Antiretroviral (ARV) choices are challenging in resource-limited settings (RLS) after failure of 2nd-line therapy because of accumulated resistance. Many failing 2nd-line therapy without resistance remain on their 2nd-line therapy. Our objective was to evaluate demographic and predictors of successful virologic suppression in this prospective study.
A5288 was an open-label strategy study in RLS in HIV-1 infected persons with confirmed plasma HIV RNA (VL) ≥ 1000 c/mL after 24 weeks of PI-based 2nd-line ART. The study sought to use newer ARVs (darunavir/r, etravirine and raltegravir) along with genotyping (GT), a cellphone adherence intervention (CPI) or standard of care (SOC), and real-time HIV VL monitoring to achieve VL suppression at week 48. Participants were assigned to 1 of 4 cohorts based on GT at time of study entry, previous ART history and any other GT available. This analysis focuses on the 287 (53%) enrolled in Cohort A (no lopinavir resistance) from Feb-2013 to Dec-2015. These 287 participants remained on 2nd-line PI-based ART regimen, with flexibility to change their NRTIs. Logistic regression was used to evaluate sex, age, baseline HIV-1 RNA, CD4 count, presence of resistance to at least one NRTI, and adherence support (CPI+SOC vs SOC) as predictors of the study’s primary endpoint: suppression of HIV-1 RNA ≤200 c/mL at week 48 (ITT).
56% of Cohort A participants were female, median age was 40. Median HIV-1 RNA was 4.3 log10 c/mL and CD4 count was 171 cells/mm3; 113 (39%) had resistance to at least 1 NRTI and 26 (9%) had minor resistance to at least one PI. 44% of participants achieved VL suppression at week 48. In both unadjusted and adjusted analysis (table), older age, lower baseline HIV-1 RNA, higher CD4 count, and lack of resistance to any NRTI (multivariable only) were significantly associated with higher virologic suppression rate at week 48. Associations with sex and with CPI+SOC were not statistically significant. 145 (51%) experienced confirmed virologic failure ≥ 1000 c/mL and 141 had GT available at failure; 48 (34%) had development of new resistance mutations, predominantly NRTI-related.
In this 3rd-line ART trial in RLS, fewer than 50% of participants with no lopinavir resistance at entry who continued their 2nd-line ART had VL suppression at 48 weeks. Participants with more advanced disease or any resistance mutations had worse rates of suppression. This group likely represents individuals with continued poor ARV adherence.