[Show abstract][Hide abstract] ABSTRACT: A major concern with using antiretroviral (ARV)-based products for HIV prevention is the potential spread of drug resistance, particularly from individuals who are HIV-infected but unaware of their status. Limited data exist on the prevalence of HIV infection or drug resistance among potential users of ARV-based prevention products.
A cross-sectional study of reproductive-aged women who presented to screen for an HIV prevention trial was conducted at 7 clinical sites in Durban, South Africa. CD4+T cell counts, HIV-1 RNA levels and population sequencing of the protease and reverse transcriptase genes were performed for all women with 2 positive HIV rapid tests. Resistance mutations were identified using the Stanford Calibrated Population Resistance Tool.
Of the 1073 evaluable women, 400(37%) were confirmed as HIV-infected. Of those, plasma HIV-1 RNA was detectable in 365/400(91%) and undetectable(<40 copies/ml) in 35/400(9%) women. 156 women(39%) were eligible for antiretroviral therapy (CD4+T cell counts<350 cells/mm(3)) and 50(13%) met criteria for AIDS(CD4<200 cells/mm(3)). Of 352 plasma samples(>200 copies/ml) analyzed for drug resistance, 26(7.4%) had nucleoside reverse transcriptase inhibitor (NRTI), non-nucleoside reverse transcriptase inhibitor (NNRTI) or protease inhibitor (PI) drug resistance mutations. Among those with resistance, 18/26 participants(62%) had single-class NNRTI resistance and 5/26(19%) had dual-class NRTI/NNRTI. Major mutations in reverse transcriptase included K65R(n = 1), L74I(n = 1), K103N(n = 19), V106M(n = 4), Y181C(n = 2), M184V(n = 4), and K219E/R(n = 2). Major PI-resistance mutations were rare: M46L(n = 1) and I85V(n = 1). All participants were infected with subtype C virus, except one infected with subtype A.
In women from Durban, South Africa screening for an HIV prevention trial, the HIV prevalence was high (37%) and HIV drug resistance prevalence was above 5%. This study highlights the potential challenges faced when implementing an ARV-based prevention product that overlaps with first-line antiretroviral therapy. Effective screening to exclude HIV infection among women interested in uptake of ARV-based HIV prevention will be essential in limiting the spread of ARV resistance.
PLoS ONE 04/2013; 8(4):59787-. · 3.53 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: OBJECTIVE:: To compare the two control arms of HPTN 035 (a hydroxyethylcellulose (HEC) gel control arm and a no gel control arm) to assess behavioral effects associated with gel use and direct causal effects of the HEC gel on STIs, pregnancy, and genital safety.Design: Randomized trial with one blinded (HEC gel) and one open label (no gel) control arms. METHODS:: HIV-uninfected, sexually active women were randomized into the HEC gel arm (n=771) and into the no gel arm (n=772) in five countries. Participants in the HEC gel arm were instructed to insert the study gel intravaginally <1 hour before each vaginal sex act. Data on sexual behavior, adherence, safety, pregnancy, and STIs were collected quarterly for 12 to 30 months of follow-up. RESULTS:: During follow-up, mean reported condom use in the past week was significantly higher in the no gel arm (81% versus 70%, p<0.001). There were no significant differences, after adjusting for this differential condom use, between the two arms in rates of genital safety events, pregnancy outcomes, or STIs, including HIV-1. CONCLUSIONS:: In this large randomized trial, we found no significant differences between the no gel and HEC gel arms in rates of genital safety events, pregnancy outcomes, or STIs. These results aid interpretation of the results of previous vaginal microbicide trials that used the HEC gel as a control. The HEC gel is suitable as a control for ongoing and future vaginal microbicide studies.
[Show abstract][Hide abstract] ABSTRACT: The majority of new HIV infections are acquired through heterosexual transmission. There is urgent need for prevention methods to compliment behavior change and condom use. Topical microbicide represent a potential strategy for reduction of HIV transmission in women.
Monthly Colposcopy evaluations were performed during pelvic examinations among 299 women enrolled in the Phase 2 portion of HPTN 035 study at four sites (1 in USA, 3 in Southern Africa). This was a phase 2/2b, multisite, randomized, and controlled clinical trial with four arms: BufferGel, 0.5% PRO2000 Gel, placebo gel and no gel. At two of the sites, pelvic examinations were conducted by the use of naked eye without colposcopy.
A colposcopy finding of any kind was detected in 48% of participants at baseline compared to 40% at 3 months (p =0.04). The lower rates were also observed in vaginal discharge (22% at baseline, 16% at 3 months, p=0.06), erythema (15% at baseline, 8% at 3 months, p=0.004). The trend towards significance at p=0.05 disappear when utilizing stringent statistical significance levels. A pelvic finding of any kind was detected in 71% of colposcopy participants compared to 41% of participants who had naked eye examination only conducted at two sites that performed both colposcopy and naked eye without colposcopy. Use of colposcopy yielded significantly higher rates of participants with deep epithelial disruption, erythema and ecchymosis. We observed no cases of incident Chlamydia, Gonorrhea, or Syphilis during the three month follow up. There were 2 cases of incident HIV during 3-month study period neither of which was associated with any abnormal colposcopy evaluation findings.
No safety signals were observed in the 4 study arms, allowing seamless transition from phase 2 to 2b. Colposcopy utility in microbicide clinical trials has minimal value given high rates of background noise findings of no relevant clinical significance.
Journal of the International AIDS Society 08/2012; 15(2):17376. · 4.21 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The province of KwaZulu-Natal has the highest prevalence of HIV in South Africa, particularly among young women. In order to more closely examine the HIV prevalence and incidence in non-pregnant women from rural, semi-rural and urban areas, data from 5,753 women screened for enrolment into three HIV prevention studies were combined and analysed. The prevalence of HIV infection was 43% at screening. HIV incidence among the 2,523 enrolled HIV-negative women was determined every quarter, and sexual behaviour and socio-demographic data were collected as per respective protocols. During follow-up, 211 women seroconverted (6.6/100 women years). Multivariate analysis found that seroconversion rates were highest among women who were ≤24 years old, single and not cohabiting, and who had incident sexually transmitted infections. The epidemic in KwaZulu-Natal calls for targeted HIV prevention interventions among those at highest risk of acquiring or transmitting infection.
AIDS and Behavior 09/2011; 16(7):2062-71. · 3.49 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To determine risk factors for sexually transmitted infections (STIs) among women in Durban and Hlabisa (South Africa), Moshi (Tanzania), and Lusaka (Zambia).
Between 2003 and 2004, 958 women at risk of STIs were enrolled in a 1-year prospective study. They were interviewed at each monthly visit, and samples for STI testing were collected during quarterly and other visits when clinically indicated.
The incidence of infections as measured in person-years at risk (PYAR) was as follows: overall trichomoniasis, 31.9/100 PYAR; chlamydial infection in South Africa, 19.5/100 PYAR; chlamydial infection in Tanzania and Zambia, 4.9/100 PYAR; gonorrhea in South Africa, 16.5/100 PYAR; gonorrhea in Tanzania and Zambia, 5.3/100 PYAR; overall syphilis, 7.5/100 PYAR; and overall HIV, 3.8/100 PYAR. The incidence of most STIs was highest among the South African sites, where chlamydial infection and gonorrhea were detected by using a more sensitive assay. Independent risk factors included age, hormonal contraceptive methods, and measures of sexual behavior, including number of sex partners and occurrence of anal sex in the past 3 months. Women with incident HIV infection were at increased risk of chlamydial infection [odds ratio (OR) = 5.5, 95% confidence interval (CI): 2.0-15.2]and gonorrhea (OR = 5.7, 95% CI: 1.9-17.0) in South African sites. Despite ongoing counseling during the study, high-risk sexual behaviors were common, and consistent condom use remained low.
The incidence of STIs, including HIV, was high among women in this study. These findings highlight the urgent need for effective HIV/STI prevention programs in this population.
[Show abstract][Hide abstract] ABSTRACT: To evaluate the preparedness for phase 2/IIb/III microbicide trials at 4 clinical trial sites: Durban and Hlabisa (South Africa), Lusaka (Zambia), and Moshi (Tanzania).
A prospective cohort study was undertaken to assess site suitability for microbicide efficacy studies. Study objectives included assessing sites' ability to recruit and retain high-risk women with the appropriate HIV incidence rates needed to conduct microbicide efficacy studies.
Nine hundred fifty-eight consenting women were enrolled and followed for up to 1 year. Demographic, behavioral, laboratory, and clinical data were collected to determine the incidence rates of HIV, sexually transmitted infections, and pregnancy.
Accrual was completed in 6.3, 6.7, 7.1, and 8.3 months in Durban, Hlabisa, Moshi, and Lusaka, respectively. The highest month 12 participant retention rate was recorded in Durban (97%), followed by Hlabisa (94%), Moshi (86%), and Lusaka (93%). Mean overall age of enrolled participants was 28.6 years (ranging from 27.0 to 32.2 years) across sites. Despite condom counseling, rates of condom use were slightly lower at study end. Pregnancy incidence in the study as a whole was 20.2 per 100 women-years (wy). Overall HIV prevalence was 32.5%, and overall HIV incidence was 3.8 per 100 wy (95% confidence interval [CI]: 2.6 to 5.2). HIV incidence per site was 5.3 per 100 wy in Durban (95% CI: 2.7 to 9.2), 6.2 per 100 wy in Hlabisa (95% CI: 3.4 to 10.5); 2.6 per 100 wy in Lusaka (95% CI: 1.0 to 5.8), and 1.4 per 100 wy in Moshi (95% CI: 0.3 to 4.0).
Preparatory studies provide accurate local estimates of HIV incidence, recruitment and retention rates, and behavioral characteristics of targeted populations for large-scale clinical trials. Determining these factors allows for better preparation for design, sample size, and appropriate population for future selection of trial sites. Because of the lower than expected HIV incidence observed at the Moshi site, only the South African and Zambian sites were selected for the phase 2/IIb trial.