HIV Second-Line Failure and Drug Resistance at High- and Low Level Viremia in Western Ke

Abstract

Objective: Characterize failure and resistance above and below guidelines-recommended 1,000 copies/mL virologic threshold, upon 2nd-line failure. Design: Cross-sectional study. Methods: Kenyan adults on lopinavir/ritonavir-based 2nd-line were enrolled at AMPATH (Academic Model Providing Access to Healthcare). Charts were reviewed for demographic/ clinical characteristics and CD4/viral load (VL) were obtained. Participants with detectable VL had a second visit and pol genotyping was attempted in both visits. Accumulated resistance was defined as mutations in the second, not the first visit. Low level viremia (LLV) was detectable VL<1,000 copies/mL. Failure and resistance associations were evaluated using logistic and Poisson regression, Fisher Exact and t-tests. Results: Of 394 participants (median age 42, 60% female, median 1.9 years on 2nd-line) 48% had detectable VL; 21% had VL>1,000 copies/mL, associated with younger age, tuberculosis treatment, shorter time on 2nd-line, lower CD4 count/percent, longer 1st-line treatment interruption and pregnancy. In 105 sequences from the first visit (35 with LLV), 79% had resistance (57% dual-, 7% triple-class; 46% with intermediate-high-level resistance to ≥1 future drug option). LLV was associated with more overall and NRTI-associated mutations and with predicted resistance to more next-regimen drugs. In 48 second-visit sequences (after median 55 days; IQR 28–33), 40% accumulated resistance and LLV was associated with more mutation accumulation