HIV disease progression among women following seroconversion during a tenofovir-based HIV prevention trial.

CAPRISA, 2017.Abstract available in pdf

Long-term follow-up of HIV seroconverters in microbicide trials – rationale, study design, and challenges in MTN-015

BACKGROUND: As the effect of biomedical prevention interventions on the natural history of HIV-1 infection in participants who seroconvert is unknown, the Microbicide Trials Network (MTN) established a longitudinal study (MTN-015) to monitor virologic, immunological, and clinical outcomes, as well as behavioral changes among women who become HIV-infected during MTN trials. We describe the rationale, study design, implementation and enrollment of the initial group of participants in the MTN seroconverter cohort. METHODS: Initiated in 2008, MTN-015 is an ongoing observational cohort study enrolling participants who acquire HIV-1 infection during effectiveness studies of candidate microbicides. Eligible participants from recently completed and ongoing MTN trials are enrolled after seroconversion and return for regular follow-up visits with clinical and behavioral data collection. Biologic samples including blood and genital fluids are stored for future testing. RESULTS: MTN-015 was implemented initially at 6 African sites and enrolled 100/139 (72%) of eligible women who seroconverted in HIV Prevention Trials Network protocol 035 (HPTN 035, conducted by the MTN). The median time from seroconversion in HPTN 035 to enrollment in MTN-015 was 18 months. Retention was good with >70% of visits completed. Implementation challenges included regulatory reviews, translation and testing of questionnaires, and site readiness. CONCLUSIONS: Enrollment of HIV-seroconverters into a longitudinal observational follow up study is feasible and acceptable to participants. Data and samples collected in this protocol will be used to assess safety of investigational HIV microbicides and answer other important public health questions for HIV infected women

Long-term follow-up of HIV seroconverters in microbicide trials – rationale, study design, and challenges in MTN-015

BackgroundAs the effect of biomedical prevention interventions on the natural history of HIV-1 infection in participants who seroconvert is unknown, the Microbicide Trials Network (MTN) established a longitudinal study (MTN-015) to monitor virologic, immunological, and clinical outcomes, as well as behavioral changes among women who become HIV-infected during MTN trials. We describe the rationale, study design, implementation, and enrollment of the initial group of participants in the MTN seroconverter cohort.MethodsInitiated in 2008, MTN-015 is an ongoing observational cohort study enrolling participants who acquire HIV-1 infection during effectiveness studies of candidate microbicides. Eligible participants from recently completed and ongoing MTN trials are enrolled after seroconversion and return for regular follow-up visits with clinical and behavioral data collection. Biologic samples including blood and genital fluids are stored for future testing.ResultsMTN-015 was implemented initially at six African sites and enrolled 100/139 (72%) of eligible women who seroconverted in HIV Prevention Trials Network protocol 035 (HPTN 035, conducted by the MTN). The median time from seroconversion in HPTN 035 to enrollment in MTN-015 was 18 months. Retention was good with >70% of visits completed. Implementation challenges included regulatory reviews, translation, and testing of questionnaires, and site readiness.ConclusionsEnrollment of HIV-seroconverters into a longitudinal observational follow-up study is feasible and acceptable to participants. Data and samples collected in this protocol will be used to assess safety of investigational HIV microbicides and answer other important public health questions for HIV infected women

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

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.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.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.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

Unadjusted Cox proportional hazards model for time to first CD4 ≤ 350 and time to composite disease progression endpoint.

<p>Unadjusted Cox proportional hazards model for time to first CD4 ≤ 350 and time to composite disease progression endpoint.</p

MTN-015 study population of participants from MTN-003 parent protocol.

<p>MTN-015 study population of participants from MTN-003 parent protocol.</p

Linear mixed effects model comparing HIV-1 RNA (log₁₀) and CD4 T-cell counts between the first result 90 days or more after the estimated HIV seroconversion date (intercept) and the 12-month visit (slope) by study arm.

<p>Linear mixed effects model comparing HIV-1 RNA (log₁₀) and CD4 T-cell counts between the first result 90 days or more after the estimated HIV seroconversion date (intercept) and the 12-month visit (slope) by study arm.</p

Participant characteristics¹.

<p>¹Note that the denominators used to calculate percentages throughout this table may vary owing to small amounts of missing data for individual variables and may not sum to 100% due to rounding.</p><p>² Based on a reactive result to the syphilis screening and a positive confirmatory test result. Note that participants testing positive at screening were provided treatment according to WHO guidelines.</p><p>Participant characteristics<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0128857#t002fn001" target="_blank">¹</a>.</p

Summary of subjects screened.

<p>Summary of subjects screened.</p