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

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Abstract

Objective:

Characterize failure and resistance above and below guidelines-recommended 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 second-line, 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.

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