Abstract and Introduction
Background: Sex differences in studies of antiretroviral (ART) drug exposure and treatment outcomes support the hypothesis that some ART combinations may not be well tolerated in women. We evaluated disparities in outcomes between men and women participating in ACTG A5288, an interventional strategy trial for individuals failing a protease inhibitor–based second-line ART regimen in low- and middle-income countries.
Methods: Participants were assigned to one of 4 cohorts (A-D) based on resistance profiles and ART history. Cohort A had no lopinavir/ritonavir (LPV/r) resistance and stayed on their second-line regimen, and cohorts B, C, and D had increasing resistance and accessed novel ART regimens. In this secondary analysis, we evaluated sex differences in the primary endpoint, HIV-1 RNA ≤200 copies/mL at week 48; confirmed virologic failure ≥1000 copies/mL (VF); and clinical outcomes and adverse events (intent-to-treat).
Results: Women made up 258/545 (47%) of the study population. More women than men were assigned to cohort A. Median follow-up was 72 weeks. Fewer women than men had HIV-1 RNA ≤200 copies/mL at week 48: 39% vs. 49% in cohort A and 83% vs. 89% in cohorts B, C, and D combined. More women experienced VF, grade ≥3 signs and symptoms, but similar grade ≥3 diagnoses or laboratory abnormalities.
Conclusions: More women than men entered the study with a resistance profile suggesting that their second-line regimen could have been effective in maintaining virologic suppression. The more frequent occurrence of grade ≥3 signs and symptoms in women suggests that tolerability issues were under recognized in women on protease inhibitor–based therapy.
Antiretroviral treatment (ART) options for people living with HIV (PLH) are constrained in low- and middle-income countries (LMIC), and fewer drugs are available to individuals experiencing treatment failure. Typically, there is one recommended first-line regimen, either a non-NRTI (NNRTI)-based regimen, or more recently a dolutegravir (DTG)-based regimen, with 2 NRTIs. Second-line regimens have used a boosted protease inhibitor (PI), either lopinavir/ritonavir or atazanavir/ritonavir, with modifications of the other components of the regimen. Modifications can be made but are dependent on availability of the desired drugs or drug combinations. Third-line regimens may be unavailable or difficult to access, sometimes requiring application to central authorities such as ministries of health. Given these circumstances, identifying and addressing barriers to adherence allows for targeted interventions that may enhance treatment success.
A5288 was an open-label phase IV, prospective interventional strategy study at 19 urban sites in 10 LMIC in Africa (Kenya, Malawi, South Africa, Uganda, and Zimbabwe), Latin America (Brazil, Haiti, and Peru), and Asia (India and Thailand) evaluating treatment options for individuals experiencing confirmed virological failure (VF) on their PI-based second-line regimen. We report here results from a secondary analysis of differences in outcomes by sex in this diverse study population.
J Acquir Immune Defic Syndr. 2020;84(2):203-207. © 2020 Lippincott Williams & Wilkins