Baseline Predictors of High Adherence to a Coitally Dependent Microbicide Gel Based on an Objective Marker of Use: Findings from the Carraguard Phase 3 Trial.

A randomized, placebo-controlled, efficacy trial of Carraguard was unable to demonstrate a reduction in women's risk of HIV infection, which may have been due, in part, to low adherence (gel used in 42 % of vaginal sex acts, on average). A secondary analysis was undertaken to understand baseline factors associated with high adherence (gel used in ≥85 % of sex acts). Women who reported ≥1 vaginal sex act, returned ≥1 opened applicator, and had ≥1 conclusive post-enrollment HIV test (N = 5990) were included. Adherence was estimated as the ratio of average weekly applicator insertions (based on a dye stain assay indicating vaginal insertion)/average weekly sex acts (by self-report). Multivariate logistic regression modeling indicated that coital frequency, site, contraception, and partner age difference had a significant impact on adherence. Women reporting >1 and ≤2 vaginal sex acts per week, on average, were half as likely to be adherent as those reporting 1 vaginal sex act per week or less [adjusted odds ratio (AOR): 0.48; 95 % CI 0.38-0.61]; women from the Western Cape had one-third the odds of being adherent compared to women from KZN (AOR: 0.31; 95 % CI 0.23-0.41); compared to women using injectable contraception, women using any other or no method were more likely to be adherent (AOR: 1.30; 95 % CI 1.04-1.63); and women who had a larger age gap from their partners were more likely to be adherent (AOR: 1.03; 95 % CI 1.01-1.05; p = 0.001). Despite low adherence, overall, 13 % of participants achieved nearly perfect adherence, indicating a potential niche for a coitally dependent microbicide. More research is needed on the impact of sexual patterns and HIV risk perception on product acceptability and adherence to improve counseling in ongoing trials and when products are eventually introduced.

Efficacy of Carraguard for prevention of HIV infection in women in South Africa: a randomised, double-blind, placebo-controlled trial.

BACKGROUND: Female-initiated HIV-prevention options, such as microbicides, are urgently needed. We assessed Carraguard, a carrageenan-based compound developed by the Population Council, for its efficacy and long-term safety in prevention of HIV infection in women. METHODS: We undertook a randomised, placebo-controlled, double-blind trial in three South African sites in sexually-active, HIV-negative women, aged 16 years and older. 6202 participants, who were randomly assigned by a block randomisation scheme to Carraguard (n=3103) or placebo (methylcellulose [n=3099]), were instructed to use one applicator of gel plus a condom during each vaginal sex act. Participants were followed up for up to 2 years. Visits every 3 months included testing for HIV presence and pregnancy, pelvic examinations, risk reduction counselling, and treatment for curable sexually transmitted infections and symptomatic vaginal infections. The primary outcome was time to HIV seroconversion. Analysis was in the efficacy population (a subset of the intention-to-treat population, excluding participants for whom efficacy could not be assessed). This study is registered with ClinicalTrials.gov, number NCT00213083. FINDINGS: For the primary outcome (time to HIV seroconversion) we analysed 3011 women in the Carraguard group and 2994 in the placebo group. HIV incidence was 3.3 per 100 woman-years (95% CI 2.8-3.9) in the Carraguard group (134 events) and 3.8 per 100 woman-years (95% CI 3.2-4.4) in the placebo group (151 events), with no significant difference in the distribution of time to seroconversion (p=0.30). The covariate-adjusted hazard ratio was 0.87 (95% CI 0.69-1.09). Rates of self-reported gel use (96.2% Carraguard, 95.9% placebo) and condom use (64.1% in both groups) at last sex acts were similar in both groups. On the basis of applicator testing, however, gel was estimated to have been used in only 42.1% of sex acts, on average (41.1% Carraguard, 43.1% placebo). 1420 (23%) women in the intention-to-treat population had adverse events (713 Carraguard, 707 placebo), and 95 (2%) women had adverse events that were related to gel use (48 Carraguard, 47 placebo). Serious adverse events occurred in 72 (2%) women in the Carraguard group and 78 (3%) in the placebo group, only one of which was considered possibly related to gel use (placebo group). INTERPRETATION: This study did not show Carraguard's efficacy in prevention of vaginal transmission of HIV. No safety concerns were recorded.

The effectiveness of Carraguard, a vaginal microbicide, in protecting women against high-risk human papillomavirus infection.

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.

Agreement between self- and clinician-collected specimen results for detection and typing of high-risk human papillomavirus in specimens from women in Gugulethu, South Africa.

We assessed the agreement in detection of high-risk human papillomavirus (HPV), as well as specific HPV types, between self- and clinician-obtained specimens for 450 women over 18 years of age attending a community health center in Gugulethu, South Africa. Both self-collected swabs and tampons had high agreement with clinician-obtained brushes when the Roche Reverse Line Blot Assay (RLBA) was used (for swabs, 86% concordance, with a kappa statistic [kappa] of 0.71; for tampons, 89% concordance, with kappa of 0.75). Agreement was lower, although still fair, with the Digene Hybrid Capture 2 test (HC2), with kappa higher for swabs than for tampons (for swabs, 81% concordance, with kappa of 0.61; for tampons, 82% concordance, with kappa of 0.55). Low-risk HPV types were nearly two times more common in self-collected specimens than in clinician-collected specimens tested by RLBA. All 15 women diagnosed with high-grade lesions by cytology tested positive for high-risk HPV with clinician-collected specimens tested by RLBA and HC2, while 11 out of 15 tested positive with self-collected specimens by HC2 and 5 out of 6 tested positive by RLBA. Self-collected specimens can provide valid specimens for HPV testing using nucleic acid amplification tests, although a few cytological abnormalities may be missed.

Two methods of self-sampling compared to clinician sampling to detect reproductive tract infections in Gugulethu, South Africa.

OBJECTIVES: To assess the validity, feasibility, and acceptability of 2 methods of self-sampling compared to clinician sampling during a speculum examination. GOAL: To improve screening for reproductive tract infections (RTIs) in resource-poor settings. STUDY DESIGN: In a public clinic in Cape Town, 450 women underwent a speculum examination and were randomized to self-sample with either a tampon or vaginal swabs. All specimens were tested for the same pathogens using the same diagnostic tests. RESULTS: Self-sampling resulted in satisfactory validity for N gonorrhoeae, C trachomatis, bacterial vaginosis, and Candida species (tampons and swabs) and high-risk human papillomavirus (swabs only) when tested with molecular tests or microscopy, but not for T vaginalis by culture. Self-sampling was feasible and acceptable, but some women preferred speculum examinations, which allow the clinician to view the vagina and cervix. CONCLUSIONS: Although self-sampling should not replace speculum examinations in all circumstances, it should be explored further as an RTI screening strategy.