Sarita Naidoo

Experiences in conducting multiple community-based HIV prevention trials among women in KwaZulu-Natal, South Africa

BackgroundSouth Africa, with its scientific capacity, good infrastructure and high HIV incidence rates, is ideally positioned to conduct large-scale HIV prevention trials. The HIV Prevention Research Unit of the South African Medical Research Council conducted four phase III and one phase IIb trials of women-initiated HIV prevention options in KwaZulu-Natal between 2003 and 2009. A total of 7046 women participated, with HIV prevalence between 25% and 45% and HIV incidence ranging from 4.5-9.1% per year. Unfortunately none of the interventions tested had any impact on reducing the risk of HIV acquisition; however, extremely valuable experience was gained, lessons learned and capacity built, while the communities gained associated benefits.ExperienceOur experience in conducting these trials ranged from setting up community partnerships to developing clinical research sites and dissemination of trial results. Community engagement included setting up community-based research sites with approval from both political and traditional leaders, and developing community advisory groups to assist with the research process. Community-wide education on HIV/sexually transmitted infection prevention, treatment and care was provided to over 90 000 individuals. Myths and misconceptions were addressed through methods such as anonymous suggestion boxes in clinic waiting areas and intensive education and counselling. Attempts were made to involve male partners to foster support and facilitate recruitment of women. Peer educator programmes were initiated to provide ongoing education and also to facilitate recruitment of women to the trials. Recruitment strategies such as door-to-door recruitment and community group meetings were initiated. Over 90% of women enrolled were retained.Community benefits from the trial included education on HIV prevention, treatment and care and provision of ancillary care (such as Pap smears, reproductive health care and referral for chronic illnesses). Social benefits included training of home-based caregivers and sustainable ongoing HIV prevention education through peer educator programmes.ChallengesSeveral challenges were encountered, including manipulation by participants of their eligibility criteria in order to enroll in the trial. Women attempted to co-enroll in multiple trials to benefit from financial reimbursements and individualised care. The trials became ethically challenging when participants refused to take up referrals for care due to stigma, denial of their HIV status and inadequate health infrastructure. Lack of disclosure of HIV status to partners and family members was particularly challenging. Some of the ethical dilemmas put to the test our responsibility as researchers and our obligation to provide health care to research participants.ConclusionConducting these five trials in a period of six years provided us with invaluable insights into trial implementation, community participation, recruitment and retention, provision of care and dissemination of trial results. The critical mass of scientists trained as clinical trialists will continue to address the relentless HIV epidemic in our setting and ensure our commitment to finding a biomedical HIV prevention option for women in the future.

Disclosure of pharmacokinetic drug results to understand nonadherence.

Objectives:In VOICE, a phase IIB trial of daily oral and vaginal tenofovir for HIV prevention, at least 50% of women receiving active products had undetectable tenofovir in all plasma samples tested. MTN-003D, an ancillary study using in-depth interviews (IDIs) and focus group discussions (FGDs), together with retrospective disclosure of plasma tenofovir pharmacokinetic results, explored adherence challenges during VOICE. Methods:We systematically recruited participants with pharmacokinetic data (median six plasma samples), categorized as low (0%, N = 79), inconsistent (1–74%, N = 28) or high (≥75%; N = 20) on the basis of frequency of tenofovir detection. Following disclosure of pharmacokinetic results, reactions were captured and adherence challenges systematically elicited; IDIs and FGDs were audio-recorded, transcribed, coded and thematically analysed. Results:We interviewed 127 participants from South Africa, Uganda and Zimbabwe. The most common reactions to pharmacokinetic results included surprise (41%; low pharmacokinetic), acceptance (39%; inconsistent pharmacokinetic) and happiness (65%; high pharmacokinetic). On the basis of participants’ explanations, we developed a typology of adherence patterns: noninitiation, discontinuation, misimplementation (resulting from visit-driven use, variable taking, modified dosing or regimen) and adherence. Fear of product side effects/harm was a frequent concern, fuelled by stories shared among participants. Although women with high pharmacokinetic levels reported similar concerns, several described strategies to overcome challenges. Women at all pharmacokinetic levels suggested real-time drug monitoring and feedback to improve adherence and reporting. Conclusion:Retrospective provision of pharmacokinetic results seemingly promoted candid discussions around nonadherence and study participation. The effect of real-time drug monitoring and feedback on adherence and accuracy of reporting should be evaluated in trials.

Characteristics of Women Enrolled into a Randomized Clinical Trial of Dapivirine Vaginal Ring for HIV-1 Prevention.

Introduction Women in sub-Saharan Africa are a priority population for evaluation of new biomedical HIV-1 prevention strategies. Antiretroviral pre-exposure prophylaxis is a promising prevention approach; however, clinical trials among young women using daily or coitally-dependent products have found low adherence. Antiretroviral-containing vaginal microbicide rings, which release medication over a month or longer, may reduce these adherence challenges. Methods ASPIRE (A Study to Prevent Infection with a Ring for Extended Use) is a phase III, randomized, double-blind, placebo-controlled trial testing the safety and effectiveness of a vaginal ring containing the non-nucleoside reverse transcriptase inhibitor dapivirine for prevention of HIV-1 infection. We describe the baseline characteristics of African women enrolled in the ASPIRE trial. Results Between August 2012 and June 2014, 5516 women were screened and 2629 HIV-1 seronegative women between 18–45 years of age were enrolled from 15 research sites in Malawi, South Africa, Uganda, and Zimbabwe. The median age was 26 years (IQR 22–31) and the majority (59%) were unmarried. Nearly 100% of participants reported having a primary sex partner in the prior three months but 43% did not know the HIV-1 status of their primary partner; 17% reported additional concurrent partners. Nearly two-thirds (64%) reported having disclosed to primary partners about planned vaginal ring use in the trial. Sexually transmitted infections were prevalent: 12% had Chlamydia trachomatis, 7% Trichomonas vaginalis, 4% Neisseria gonorrhoeae, and 1% syphilis. Conclusions African HIV-1 seronegative women at risk of HIV -1 infection were successfully enrolled into a phase III trial of dapivirine vaginal ring for HIV-1 prevention.

Prevalence and incidence of Trichomonas vaginalis infections in women participating in a clinical trial in Durban, South Africa

Background and objectives Trichomonas vaginalis is known to be the most common, curable, sexually transmitted infection among sexually active women and may be associated with the acquisition and transmission of HIV. The purpose of this analysis is to determine the prevalence and incidence of T vaginalis and assess risk factors associated with T vaginalis infection in a cohort of women participating in a clinical trial. Methods We analysed data from women participating in a phase III vaginal diaphragm trial conducted in two communities in Durban, South Africa from 2003 to 2006. A total of 3492 women were screened and 1485 women meeting the respective study eligibility criteria were enrolled. T vaginalis infection was determined at the initial screening visit and at quarterly visits among the enrolled women. Sexual behaviour and sociodemographic data were collected as per the study protocol. Combined data were analysed using STATA V.10.0. Results At baseline, prevalence of infection was 6.5%. The overall incident rate was estimated to be 8.6/100 women-years. Prevalent T vaginalis infection was associated with having a concurrent chlamydial infection and incident infections were associated with increased number of sex partners. Conclusions T vaginalis infection was found to be relatively high among this cohort of women. Given the association of this infection with HIV, there is an evident need for T vaginalis screening and treatment in populations at risk for both infections.

Research participants' skills development as HIV prevention peer educators in their communities.

This article describes the influence of a peer education programme on skills development among 22 women participating in HIV prevention trials. Interviews were used to collect data on peer educator experiences and their opinions of the trainings. The training enhanced their agency and confidence to engage their family and community on health promotion, including HIV prevention research procedures, thus improving their self-esteem and communication skills. Training and partnering with clinical trial participants as peer educators is an effective and sustainable community-based approach for HIV prevention.

Contraception use and impact on pregnancy prevention in women participating in an HIV prevention trial in South Africa

Background Unplanned pregnancy rates in South Africa are high. Effective use of contraception is therefore an essential public health intervention to prevent unplanned pregnancies. This study describes contraception use and its impact on pregnancy in women participating in HIV prevention research and its implications for public health practice. Method A secondary analysis of sociodemographic, behavioural, contraception use, and pregnancy incidence data was conducted amongst women participating in the Microbicides Development Programme (MDP) 301 trial conducted in Durban, South Africa. Log-rank tests were carried out to compare the pregnancy incidence between women who reported use of injectable contraceptive methods compared to women using oral contraceptive pills, using condoms and other methods (intrauterine device, traditional methods and natural methods). The effect of types of contraceptives on pregnancy incidence was assessed using Cox proportional hazards regression models. Results Of the 2018 women enrolled, injectable contraception was the most commonly used method (52%) compared to pills, condoms for pregnancy prevention and other methods. Injectable contraception use was associated with lower crude pregnancy incidence of 4.4 per 100 woman-years [95% confidence interval (95% CI 3.3–5.9)] compared to women using pills [19.3 per 100 woman-years (95% CI 13.3–28.0)], condoms [19.7 per 100 woman-years (95% CI 16.3–23.6)] and other methods [11.5 per 100 woman-years (95% CI 7.5–17.6)]. This effect remained significant when adjusted for age, level of education, condom use at last sex act [hazard ratio 0.27, (95% CI 0.16–0.47, p<0.001)]. Conclusion Injectable contraception offered a high level of protection against pregnancies among women in Durban. Trial registration number ISRCTN64716212.

Sharing of Investigational Drug Among Participants in the Voice Trial

AbstractProduct sharing among participants can impact on adherence and compromise the outcome in clinical trials. We describe incidents of product sharing at the Durban clinical research sites conducting the VOICE trial. The Durban sites enrolled 2750 women with 1103 and 1647 participants randomized to the vaginal gel and oral tablet arms respectively. Monthly pill and applicator counts including product assessments were conducted by pharmacists. Discrepancies with product counts prompted discussions with participants. Thirty-two cases of product sharing were identified. Vaginal gels were more commonly shared than oral tablets. Product sharing between study participants and their female friends or relatives living in the same household was identified as the most common source of product sharing in this analysis. Study product counts and pharmacist-driven discussions with participants may help to identify reasons for product sharing and inform the development of strategies for PrEP implementation outside of the research setting. ClinicalTrials.gov number: NCT00705679

Shared responsibility for ensuring appropriate management of incidental findings: a case study from South Africa

We report the case of an HIV prevention clinical trial participant who was referred to a local hospital for investigation and management of an incidental finding unrelated to her study participation. This case illustrates the complexities in the management of incidental findings within the context of clinical trials and highlights the importance of ethical oversight of trials. Trial registration number Protocol number ISRCTN64716212.