RESUMEN
OBJECTIVE: Characterize failure and resistance above and below guidelines-recommended 1000âcopies/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 1000âcopies/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 1000âcopies/ml, associated with younger age, tuberculosis treatment, shorter time on second-line, lower CD4count/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.
Asunto(s)
Fármacos Anti-VIH/farmacología , Fármacos Anti-VIH/uso terapéutico , Farmacorresistencia Viral , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/virología , Adulto , Recuento de Linfocito CD4 , Estudios Transversales , Femenino , Genotipo , VIH-1/efectos de los fármacos , VIH-1/genética , VIH-1/aislamiento & purificación , Humanos , Kenia , Lopinavir/farmacología , Lopinavir/uso terapéutico , Masculino , Persona de Mediana Edad , Ritonavir/farmacología , Ritonavir/uso terapéutico , Análisis de Secuencia de ADN , Insuficiencia del Tratamiento , Carga Viral , Viremia/tratamiento farmacológico , Viremia/virología , Productos del Gen pol del Virus de la Inmunodeficiencia Humana/genéticaRESUMEN
BACKGROUND: Antiretroviral treatment interruptions (TIs) cause suboptimal clinical outcomes. Data on TIs during social disruption are limited. METHODS: We determined effects of unplanned TIs after the 2007-2008 Kenyan postelection violence on virological failure, comparing viral load (VL) outcomes in HIV-infected adults with and without conflict-induced TI. RESULTS: Two hundred and one patients were enrolled, median 2.2 years after conflict and 4.3 years on treatment. Eighty-eight patients experienced conflict-related TIs and 113 received continuous treatment. After adjusting for preconflict CD4, patients with TIs were more likely to have detectable VL, VL >5,000 and VL >10,000. CONCLUSIONS: Unplanned conflict-related TIs are associated with increased likelihood of virological failure.