Setshaba Research Center

Pretoria, South Africa

Setshaba Research Center

Pretoria, South Africa

Time filter

Source Type

Agot K.,Impact Research and Development Organization | Ahmed K.,Setshaba Research Center | Odhiambo J.,Impact Research and Development Organization | Skhosana J.,Setshaba Research Center
Culture, Health and Sexuality | Year: 2016

Oral pre-exposure prophylaxis (PrEP) using the antiretroviral drug emtricitabine/tenofovir disoproxil fumarate (Truvada) has been shown to dramatically reduce the risk of HIV acquisition for women at higher risk of infection if taken daily. Understanding when and why women would intentionally stop using an efficacious oral PrEP drug within the context of their ‘normal’ daily lives is essential for delivering effective PrEP risk-reduction counselling. As part of a larger study, we conducted 60 qualitative interviews with women at higher risk of HIV in Bondo, Kenya, and Pretoria, South Africa. Participants charted their sexual contacts over the previous six months, indicated whether they would have taken PrEP if available and discussed whether and why they would have suspended PrEP use. Nearly all participants said they would have used PrEP in the previous six months; half indicated they would have suspended PrEP use at some point. Participants’ reasons for an extended break from PrEP were related to partnership dynamics (e.g., perceived low risk of a stable partner) and phases of life (e.g., trying to conceive). Life events (e.g., holidays and travel) could prompt shorter breaks in PrEP use. These circumstances may or may not correspond to actual contexts of lower risk, highlighting the importance of tailored PrEP risk-reduction counselling. © 2016 Informa UK Limited, trading as Taylor & Francis Group


Wang M.,FHI | Taylor D.,FHI | Ahmed K.,Setshaba Research Center | Agot K.,Impact Research and Development Organization | And 5 more authors.
Journal of Acquired Immune Deficiency Syndromes | Year: 2014

Background: Several clinical trials have demonstrated the safety and effectiveness of oral tenofovir disoproxil fumarate (TDF), with or without emtricitabine (FTC), as pre-exposure prophylaxis (PrEP) for reducing the risk of HIV acquisition. Adherence to the study product was insufficient to demonstrate the effectiveness of FTC/TDF in 2 PrEP clinical trials conducted among women (FEM-PrEP and the Vaginal and Oral Interventions to Control the Epidemic study), but further analyses of adherence in these studies may inform PrEP demonstration projects and future HIV prevention clinical trials. Methods: We randomly selected a subcohort of 150 participants randomized to FTC/TDF in 3 FEM-PrEP sites (Bondo, Kenya; Bloemfontein, South Africa; and Pretoria, South Africa) to examine adherence levels over time and to assess factors associated with adherence, based on plasma tenofovir and intracellular tenofovir diphosphate drug concentrations in specimens collected at 4-week visit intervals. Results: We observed drug concentrations consistent with good adherence in 28.5% of all visit intervals when drug was available to use, but only 12% of participants achieved good adherence throughout their study participation. In multivariate analysis, the Bloemfontein site [odds ratio (OR):2.43; 95% confidence interval (CI):1.32 to 4.48] and liking the pill color (OR: 2.93; 95% CI: 1.18 to 7.27) were positively associated with good adherence, whereas using oral contraceptive pills at enrollment was negatively associated with good adherence (OR: 0.37; 95% CI: 0.18 to 0.74). Conclusions: Most participants did not regularly adhere to the study product throughout their trial participation, although a smallminority did. Few factors associated with good adherence to the study product were identified in FEM-PrEP. Copyright © 2014 by Lippincott Williams & Wilkins.


Van Damme L.,FHI 360 | Corneli A.,FHI 360 | Ahmed K.,Setshaba Research Center | Agot K.,Impact Research and Development Organization | And 26 more authors.
New England Journal of Medicine | Year: 2012

BACKGROUND: Preexposure prophylaxis with antiretroviral drugs has been effective in the prevention of human immunodeficiency virus (HIV) infection in some trials but not in others. METHODS: In this randomized, double-blind, placebo-controlled trial, we assigned 2120 HIV-negative women in Kenya, South Africa, and Tanzania to receive either a combination of tenofovir disoproxil fumarate and emtricitabine (TDF-FTC) or placebo once daily. The primary objective was to assess the effectiveness of TDF-FTC in preventing HIV acquisition and to evaluate safety. RESULTS: HIV infections occurred in 33 women in the TDF-FTC group (incidence rate, 4.7 per 100 person-years) and in 35 in the placebo group (incidence rate, 5.0 per 100 person-years), for an estimated hazard ratio in the TDF-FTC group of 0.94 (95% confidence interval, 0.59 to 1.52; P = 0.81). The proportions of women with nausea, vomiting, or elevated alanine aminotransferase levels were significantly higher in the TDF-FTC group (P = 0.04, P<0.001, and P = 0.03, respectively). Rates of drug discontinuation because of hepatic or renal abnormalities were higher in the TDF-FTC group (4.7%) than in the placebo group (3.0%, P = 0.051). Less than 40% of the HIV-uninfected women in the TDF-FTC group had evidence of recent pill use at visits that were matched to the HIV-infection window for women with seroconversion. The study was stopped early, on April 18, 2011, because of lack of efficacy. CONCLUSIONS: Prophylaxis with TDF-FTC did not significantly reduce the rate of HIV infection and was associated with increased rates of side effects, as compared with placebo. Despite substantial counseling efforts, drug adherence appeared to be low. (Supported by the U.S. Agency for International Development and others; FEM-PrEP ClinicalTrials.gov number, NCT00625404.) Copyright © 2012 Massachusetts Medical Society.


Marais D.,University of Cape Town | Gawarecki D.,Population Council | Allan B.,University of Cape Town | Ahmed K.,Setshaba Research Center | And 7 more authors.
Antiviral Therapy | Year: 2011

Background: A randomised, double-blind, placebo-controlled trial found the vaginal microbicide Carraguard unable to prevent HIV infection. A substudy assessed the association of genital high-risk human papillomavirus (HR-HPV) in women at study end with Carraguard use. Methods: Participants received Carraguard gel or placebo plus condoms, and were instructed to use gel plus condoms during each act of vaginal intercourse. HR-HPV detection on cervical samples from 1,723 women was by Digene Hybrid Capture 2 analysis. Poisson regression analysis assessed the prevalence of genital HR-HPV for individuals receiving Carraguard relative to individuals receiving placebo. Results: In the Carraguard arm (n=875) the end trial unadjusted HR-HPV prevalence was 23.5% (95% CI 20.8-26.3) and 23.0% (95% CI 20.2-25.8) in placebo arm (n=843). Significant risk factors for HR-HPV infection were younger age, being single, an abnormal pap smear, multiple sexual partners and promiscuous behaviour without the use of a condom. There were 348 compliant women (174 Carraguard, 174 placebo users), with relatively high adherence to gel use, who inserted 80% of their opened, returned applicators of test product with the proportion of applicator insertions to sex acts >30%. After adjusting for risk factors, these compliant Carraguard users were 0.62 as likely to be classified HR-HPV positive (95% CI 0.41-0.94) as compliant placebo users. Conclusions: The prevalence of HR-HPV infection was lower in compliant Carraguard users than compliant placebo users. To our knowledge, this is the first report showing a negative association of HPV infection with a vaginal microbicide. ©2011 International Medical Press.


Corneli A.,Social and Behavioral Health science | Wang M.,Quantitative science | Agot K.,Impact Research and Development Organization | Ahmed K.,Setshaba Research Center | And 3 more authors.
Journal of Acquired Immune Deficiency Syndromes | Year: 2014

Background: FEM-PrEP was unable to demonstrate the effectiveness of oral emtricitabine/tenofovir disoproxil fumarate (FTC/TDF) as preexposure prophylaxis for HIV prevention because of low adherence. We hypothesized that one reason for the poor adherence was low perceived HIV risk. Methods: At enrollment and at quarterly follow-up visits, we assessed participants' perceived HIV risk for the subsequent 4 weeks. We used logistic regression to assess factors associated with some (small, moderate, or high) perceived HIV risk. We also used logistic regression with robust variance estimation to assess the association between risk perceptions (none versus some) reported at enrollment and at weeks 12, 24, and 36 and good adherence based on drug concentrations of plasma tenofovir and intracellular tenofovir diphosphate in specimens collected 4 weeks later (at weeks 4, 16, 28, and 40) among 150 randomly selected participants assigned FTC/TDF. Results: Multiple factors were statistically associated with having some perceived risk, including having sex without a condom, having multiple partners, and not knowing if a partner has HIV. We observed a significant association between having some risk perception and good adherence (odds ratio: 2.0; 95% confidence interval: 1.1 to 3.5; P = 0.016). Conclusions: Data suggest that participants are likely knowledgeable about factors that increase their HIV risk. Perceived risk seemed to have influenced some participants' decisions to adhere to the study pill within the context of a placebo-controlled clinical trial. Future research can explore the role of risk perception in the uptake of and adherence to pre-exposure prophylaxis, now that FTC/TDF has been shown efficacious. Copyright © 2014 by Lippincott Williams & Wilkins.


Grant R.M.,Gladstone | Grant R.M.,University of California at San Francisco | Liegler T.,University of California at San Francisco | Defechereux P.,Gladstone | And 11 more authors.
AIDS | Year: 2014

Background: Pre-exposure prophylaxis (PrEP) with daily oral emtricitabine (FTC)/ tenofovir disoproxil fumarate may select for drug resistance if there is low adherence. Methods: Plasma viral HIV-1 RNA level, CD4+ T-cell counts, and drug resistance were evaluated among seroconverting women in the FEM-PrEP trial (clinicaltrials.gov NCT00625404) using standard clinical tests, allele-specific PCR (ASPCR), and by deep sequencing. Tenofovir, FTC, and their intracellular metabolites were measured in plasma and cells. Results: There was no difference in plasma HIV-1 RNA level or CD4+ cell count among seroconverters in the active arm versus those receiving placebo. Tenofovir resistance was not observed. FTC resistance was detected using clinical assays in five seroconverters (four in the active arm and one in the placebo arm); two in the active arm occurred among women having moderate concentrations of PrEP drugs in the blood. The first evidence of infection occurred at the first postenrollment visit in three of the four with FTC resistance, although none had detectable viral nucleic acids at enrollment. FTC-resistant minor variants were detected in an additional four seroconverters (one in the active arm and three in the placebo arm). Conclusions: Drug resistance detected during ineffective PrEP use had characteristics suggesting transmitted infection or incubating infection prior to starting PrEP. Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.


Agot K.,Impact Research and Development Organization | Taylor D.,FHI 360 | Corneli A.L.,FHI 360 | Wang M.,FHI 360 | And 9 more authors.
AIDS and Behavior | Year: 2015

Oral emtricitabine/tenofovir disoproxil fumarate (FTC/TDF) has been evaluated as pre-exposure prophylaxis (PrEP). We describe the accuracy of self-reported adherence to FTC/TDF and pill counts when compared to drug concentrations in the FEM-PrEP trial. Using drug concentrations of plasma tenofovir (TFV) and intracellular tenofovir diphosphate (TFVdp) among a random sub-sample of 150 participants assigned to FTC/TDF, we estimated the positive predictive value (PPV) of four adherence measures. We also assessed factors associated with misreporting of adherence using multiple drug-concentration thresholds and explored pill use and misreporting using semi-structured interviews (SSIs). Reporting use of ≥1 pill in the previous 7 days had the highest PPV, while pill-count data consistent with missing ≤1 day had the lowest PPV. However, all four measures demonstrated poor PPV. Reported use of oral contraceptives (OR 2.26; p = 0.014) and weeks of time in the study (OR 1.02; p < 0.001) were significantly associated with misreporting adherence. Although most SSI participants said they did not misreport adherence, participant-dependent adherence measures were clearly unreliable in the FEM-PrEP trial. Pharmacokinetic monitoring remains the measure of choice until more reliable participant-dependent measures are developed. © 2014, The Author(s).


Corneli A.,Social and Behavioral Health science | Field S.,Biostatistics | Namey E.,Social and Behavioral Health science | Agot K.,Impact Research and Development Organization | And 4 more authors.
PLoS ONE | Year: 2015

Introduction: Several clinical trials have demonstrated the efficacy of pre-exposure prophylaxis (PrEP) in reducing HIV risk. One concern with introducing PrEP is whether users will engage in riskier sexual behaviors. Methods: We assessed the effect that PrEP may have on sexual risk behaviors by administering a survey to 799 women in Bondo, Kenya, and Pretoria, South Africa. Participants were asked about their sexual behavior intentions twice - once as if they were taking PrEP and once as if they were not taking PrEP - within four risk situations (vignettes). They responded using a 5-point ordinal scale. We used a series of linear mixed effects models with an unstructured residual covariance matrix to estimate the between- and within-subject differences in the mean likelihood of engaging in risky sexual behavior across the PrEP and non-PrEP contexts. We also calculated the total percentage of participants who reported a greater likelihood of engaging in risky sexual behavior if taking PrEP than if not taking PrEP, by vignette. Results: We found statistically significant differences in the mean likelihood of engaging in risky sexual behavior with the between-subject comparison (-0.17, p < 0.01) and with the within-subject comparison (-0.31, p < 0.001). Depending on the vignette, 27% to 40% of participants reported a greater likelihood of engaging in risky sexual behavior if taking PrEP than if not taking PrEP. Conclusions: Our findings indicate that modest increases in risky sexual behavior could occur with PrEP. Although responses from the majority of participants suggest they would not be more likely to engage in risky sexual behavior if they took PrEP, a substantial proportion might. Programs rolling out PrEP should be prepared to assist similar women in making informed choices about reducing their risk of HIV and about their sexual health beyond HIV prevention. © 2015 Corneli et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.


Corneli A.L.,Social and Behavioral Health science | McKenna K.,Social and Behavioral Health science | Perry B.,Social and Behavioral Health science | Ahmed K.,Setshaba Research Center | And 6 more authors.
Journal of Acquired Immune Deficiency Syndromes | Year: 2015

Background: FEM-PrEP was unable to determine whether once-daily, oral emtricitabine/tenofovir disoproxil fumarate reduces the risk of HIV acquisition among women because of low adherence. Self-reported adherence was high, and pill-count data suggested good adherence. Yet, drug concentrations revealed limited pill use. We conducted a follow-up study with former participants in Bondo, Kenya, and Pretoria, South Africa, to understand factors that had influenced overreporting of adherence and to learn the whereabouts of unused pills. Methods: Qualitative, semistructured interviews were conducted with 88 participants, and quantitative, audio computer-assisted self-interviews were conducted with 224 participants. We used thematic analysis and descriptive statistics to analyze the qualitative and quantitative data, respectively. Results: In audio computer-assisted self-interviews, 31% (n 70) said they had overreported adherence; the main reason was the belief that nonadherence would result in trial termination (69%, n 48). A considerable percentage (35%, n 78) acknowledged discarding unused pills. Few acknowledged giving their pills to someone else (4%, n 10), and even fewer acknowledged giving them to someone with HIV (2%, n 5). Many participants in the semistructured interviews said other participants had counted and removed pills from their bottles to appear adherent. Conclusions: Despite repeated messages that nonadherence would not upset staff, participants acknowledged several perceived negative consequences of reporting nonadherence, which made it difficult to report accurately. Uneasiness continued in the follow-up study, as many said they had not overreported during the trial. Efforts to improve self-reported measures should include identifying alternative methods for creating supportive environments that allow participants to feel comfortable reporting actual adherence. © 2015 Wolters Kluwer Health, Inc. All rights reserved.


Callahan R.,359 Blackwell Street | Nanda K.,359 Blackwell Street | Kapiga S.,Kilimanjaro Christian Medical Center | Malahleha M.,Setshaba Research Center | And 4 more authors.
Journal of Acquired Immune Deficiency Syndromes | Year: 2015

Pregnancy among study participants remains a challenge for trials of new HIV prevention agents despite promotion and provision of contraception. We evaluated contraceptive use, pregnancy incidence, and study drug adherence by contraceptive method among women enrolled in the FEM-PrEP trial of once-daily oral tenofovir disoproxil fumarate and emtricitabine (TDF-FTC) for HIV prevention. METHODS:: We required women to be using effective non-barrier contraception at enrollment. At each monthly follow-up visit, women were counseled on contraceptive use and tested for pregnancy. TDF-FTC adherence was determined by measuring plasma drug concentrations at 4-week intervals. We used Cox proportional hazards models to assess factors associated with incident pregnancy and multivariate logistic regression to examine the relationship between contraceptive method used at enrollment and TDF-FTC adherence. RESULTS:: More than half of women were not using effective contraception before enrollment. Ninety-eight percent of these women adopted either injectable (55%) or oral (43%) contraceptives. The overall pregnancy rate was 9.6 per 100 woman-years. Among injectable users and new users of combined oral contraceptives (COCs), the rates were 1.6 and 35.1, respectively. New users of injectables had significantly greater odds of adhering to TDF-FTC than new COC users [odds ratio (95% confidence interval): 4.4 (1.7 to 11.6), P = 0.002], existing COC users [3.1 (1.3 to 7.3), P = 0.01], and existing injectable users [2.4 (1.1 to 5.6), P = 0.04]. CONCLUSIONS:: Women using COCs during FEM-PrEP, particularly new adopters, were more likely to become pregnant and less likely to adhere to study product than injectable users. HIV prevention trials should consider requiring long-acting methods, including injectables, for study participation. © 2014 Wolters Kluwer Health, Inc.

Loading Setshaba Research Center collaborators
Loading Setshaba Research Center collaborators