Prevalence and factors associated with HIV-1 drug resistance mutations in treatment-experienced patients in Nairobi, Kenya: A cross-sectional study.

Abstract

An estimated 1.5 million Kenyans are HIV-seropositive, with 1.1 million on antiretroviral therapy (ART), with the majority of them unaware of their drug resistance status. In this study, we assessed the prevalence of drug resistance to nucleoside reverse transcriptase inhibitors (NRTIs), nucleoside reverse transcriptase inhibitors (NNRTIs), and protease inhibitors, and the variables associated with drug resistance in patients failing treatment in Nairobi, Kenya.This cross-sectional study utilized 128 HIV-positive plasma samples obtained from patients enrolled for routine viral monitoring in Nairobi clinics between 2015 and 2017. The primary outcome was human immunodeficiency virus type 1 (HIV-1) drug resistance mutation counts determined by Sanger sequencing of the polymerase (pol) gene followed by interpretation using Stanford's HIV Drug Resistance Database. Poisson regression was used to determine the effects of sex, viral load, age, HIV-subtype, treatment duration, and ART-regimen on the primary outcome.HIV-1 drug resistance mutations were found in 82.3% of the subjects, with 15.3% of subjects having triple-class ART resistance and 45.2% having dual-class resistance. NRTI primary mutations M184 V/I and K65R/E/N were found in 28.8% and 8.9% of subjects respectively, while NNRTI primary mutations K103N/S, G190A, and Y181C were found in 21.0%, 14.6%, and 10.9% of subjects. We found statistically significant evidence (P = .013) that the association between treatment duration and drug resistance mutations differed by sex. An increase of one natural-log transformed viral load unit was associated with 11% increase in drug resistance mutation counts (incidence rate ratio [IRR] 1.11; 95% CI 1.06–1.16; P < .001) after adjusting for age, HIV-1 subtype, and the sex-treatment duration interaction. Subjects who had been on treatment for 31 to 60 months had 63% higher resistance mutation counts (IRR 1.63; 95% CI 1.12–2.43; P = .013) compared to the reference group (<30 months). Similarly, patients on ART for 61 to 90 months were associated with 133% higher mutation counts than the reference group (IRR 2.33; 95% CI 1.59–3.49; P < .001). HIV-1 subtype, age, or ART-regimen were not associated with resistance mutation counts.Drug resistance mutations were found in alarmingly high numbers, and they were associated with viral load and treatment time. This finding emphasizes the importance of targeted resistance monitoring as a tool for addressing the problem.