2% and 10.8% entry, respectively, all p
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Antiretrovirals for HIV Prevention: The CAPRISA 004 Tenofovir Gel Trial
The CAPRISA Clinical Trials: HIV Treatment and Prevention, 2017Co-Authors: Cheryl Baxter, Leila E Mansoor, Salim S. Abdool Karim, Tanuja N. Gengiah, Quarraisha Abdool KarimAbstract:Women bear a disproportionate burden of the HIV epidemic in sub-Saharan Africa. Young women, including adolescent girls, unable to negotiate mutual faithfulness and/or condom use with their male partners are particularly vulnerable and have few HIV prevention options available to them that they can directly control. The development of technologies such as microbicides to prevent sexual acquisition of HIV infection in young women was therefore an urgent priority. Unfortunately, all of the microbicide trials assessing first and second generation products produced disappointing results. In 2007, CAPRISA initiated a phase IIb, two-arm, double-blind, randomised, controlled trial to evaluate the effectiveness and safety of the first antiretroviral-based microbicide, tenofovir gel, for the prevention of sexually transmitted HIV infection. This chapter focuses on CAPRISA’s experiences in developing the protocol with specific reference to how the lessons from past microbicide trials helped shape the development of the trial. The scientific rationale behind the dosing strategy selected for the study is provided and some of the challenges encountered during the study that may have wider implications for other research trials are described. The chapter is concluded with a brief summary of the trial results and their implications for the HIV prevention field.
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S17.2 Hpv infection, genital inflammation, and hiv risk in the CAPRISA 004 trial
Sexually Transmitted Infections, 2015Co-Authors: Quarraisha Abdool Karim, Jo Ann S. Passmore, Ayesha B. M. Kharsany, Anneke Grobler, Natasha Samsunder, Lenine J. Liebenberg, Kerry. Leask, Lyle R. Mckinnon, Salim S. Abdool KarimAbstract:There is a growing body of data demonstrating an increased risk for HIV acquisition in the presence of HPV infection, but the mechanism of this relationship is unclear. This study investigated the impact of HPV infection on both genital inflammation and HIV risk in the CAPRISA 004 1% TFV gel trial. Baseline cervicovaginal lavage specimens collected from 737 HIV-uninfected women were analysed to determine the prevalence of HPV infection. Clinical, reproductive, demographic and behavioral data were captured. The presence of DNA from 37 HPV genotypes was assessed using Linear Array, and the concentrations of 48 relevant cytokines were quantified by multiplexed ELISA assays. The presence of HIV was measured monthly using two rapid tests and confirmed by western blot and PCR. Of the 737 eligible participants, 74% had prevalent HPV-infection (95% CI: 71–77%). Participants with prevalent HPV infection were 2.8 times more likely to acquire HIV infection compared to those with no HPV infection (95% CI: 1.3–5.9; p = 0.007). HIV risk was independent of the oncogenicity of HPV strains at baseline [(HPV oncogenic strains HR 2.5 (95% CI 1.0–6.2) vs non-oncogenic strains HR 2.1 (95% CI 0.9–5.1)], and was also increased in the presence of multiple concurrent infections (HR 3.1; 95% CI 1.4–6.8). No cytokine signatures were associated with prevalent HPV infection. The use of tenofovir gel did not prevent HPV infection. These data confirm a relationship between HPV infection and increased risk for HIV acquisition, and underscores the need to define the underlying biological mechanisms to inform targeted interventions in settings that bear a high burden of both infections.
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tenofovir gel for the prevention of herpes simplex virus type 2 infection
The New England Journal of Medicine, 2015Co-Authors: Quarraisha Abdool Karim, Cheryl Baxter, Ayesha B. M. Kharsany, Anna Christina. Grobler, Salim Abdool S Karim, Lise. WernerAbstract:BACKGROUND Globally, herpes simplex virus type 2 (HSV-2) infection is the most common cause of genital ulcer disease. Effective prevention strategies for HSV-2 infection are needed to achieve the goals of the World Health Organization global strategy for the prevention and control of sexually transmitted infections. METHODS We assessed the effectiveness of pericoital tenofovir gel, an antiviral microbicide, in preventing HSV-2 acquisition in a subgroup of 422 HSV-2–negative women enrolled in the Centre for the AIDS Programme of Research in South Africa (CAPRISA) 004 study, a double-blind, randomized, placebo-controlled trial. Incident HSV-2 cases were identified by evidence of seroconversion on an HSV-2 IgG enzyme-linked immunosorbent assay between study enrollment and exit. A confirmatory analysis was performed by Western blot testing. RESULTS The HSV-2 incidence rate was 10.2 cases per 100 person-years (95% confidence interval [CI], 6.8 to 14.7) among 202 women assigned to tenofovir gel, as compared with 21.0 cases per 100 person-years (95% CI, 16.0 to 27.2) among 222 women assigned to placebo gel (incidence rate ratio, 0.49; 95% CI, 0.30 to 0.77; P = 0.003). The HSV-2 incidence rate among the 25 women with vaginal tenofovir concentrations of 10,000 ng per milliliter or more was 5.7 cases per 100 person-years, as compared with 15.5 cases per 100 person-years among the 103 women with no detectable vaginal tenofovir (incidence rate ratio, 0.37; 95% CI, 0.04 to 1.51; P = 0.14). As confirmed by Western blot testing, there were 16 HSV-2 seroconversions among women assigned to tenofovir gel as compared with 36 among those assigned to the placebo gel (incidence rate ratio, 0.45; 95% CI, 0.23 to 0.82; P = 0.005). CONCLUSIONS In this study in South Africa, pericoital application of tenofovir gel reduced HSV-2 acquisition in women. (Funded by the U.S. Agency for International Development and others; ClinicalTrials.gov number, NCT00441298.)
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Genital tenofovir concentrations correlate with protection against HIV infection in the CAPRISA 004 trial: Importance of adherence for microbicide effectiveness
Journal of acquired immune deficiency syndromes (1999), 2015Co-Authors: Tanuja N. Gengiah, Quarraisha Abdool Karim, Lise. Werner, Kuo-hsiung. Yang, Nicole White, Salim S. Abdool KarimAbstract:OBJECTIVE: The CAPRISA 004 trial showed that coitally dosed tenofovir 1% gel reduced HIV acquisition by 39% overall and 54% when used consistently. The objective of this analysis was to ascertain its pharmacokinetic-pharmacodynamic relationship to protect against HIV acquisition. DESIGN: Genital and systemic tenofovir concentrations in 34 women who acquired HIV (cases) were compared with 302 randomly selected women who remained HIV uninfected (controls) during the CAPRISA 004 trial. In total 336 cervicovaginal fluid (CVF) 55 plasma and 23 paired cervical and vaginal tissue samples were assayed by validated methods for tenofovir and tenofovir diphosphate (tenofovir-DP) detection. RESULTS: Tenofovir was detected in the genital tract in 8 (23.5%) cases and 119 (39.4%) controls (P = 0.076). Among those with detectable genital tract tenofovir the median CVF concentrations were 97% lower in cases compared with controls 476 versus 13821 ng/mL (P = 0.107). A total of 14.7% (5/34) of cases and 32.8% (99/302) of controls were found to have tenofovir CVF concentrations above 100 ng/mL [odds ratio (OR): 0.35 P = 0.037]. At a higher threshold 8.8% (3/34) of cases and 26.2% (79/302) of controls were found to have tenofovir CVF concentrations above 1000 ng/mL (OR: 0.27 P = 0.036). Plasma tenofovir concentrations were /=100 ng/mL in CVF was associated with 65% (95% CI: 6% to 87%) protection against HIV whereas a >/=1000 ng/mL concentration correlated with 76% (95% CI: 8% to 92%) protection against HIV infection.
Salim S. Abdool Karim - One of the best experts on this subject based on the ideXlab platform.
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Ex vivo HIV entry into blood CD4+ T cells does not predict heterosexual HIV acquisition in women
PloS one, 2018Co-Authors: Vineet Joag, Quarraisha Abdool Karim, Salim S. Abdool Karim, Nonhlanhla Yende-zuma, Natasha Samsunder, Lyle R. Mckinnon, Aida Sivro, Hajra. Imam, Rupert KaulAbstract:Background: A blood-based assay that could quantify HIV susceptibility would be very valuable for HIV prevention research. Previously, we developed and validated an ex vivo, flow-based, HIV entry assay to assess genital HIV susceptibility in endocervical CD4+ T cells. Methods: Here we assessed whether this tool could be used to predict HIV risk using blood-derived CD4+ T cells in a rigorously-blinded, nested case-control study using blood samples collected from high-risk, HIV-uninfected South African women enrolled in the CAPRISA 004 clinical trial. Cases, subsequently acquiring HIV were sampled prior to HIV infection and compared with controls, who remained HIV-uninfected. The primary endpoint was ex vivo entry of a CCR5-tropic HIV founder virus into blood CD4+ T cells. Secondary endpoints included HIV entry into CD4+ central (TCM) and effector (TEM) memory T cells, and into CD4+ T cell subsets expressing CCR5, CD69, CCR6, α4β1 or α4β7. Results: Compared to bulk CD4+ T cells (4.9% virus entry), CD4+ T cells expressing CCR5, CCR6 or α4β1 and TEM were highly susceptible (15.5%, 8.8%, 8.2% and 10.8% entry, respectively, all p
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Antiretrovirals for HIV Prevention: The CAPRISA 004 Tenofovir Gel Trial
The CAPRISA Clinical Trials: HIV Treatment and Prevention, 2017Co-Authors: Cheryl Baxter, Leila E Mansoor, Salim S. Abdool Karim, Tanuja N. Gengiah, Quarraisha Abdool KarimAbstract:Women bear a disproportionate burden of the HIV epidemic in sub-Saharan Africa. Young women, including adolescent girls, unable to negotiate mutual faithfulness and/or condom use with their male partners are particularly vulnerable and have few HIV prevention options available to them that they can directly control. The development of technologies such as microbicides to prevent sexual acquisition of HIV infection in young women was therefore an urgent priority. Unfortunately, all of the microbicide trials assessing first and second generation products produced disappointing results. In 2007, CAPRISA initiated a phase IIb, two-arm, double-blind, randomised, controlled trial to evaluate the effectiveness and safety of the first antiretroviral-based microbicide, tenofovir gel, for the prevention of sexually transmitted HIV infection. This chapter focuses on CAPRISA’s experiences in developing the protocol with specific reference to how the lessons from past microbicide trials helped shape the development of the trial. The scientific rationale behind the dosing strategy selected for the study is provided and some of the challenges encountered during the study that may have wider implications for other research trials are described. The chapter is concluded with a brief summary of the trial results and their implications for the HIV prevention field.
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S17.2 Hpv infection, genital inflammation, and hiv risk in the CAPRISA 004 trial
Sexually Transmitted Infections, 2015Co-Authors: Quarraisha Abdool Karim, Jo Ann S. Passmore, Ayesha B. M. Kharsany, Anneke Grobler, Natasha Samsunder, Lenine J. Liebenberg, Kerry. Leask, Lyle R. Mckinnon, Salim S. Abdool KarimAbstract:There is a growing body of data demonstrating an increased risk for HIV acquisition in the presence of HPV infection, but the mechanism of this relationship is unclear. This study investigated the impact of HPV infection on both genital inflammation and HIV risk in the CAPRISA 004 1% TFV gel trial. Baseline cervicovaginal lavage specimens collected from 737 HIV-uninfected women were analysed to determine the prevalence of HPV infection. Clinical, reproductive, demographic and behavioral data were captured. The presence of DNA from 37 HPV genotypes was assessed using Linear Array, and the concentrations of 48 relevant cytokines were quantified by multiplexed ELISA assays. The presence of HIV was measured monthly using two rapid tests and confirmed by western blot and PCR. Of the 737 eligible participants, 74% had prevalent HPV-infection (95% CI: 71–77%). Participants with prevalent HPV infection were 2.8 times more likely to acquire HIV infection compared to those with no HPV infection (95% CI: 1.3–5.9; p = 0.007). HIV risk was independent of the oncogenicity of HPV strains at baseline [(HPV oncogenic strains HR 2.5 (95% CI 1.0–6.2) vs non-oncogenic strains HR 2.1 (95% CI 0.9–5.1)], and was also increased in the presence of multiple concurrent infections (HR 3.1; 95% CI 1.4–6.8). No cytokine signatures were associated with prevalent HPV infection. The use of tenofovir gel did not prevent HPV infection. These data confirm a relationship between HPV infection and increased risk for HIV acquisition, and underscores the need to define the underlying biological mechanisms to inform targeted interventions in settings that bear a high burden of both infections.
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Genital tenofovir concentrations correlate with protection against HIV infection in the CAPRISA 004 trial: Importance of adherence for microbicide effectiveness
Journal of acquired immune deficiency syndromes (1999), 2015Co-Authors: Tanuja N. Gengiah, Quarraisha Abdool Karim, Lise. Werner, Kuo-hsiung. Yang, Nicole White, Salim S. Abdool KarimAbstract:OBJECTIVE: The CAPRISA 004 trial showed that coitally dosed tenofovir 1% gel reduced HIV acquisition by 39% overall and 54% when used consistently. The objective of this analysis was to ascertain its pharmacokinetic-pharmacodynamic relationship to protect against HIV acquisition. DESIGN: Genital and systemic tenofovir concentrations in 34 women who acquired HIV (cases) were compared with 302 randomly selected women who remained HIV uninfected (controls) during the CAPRISA 004 trial. In total 336 cervicovaginal fluid (CVF) 55 plasma and 23 paired cervical and vaginal tissue samples were assayed by validated methods for tenofovir and tenofovir diphosphate (tenofovir-DP) detection. RESULTS: Tenofovir was detected in the genital tract in 8 (23.5%) cases and 119 (39.4%) controls (P = 0.076). Among those with detectable genital tract tenofovir the median CVF concentrations were 97% lower in cases compared with controls 476 versus 13821 ng/mL (P = 0.107). A total of 14.7% (5/34) of cases and 32.8% (99/302) of controls were found to have tenofovir CVF concentrations above 100 ng/mL [odds ratio (OR): 0.35 P = 0.037]. At a higher threshold 8.8% (3/34) of cases and 26.2% (79/302) of controls were found to have tenofovir CVF concentrations above 1000 ng/mL (OR: 0.27 P = 0.036). Plasma tenofovir concentrations were /=100 ng/mL in CVF was associated with 65% (95% CI: 6% to 87%) protection against HIV whereas a >/=1000 ng/mL concentration correlated with 76% (95% CI: 8% to 92%) protection against HIV infection.
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Measuring Adherence by Visual Inspection of Returned Empty Gel Applicators in the CAPRISA 004 Microbicide Trial
AIDS and Behavior, 2014Co-Authors: Tanuja N. Gengiah, Quarraisha Abdool Karim, Leila E Mansoor, Nonhlanhla Yende-zuma, Michele Upfold, Anushka Naidoo, Salim S. Abdool KarimAbstract:In the CAPRISA 004 trial, adherence was estimated as the proportion of reported sex acts covered by two gel doses, which was assessed by counting returned empty gel applicators. The returned empty applicators were inspected visually in a standardized manner for residue on the outside of the applicator, as an indicator of vaginal insertion. Over 15 months, spanning 11,839 study visits by 838 women, a total of 59,800 returned empty applicators were inspected. By visual assessment, 77.5 % of these applicators appeared to have been inserted. To test the accuracy of the assessment we fitted a Cox model and found that the risk for HIV infection was doubled when less than half of the returned empty applicators had been assessed as not inserted in the vagina. Visual inspection enhanced both the accuracy of the adherence measurement and aided identification of mechanical problems with applicator use experienced by women in the trial.
Lise. Werner - One of the best experts on this subject based on the ideXlab platform.
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tenofovir gel for the prevention of herpes simplex virus type 2 infection
The New England Journal of Medicine, 2015Co-Authors: Quarraisha Abdool Karim, Cheryl Baxter, Ayesha B. M. Kharsany, Anna Christina. Grobler, Salim Abdool S Karim, Lise. WernerAbstract:BACKGROUND Globally, herpes simplex virus type 2 (HSV-2) infection is the most common cause of genital ulcer disease. Effective prevention strategies for HSV-2 infection are needed to achieve the goals of the World Health Organization global strategy for the prevention and control of sexually transmitted infections. METHODS We assessed the effectiveness of pericoital tenofovir gel, an antiviral microbicide, in preventing HSV-2 acquisition in a subgroup of 422 HSV-2–negative women enrolled in the Centre for the AIDS Programme of Research in South Africa (CAPRISA) 004 study, a double-blind, randomized, placebo-controlled trial. Incident HSV-2 cases were identified by evidence of seroconversion on an HSV-2 IgG enzyme-linked immunosorbent assay between study enrollment and exit. A confirmatory analysis was performed by Western blot testing. RESULTS The HSV-2 incidence rate was 10.2 cases per 100 person-years (95% confidence interval [CI], 6.8 to 14.7) among 202 women assigned to tenofovir gel, as compared with 21.0 cases per 100 person-years (95% CI, 16.0 to 27.2) among 222 women assigned to placebo gel (incidence rate ratio, 0.49; 95% CI, 0.30 to 0.77; P = 0.003). The HSV-2 incidence rate among the 25 women with vaginal tenofovir concentrations of 10,000 ng per milliliter or more was 5.7 cases per 100 person-years, as compared with 15.5 cases per 100 person-years among the 103 women with no detectable vaginal tenofovir (incidence rate ratio, 0.37; 95% CI, 0.04 to 1.51; P = 0.14). As confirmed by Western blot testing, there were 16 HSV-2 seroconversions among women assigned to tenofovir gel as compared with 36 among those assigned to the placebo gel (incidence rate ratio, 0.45; 95% CI, 0.23 to 0.82; P = 0.005). CONCLUSIONS In this study in South Africa, pericoital application of tenofovir gel reduced HSV-2 acquisition in women. (Funded by the U.S. Agency for International Development and others; ClinicalTrials.gov number, NCT00441298.)
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Genital tenofovir concentrations correlate with protection against HIV infection in the CAPRISA 004 trial: Importance of adherence for microbicide effectiveness
Journal of acquired immune deficiency syndromes (1999), 2015Co-Authors: Tanuja N. Gengiah, Quarraisha Abdool Karim, Lise. Werner, Kuo-hsiung. Yang, Nicole White, Salim S. Abdool KarimAbstract:OBJECTIVE: The CAPRISA 004 trial showed that coitally dosed tenofovir 1% gel reduced HIV acquisition by 39% overall and 54% when used consistently. The objective of this analysis was to ascertain its pharmacokinetic-pharmacodynamic relationship to protect against HIV acquisition. DESIGN: Genital and systemic tenofovir concentrations in 34 women who acquired HIV (cases) were compared with 302 randomly selected women who remained HIV uninfected (controls) during the CAPRISA 004 trial. In total 336 cervicovaginal fluid (CVF) 55 plasma and 23 paired cervical and vaginal tissue samples were assayed by validated methods for tenofovir and tenofovir diphosphate (tenofovir-DP) detection. RESULTS: Tenofovir was detected in the genital tract in 8 (23.5%) cases and 119 (39.4%) controls (P = 0.076). Among those with detectable genital tract tenofovir the median CVF concentrations were 97% lower in cases compared with controls 476 versus 13821 ng/mL (P = 0.107). A total of 14.7% (5/34) of cases and 32.8% (99/302) of controls were found to have tenofovir CVF concentrations above 100 ng/mL [odds ratio (OR): 0.35 P = 0.037]. At a higher threshold 8.8% (3/34) of cases and 26.2% (79/302) of controls were found to have tenofovir CVF concentrations above 1000 ng/mL (OR: 0.27 P = 0.036). Plasma tenofovir concentrations were /=100 ng/mL in CVF was associated with 65% (95% CI: 6% to 87%) protection against HIV whereas a >/=1000 ng/mL concentration correlated with 76% (95% CI: 8% to 92%) protection against HIV infection.
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HIV disease progression in seroconvertors from the CAPRISA 004 tenofovir gel pre-exposure prophylaxis trial.
Journal of acquired immune deficiency syndromes (1999), 2015Co-Authors: Nigel Garrett, Sengeziwe Sibeko, Lise. Werner, Carolyn Williamson, Nivashnee Naicker, Vivek Naranbhai, Natasha Samsunder, Clive M. Gray, Lynn Morris, Quarraisha Abdool KarimAbstract:Background While antiretroviral pre-exposure prophylaxis (PrEP) prevents HIV acquisition, it is not known if it alters HIV disease progression. This study assesses whether tenofovir gel impacted on disease progression among CAPRISA 004 microbicide trial seroconvertors.
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Impact of an Adherence Intervention on the Effectiveness of Tenofovir Gel in the CAPRISA 004 Trial
AIDS and Behavior, 2014Co-Authors: Leila Essop Mansoor, Quarraisha Abdool Karim, Lise. Werner, Bernadette T. Madlala, Nelisiwe Ngcobo, Deborah H. Cornman, K. Rivet Amico, Jeffrey Fisher, William A. Fisher, Kathleen M. MacqueenAbstract:High adherence is important in microbicide trials, but no adherence interventions to date have demonstrated empiric improvements in microbicide adherence or effectiveness. Approximately midway during the CAPRISA 004 trial, we implemented a novel adherence intervention (Adherence Support Program—ASP), based on an Information–Motivation–Behavioral Skills model and incorporating a Motivational Interviewing approach. We assessed the impact of the ASP on adherence and tenofovir gel effectiveness using a before-and-after comparison. Of the 889 women in the trial, 774 contributed 486.1 women-years of follow-up pre-ASP and 828 contributed 845.7 women-years of follow-up post-ASP. Median adherence rose from 53.6 % pre-ASP to 66.5 % post-ASP. Detectable tenofovir levels increased from 40.6 % pre-ASP to 62.5 % post-ASP in 64 women who had paired tenofovir drug samples. Gel effectiveness improved post-ASP; HIV incidence in the tenofovir gel arm was 24 % lower pre-ASP compared to 47 % lower post-ASP. Following implementation of the ASP, microbicide adherence improved with a concomitant increase in the effectiveness of tenofovir gel.
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The preventive misconception: experiences from CAPRISA 004.
AIDS and behavior, 2014Co-Authors: Rachael C. Dellar, Quarraisha Abdool Karim, Leila E Mansoor, Lise. Werner, Anna Christina. Grobler, Hilton Humphries, Fanelesibonge Ntombela, Londiwe. Luthuli, Salim S. Abdool KarimAbstract:Overestimating personal protection afforded by participation in a preventive trial, e.g. harboring a “preventive misconception” (PM), raises theoretical ethical concerns about the adequacy of the informed consent process, behavioral disinhibition, and adherence to prevention interventions. Data from the CAPRISA 004 1 % tenofovir gel trial were utilized to empirically evaluate these concerns. We found it necessary to re-think the current definition of PM during evaluation to distinguish between true misconception and reasonable inferences of protection based on increased access to evidence-based prevention interventions and/or clinical care. There was a significant association between PM and decreased condom use (p < 0.0001) and between PM and likelihood to present with an STI symptom (p = 0.023). There was, however, limited evidence in support of PM representing a lack of meaningful informed consent, or to suggest that it impacts adherence. Moreover, considering current insufficiencies in female-initiated HIV prevention interventions, PM is perhaps of limited concern in microbicide trials.
Salim Abdool S Karim - One of the best experts on this subject based on the ideXlab platform.
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tenofovir gel for the prevention of herpes simplex virus type 2 infection
The New England Journal of Medicine, 2015Co-Authors: Quarraisha Abdool Karim, Cheryl Baxter, Ayesha B. M. Kharsany, Anna Christina. Grobler, Salim Abdool S Karim, Lise. WernerAbstract:BACKGROUND Globally, herpes simplex virus type 2 (HSV-2) infection is the most common cause of genital ulcer disease. Effective prevention strategies for HSV-2 infection are needed to achieve the goals of the World Health Organization global strategy for the prevention and control of sexually transmitted infections. METHODS We assessed the effectiveness of pericoital tenofovir gel, an antiviral microbicide, in preventing HSV-2 acquisition in a subgroup of 422 HSV-2–negative women enrolled in the Centre for the AIDS Programme of Research in South Africa (CAPRISA) 004 study, a double-blind, randomized, placebo-controlled trial. Incident HSV-2 cases were identified by evidence of seroconversion on an HSV-2 IgG enzyme-linked immunosorbent assay between study enrollment and exit. A confirmatory analysis was performed by Western blot testing. RESULTS The HSV-2 incidence rate was 10.2 cases per 100 person-years (95% confidence interval [CI], 6.8 to 14.7) among 202 women assigned to tenofovir gel, as compared with 21.0 cases per 100 person-years (95% CI, 16.0 to 27.2) among 222 women assigned to placebo gel (incidence rate ratio, 0.49; 95% CI, 0.30 to 0.77; P = 0.003). The HSV-2 incidence rate among the 25 women with vaginal tenofovir concentrations of 10,000 ng per milliliter or more was 5.7 cases per 100 person-years, as compared with 15.5 cases per 100 person-years among the 103 women with no detectable vaginal tenofovir (incidence rate ratio, 0.37; 95% CI, 0.04 to 1.51; P = 0.14). As confirmed by Western blot testing, there were 16 HSV-2 seroconversions among women assigned to tenofovir gel as compared with 36 among those assigned to the placebo gel (incidence rate ratio, 0.45; 95% CI, 0.23 to 0.82; P = 0.005). CONCLUSIONS In this study in South Africa, pericoital application of tenofovir gel reduced HSV-2 acquisition in women. (Funded by the U.S. Agency for International Development and others; ClinicalTrials.gov number, NCT00441298.)
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trial participation disclosure and gel use behavior in the CAPRISA 004 tenofovir gel trial
Aids Care-psychological and Socio-medical Aspects of Aids\ hiv, 2014Co-Authors: Quarraisha Abdool Karim, Kathleen M. Macqueen, Francois Loggerenberg, Stacey Succop, Nelisle Majola, Nelisile Majola, Salim Abdool S KarimAbstract:Disclosure, or open communication, by female microbicide trial participants of their trial participation and use of an investigational HIV prevention drug to a sexual partner may affect participants' trial product usage behavior and contribute to poor adherence. With mixed results from recent microbicide clinical trials being linked to differing participant adherence, insights into the communication dynamics between trial participants and their sexual partners are particularly important. We examined the quantitative association between (1) communication of trial participation to a partner and participant adherence to gel and (2) communication of trial participation to a partner and participant HIV status. An in-depth adherence and product acceptability assessment was administered to the women participating in the CAPRISA 004 trial. Additionally, we collected qualitative data related to communication of trial participation and gel use. Qualitatively, among 165 women who had reported that they had discussed trial participation with others, most (68%) stated that they communicated participation to their sexual partner. Most of the women who had communicated study participation with their partners had received a positive/neutral response from their partner. Some of these women stated that gel use was easy; only a small number said that gel use was difficult. Among women who did not communicate their study participation to their partners, difficulty with gel use was more common and some women stated that they feared communicating their participation. Quantitatively, there was no statistically significant difference in the proportions of women who had communicated study participation to a partner across different adherence levels or HIV status. A deeper knowledge of the dynamics surrounding trial participation communication to male partners will be critical to understanding the spectrum of trial product usage behavior, and ultimately to designing tailored strategies to assist trial participants with product adherence.
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drug concentrations after topical and oral antiretroviral pre exposure prophylaxis implications for hiv prevention in women
The Lancet, 2011Co-Authors: Salim Abdool S Karim, Quarraisha Abdool Karim, Lise. WernerAbstract:The early closure of a clinical trial assessing the effectiveness of oral antiretroviral pre-exposure prophylaxis (PrEP) in women, FEM-PrEP,1 is a substantial setback for HIV prevention. Expectations of this trial were high in view of favourable results from the pre-exposure prophylaxis initiative (iPrEX) trial,2 which studied the same drug and dosing strategy in men who have sex with men, and the Centre for the AIDS Programme of Research in South Africa (CAPRISA 004) trial,3 which tested tenofovir gel (a topical PrEP formulation) in heterosexual women. As a result, the interim FEM-PrEP trial results, announced on April 18, 2011, which showed no protection against HIV infection,1 were disappointing. Using publicly available information1 and data from other PrEP studies, we offer a potential explanation for the results of the FEM-PrEP trial.
Sengeziwe Sibeko - One of the best experts on this subject based on the ideXlab platform.
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HIV disease progression in seroconvertors from the CAPRISA 004 tenofovir gel pre-exposure prophylaxis trial.
Journal of acquired immune deficiency syndromes (1999), 2015Co-Authors: Nigel Garrett, Sengeziwe Sibeko, Lise. Werner, Carolyn Williamson, Nivashnee Naicker, Vivek Naranbhai, Natasha Samsunder, Clive M. Gray, Lynn Morris, Quarraisha Abdool KarimAbstract:Background While antiretroviral pre-exposure prophylaxis (PrEP) prevents HIV acquisition, it is not known if it alters HIV disease progression. This study assesses whether tenofovir gel impacted on disease progression among CAPRISA 004 microbicide trial seroconvertors.
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Sensitive Tenofovir Resistance Screening of HIV-1 from the Genital and Blood Compartments of Women with Breakthrough Infections in the CAPRISA 004 Tenofovir Gel Trial
The Journal of infectious diseases, 2014Co-Authors: Xierong Wei, Quarraisha Abdool Karim, Sengeziwe Sibeko, Salim S. Abdool Karim, Lise. Werner, Vivek Naranbhai, Gillian Hunt, Jo Ann S. PassmoreAbstract:The Centre for the AIDS Programme of Research in South Africa 004 (CAPRISA 004) study demonstrated that vaginally applied tenofovir gel is a promising intervention for protecting women from sexually acquiring human immunodeficiency virus (HIV). However, the potential for emergence of tenofovir resistance remains a concern in women who seroconvert while using the gel despite the lack of plasma virus resistance as assessed by population sequencing during the trial. We applied highly sensitive polymerase chain reaction–based assays to screen for tenofovir resistance in plasma and vaginal swab specimens. The absence of mutation detection suggested little immediate risk of tenofovir-resistant HIV-1 emergence and forward transmission in settings in which gel users are closely monitored for HIV seroconversion.
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Women with Pregnancies Had Lower Adherence to 1% Tenofovir Vaginal Gel as HIV Preexposure Prophylaxis in CAPRISA 004, a Phase IIB Randomized-Controlled Trial
PloS one, 2013Co-Authors: Lynn T. Matthews, Sengeziwe Sibeko, Leila E Mansoor, Nonhlanhla Yende-zuma, David R. Bangsberg, Quarraisha Abdool KarimAbstract:Background: Antiretroviral prophylaxis may be a critical strategy to reduce periconception HIV transmission. Maximizing the benefit of periconception pharmacologic HIV risk-reduction requires an understanding of the links between pregnancy and adherence to this prevention strategy. Methods: We assessed study gel adherence among women with pregnancies compared to women without pregnancies enrolled in the CAPRISA 004 phase IIB trial of 1% vaginal tenofovir gel. Pregnancy was assessed with monthly urine tests. Adherence was measured monthly and defined as proportion of sex acts covered by two returned, used applicators based on pre- and post-coital dosing. High adherence was defined as a median adherence score of .80%, that is, more than 80% of sex acts were covered by two applications of study gel. A multivariate generalized estimating equations (GEE) model with a binomial distribution was used to assess covariates associated with high adherence (.80%) over time. Median adherence before and after pregnancy was compared using Wilcoxon signed rank test. Results: Among 868 women, 53 had at least 1 pregnancy (4.06 per 100 woman years, 95% CI: 3.04, 5.31). Women with pregnancies had lower median adherence compared to women without pregnancies (50% [IQR: 45–83] vs. 60% [IQR: 50– 100], p=0.02). Women with pregnancies also had a 48% lower odds of high adherence compared to women without pregnancies when adjusting for confounders (aOR 0.52, 95%CI: 0.41–0.66, p,0.0001). Among women with pregnancies, adherence before and after pregnancy was not different (50% [IQR: 46–83] vs. 55% [IQR: 20–100], p=0.68). Conclusions: Women with pregnancies were less likely to have high adherence to study gel compared to women without pregnancies. Understanding these differences may inform findings from HIV prevention trials and future implementation of antiretroviral prophylaxis for at-risk women who choose to conceive. The protocol for the parent trial is registered on ClinicalTrials.gov, NCT00441298, http://www.clinicaltrials.gov/ct2/show/NCT00441298.
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Safety of tenofovir gel, a vaginal microbicide, in South African women: results of the CAPRISA 004 Trial.
Antiviral therapy, 2012Co-Authors: David C. Sokal, Quarraisha Abdool Karim, Janet A. Frohlich, Cheryl Baxter, Sengeziwe Sibeko, Leila E Mansoor, Ayesha B. M. Kharsany, Anna Christina. Grobler, Nonhlanhla. Yende Zuma, Nomsa. MiyaAbstract:BACKGROUND Tenofovir gel, used vaginally before and after coitus, reduced women's acquisition of HIV by 39%. This is a safety assessment of tenofovir gel, including renal, bone, gastrointestinal, genital and haematological parameters. METHODS In the Centre for the AIDS Programme of Research in South Africa (CAPRISA) 004, a double-blind, randomized placebo-controlled trial, 445 of the 889 eligibly enrolled women were assigned to tenofovir gel. All participants were advised to use the gel vaginally only, with one dose of gel within 12 h before and a second dose as soon as possible after sex, with no more than two doses in 24 h. Clinical and laboratory safety data were collected at monthly and quarterly visits, respectively. Genital assessments were undertaken at enrolment and quarterly thereafter, or as indicated. RESULTS Women assigned to tenofovir gel were exposed to an average monthly vaginal dose of 240 mg of tenofovir (six applications). In total, six women, three in each group, had mild creatinine elevations, all of which occurred in July/August 2008. The incidence of anaemia was 3.5 and 3.8 per 100 women-years in tenofovir and placebo groups, respectively (P=0.80). Of the six women (four tenofovir and two placebo) experiencing bone fractures, none were associated with abnormal phosphate or calcium values. The proportion of women with diarrhoea was higher in the tenofovir gel group (17% versus 11%; P=0.026). There was no significant increase of any genital adverse event in the tenofovir group. CONCLUSIONS No significant renal, haematological, genital or bone effects were associated with the use of tenofovir gel. Aside from a puzzling increase in diarrhoea, tenofovir gel has an excellent safety profile.
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Preservation HIV-1-specific IFNγ+ CD4+ T-cell responses in breakthrough infections after exposure to tenofovir gel in the CAPRISA 004 microbicide trial.
Journal of acquired immune deficiency syndromes (1999), 2012Co-Authors: Quarraisha Abdool Karim, Sengeziwe Sibeko, Salim S. Abdool Karim, Lise. Werner, Vivek Naranbhai, Marianne W. Mureithi, Danielle Poole, Shabashini Reddy, Nompumelelo Mkhwanazi, Thumbi NdungʼuAbstract:The Centre for the AIDS Program of Research in South Africa 004 trial demonstrated reduction of sexual HIV-1 acquisition in women using a vaginal microbicide containing tenofovir. A better understanding of the consequences of antiretroviral-containing microbicides for immune responses in individuals with intercurrent HIV-1 infection is needed for future trials combining the use of microbicides with HIV-1 vaccines. Investigation of immune responses in women who acquired HIV-1 although using tenofovir gel showed significantly higher (P = 0.01) Gag-specific IFNγ+ CD4+ T-cell responses. The use of tenofovir-containing gel around the time of infection can modulate HIV-1 immunity, and these immunological changes need to be considered in future trials combining vaccines and microbicides.
