Characterization of HIV drug resistance mutations among patients failing first-line antiretroviral therapy from a tertiary referral center in Lusaka, Zambia

In settings of resource constraint, an understanding of HIV drug resistance can guide antiretroviral therapy (ART) at switch to second-line therapy. To determine the prevalence of such HIV drug resistance mutations (HIV DRM), we used an in-house sequencing assay in the pol gene (protease and partial reverse transcriptase) in a cohort of patients suspected of failing a first-line regimen, which in Zambia comprises two nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs) and one non-nucleoside reverse transcriptase inhibitor (NNRTI). Our analysis cohort (n=68) was referred to the University Teaching Hospital in Lusaka from November 2009 to October 2012. Median duration on first-line ART to suspected treatment failure was 3.2 years (IQR 1.7-4.7 years). The majority of patients (95%) harbored HIV-1 subtype C virus. Analysis of reverse transcriptase revealed M184V (88%), K103N/S (32%), and Y181C/I/V (41%) DRMs, with the latter conferring reduced susceptibility to the salvage therapy candidates etravirine and rilpivirine. Three patients (5%) had major protease inhibitor (PI) resistance mutations: all three had the V82A mutation, and one patient (Clade J virus) had a concurrent M46I, Q58E, and L76V DRM. HIV-1 genotyping revealed major and minor DRMs as well as high levels of polymorphisms in subtype C isolates from patients failing first-line antiretroviral therapy. Closer monitoring of DRM mutations at first-line failure can inform clinicians about future options for salvage therapy.