HIV-1 second-line failure and drug resistance at high-level and low-level viremia in Western Kenya

Objective: Characterize failure and resistance above and below guidelinesrecommended 1000 copies/ml virologic threshold, upon second-line failure. Design: Cross-sectional study. Methods: Kenyan adults on lopinavir/ritonavir-based second-line were enrolled at AMPATH (Academic Model Providing Access to Healthcare). Charts were reviewed for demographic/clinical characteristics and CD4 /viral load were obtained. Participants with detectable viral load 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 viral load less than 1000 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% women, median 1.9 years on second-line) 48% had detectable viral load; 21% had viral load more than 1000 copies/ ml, associated with younger age, tuberculosis treatment, shorter time on secondline, lower CD4 count/percentage, longer first-line treatment interruption and pregnancy. In 105 sequences from the first visit (35 with LLV), 79% had resistance (57% dual-class, 7% triple-class; 46% with intermediate-To-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. Conclusion: High resistance upon second-line failure exists at levels above and below guideline-recommended virologic-failure threshold, impacting future treatment options. Optimization of care should include increased viral load monitoring, resistance testing and third-line ART access, and consideration of lowering the virologic failure threshold, though this demands further investigation.