Background: Little is known regarding HIV disease outcomes among individuals who become infected with HIV while receiving antiretroviral medications for prevention. We compared HIV disease parameters among women who seroconverted while receiving tenofovir-containing oral or vaginal pre-exposure prophylaxis (PrEP) to placebo.
Methods: Participants with HIV seroconversion in a randomized placebo-controlled trial of oral tenofovir, oral tenofovir/emtricitabine, and vaginal tenofovir gel (MTN-003) were followed in a longitudinal cohort study (MTN-015). The effect of oral and vaginal tenofovir-containing PrEP on HIV disease progression was compared to placebo using linear mixed effects and Cox proportional hazard models, as appropriate. Additional analyses were performed to compare the outcomes among participants with detectable tenofovir or emtricitabine in plasma at the first quarterly visit in MTN-003.
Results: A total of 224 participants were included in the analysis; 93% from South Africa and 94% clade C virus. No differences in HIV RNA at steady state or the trajectory over 12 months were observed for each active arm compared to placebo; tenofovir gel recipients had higher CD4+ T cell counts (722 vs 596 cells/mm3; p = 0.02) at 90 days after estimated HIV seroconversion and higher average rates of change over 12 months compared to placebo (-181 vs -92 cells/mm3 per year; p = 0.08). With a median follow-up of 31 months, no significant differences were observed for time to CD4+ T cell count ≤350 cells/mm3, or the composite endpoint of CD4+ T cells ≤350 cells/mm3, initiation of antiretroviral therapy or death for each active arm compared to placebo. Additionally, there were no significant differences in the HIV RNA or CD4+ T cell counts at baseline, the change to month 12, or any disease progression outcomes among participants with oral drug detected and no oral drug detected compared to placebo.
Conclusions: No clinically significant differences in HIV seroconversion outcomes were observed among women randomized to tenofovir-containing oral or vaginal PrEP regimens, however low overall adherence limits the generalizability of these findings.