Andrew Fullem

Safety and Tolerability of BufferGel, a Novel Vaginal Microbicide, in Women in the United States

BufferGel (ReProtect, LLC) is a vaginal gel with an acidic buffering action that was designed to prevent vaginal neutralization by semen. The purpose of this study was to evaluate the safety and tolerability of BufferGel (ReProtect, Limited Liability Company) applied vaginally either once or twice daily by 27 women who were at low risk for acquisition of human immunodeficiency virus (HIV). Participants initially used the product once daily for 14 days and then twice daily for 14 days; they underwent colposcopy before and after product exposure. BufferGel was well tolerated, although two-thirds of the participants reported at least 1 mild or moderate adverse experience. The most common adverse events were irritative genitourinary symptoms. Product use was discontinued after 3 adverse events. BufferGel was well tolerated in women at low risk for acquisition of HIV; toxicity was limited and occurred at frequencies similar to those in women who did not use any vaginal product and at levels lower than in women who used detergent-based microbicides.

phase 1 Trial of the Topical Microbicide Buffergel: Safety Results From Four International Sites

Aim: To evaluate the safety of BufferGel (ReProtect LLC, Baltimore, MD), a spermicidal microbicide that acidifies semen and maintains the protective acidity of the vagina, in a high‐dose tolerance trial. Methods: HIV/STD negative, sexually abstinent, and sexually active women in India, Thailand, Malawi, and Zimbabwe were asked to insert one applicator (˜5 ml) of BufferGel vaginally twice per day for 14 days. Sexually active women agreed to have sex (while using BufferGel and nonlubricated condoms) at least twice per week. Results: In total, 98 women (30 sexually abstinent and 68 sexually active) were enrolled. Overall compliance with product use was 93%. Epithelial abnormalities detected by pelvic examination or colposcopy were uncommon (8 cases in 271 examinations). Irritation was reported by approximately one quarter of the women (0.58 events per woman‐week) but was generally mild and of short duration. The prevalence of bacterial vaginosis (BV) fell significantly, from 30% at enrollment to 6% at one week, and 7% at two weeks of BufferGel use. Thirty‐two women acquired microscopically detectable yeast during BufferGel exposure, but only 3 developed symptomatic vaginitis. Conclusion: BufferGel appears to be safe and well tolerated by the cervicovaginal epithelium. Its effect on BV and yeasts merits further study.

HIV self-testing among female sex workers in Zambia: A cluster randomized controlled trial

Background HIV self-testing (HIVST) may play a role in addressing gaps in HIV testing coverage and as an entry point for HIV prevention services. We conducted a cluster randomized trial of 2 HIVST distribution mechanisms compared to the standard of care among female sex workers (FSWs) in Zambia. Methods and findings Trained peer educators in Kapiri Mposhi, Chirundu, and Livingstone, Zambia, each recruited 6 FSW participants. Peer educator–FSW groups were randomized to 1 of 3 arms: (1) delivery (direct distribution of an oral HIVST from the peer educator), (2) coupon (a coupon for collection of an oral HIVST from a health clinic/pharmacy), or (3) standard-of-care HIV testing. Participants in the 2 HIVST arms received 2 kits: 1 at baseline and 1 at 10 weeks. The primary outcome was any self-reported HIV testing in the past month at the 1- and 4-month visits, as HIVST can replace other types of HIV testing. Secondary outcomes included linkage to care, HIVST use in the HIVST arms, and adverse events. Participants completed questionnaires at 1 and 4 months following peer educator interventions. In all, 965 participants were enrolled between September 16 and October 12, 2016 (delivery, N = 316; coupon, N = 329; standard of care, N = 320); 20% had never tested for HIV. Overall HIV testing at 1 month was 94.9% in the delivery arm, 84.4% in the coupon arm, and 88.5% in the standard-of-care arm (delivery versus standard of care risk ratio [RR] = 1.07, 95% CI 0.99–1.15, P = 0.10; coupon versus standard of care RR = 0.95, 95% CI 0.86–1.05, P = 0.29; delivery versus coupon RR = 1.13, 95% CI 1.04–1.22, P = 0.005). Four-month rates were 84.1% for the delivery arm, 79.8% for the coupon arm, and 75.1% for the standard-of-care arm (delivery versus standard of care RR = 1.11, 95% CI 0.98–1.27, P = 0.11; coupon versus standard of care RR = 1.06, 95% CI 0.92–1.22, P = 0.42; delivery versus coupon RR = 1.05, 95% CI 0.94–1.18, P = 0.40). At 1 month, the majority of HIV tests were self-tests (88.4%). HIV self-test use was higher in the delivery arm compared to the coupon arm (RR = 1.14, 95% CI 1.05–1.23, P = 0.001) at 1 month, but there was no difference at 4 months. Among participants reporting a positive HIV test at 1 (N = 144) and 4 months (N = 235), linkage to care was non-significantly lower in the 2 HIVST arms compared to the standard-of-care arm. There were 4 instances of intimate partner violence related to study participation, 3 of which were related to HIV self-test use. Limitations include the self-reported nature of study outcomes and overall high uptake of HIV testing. Conclusions In this study among FSWs in Zambia, we found that HIVST was acceptable and accessible. However, HIVST may not substantially increase HIV cascade progression in contexts where overall testing and linkage are already high. Trial registration ClinicalTrials.gov NCT02827240

Zambian Peer Educators for HIV Self-Testing (ZEST) study: rationale and design of a cluster randomised trial of HIV self-testing among female sex workers in Zambia

Background HIV testing and knowledge of status are starting points for HIV treatment and prevention interventions. Among female sex workers (FSWs), HIV testing and status knowledge remain far from universal. HIV self-testing (HIVST) is an alternative to existing testing services for FSWs, but little evidence exists how it can be effectively and safely implemented. Here, we describe the rationale and design of a cluster randomised trial designed to inform implementation and scale-up of HIVST programmes for FSWs in Zambia. Methods The Zambian Peer Educators for HIV Self-Testing (ZEST) study is a 3-arm cluster randomised trial taking place in 3 towns in Zambia. Participants (N=900) are eligible if they are women who have exchanged sex for money or goods in the previous 1 month, are HIV negative or status unknown, have not tested for HIV in the previous 3 months, and are at least 18 years old. Participants are recruited by peer educators working in their communities. Participants are randomised to 1 of 3 arms: (1) direct distribution (in which they receive an HIVST from the peer educator directly); (2) fixed distribution (in which they receive a coupon with which to collect the HIVST from a drug store or health post) or (3) standard of care (referral to existing HIV testing services only, without any offer of HIVST). Participants are followed at 1 and 4 months following distribution of the first HIVST. The primary end point is HIV testing in the past month measured at the 1-month and 4-month visits. Ethics and dissemination This study was approved by the Institutional Review Boards at the Harvard T.H. Chan School of Public Health in Boston, USA and ERES Converge in Lusaka, Zambia. The findings of this trial will be presented at local, regional and international meetings and submitted to peer-reviewed journals for publication. Trial registration number Pre-results; NCT02827240.

Effect of HIV self-testing on the number of sexual partners among female sex workers in Zambia

Objectives: To assess the effect of two health system approaches to distribute HIV self-tests on the number of female sex workers’ client and nonclient sexual partners. Design: Cluster randomized controlled trial. Methods: Peer educators recruited 965 participants. Peer educator–participant groups were randomized 1 : 1 : 1 to one of three arms: delivery of HIV self-tests directly from a peer educator, free facility-based delivery of HIV self-tests in exchange for coupons, or referral to standard-of-care HIV testing. Participants in all three arms completed four peer educator intervention sessions, which included counseling and condom distribution. Participants were asked the average number of client partners they had per night at baseline, 1 and 4 months, and the number of nonclient partners they had in the past 12 months (at baseline) and in the past month (at 1 month and 4 months). Results: At 4 months, participants reported significantly fewer clients per night in the direct delivery arm (mean difference −0.78 clients, 95% CI −1.28 to −0.28, P = 0.002) and the coupon arm (−0.71, 95% CI −1.21 to −0.21, P = 0.005) compared with standard of care. Similarly, they reported fewer nonclient partners in the direct delivery arm (−3.19, 95% CI −5.18 to −1.21, P = 0.002) and in the coupon arm (−1.84, 95% CI −3.81 to 0.14, P = 0.07) arm compared with standard of care. Conclusion: Expansion of HIV self-testing may have positive behavioral effects enhancing other HIV prevention efforts among female sex workers in Zambia. Trial Registration: ClinicalTrials.gov NCT02827240.