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

• Published in: Journal of medical virology Vol. 87; no. 7; pp. 1149 - 1157
• Main Authors: Seu, Lillian, Mulenga, Lloyd B., Siwingwa, Mpanji, Sikazwe, Izukanji, Lambwe, Nason, Guffey, M. Bradford, Chi, Benjamin H.
• Format: Journal Article
• Language: English
• Published: United States Blackwell Publishing Ltd 01.07.2015; Wiley Subscription Services, Inc
• Subjects: Adult; Anti-HIV Agents - pharmacology; Anti-HIV Agents - therapeutic use; Antiretroviral drugs; Antiretroviral Therapy, Highly Active; diversity; Drug resistance; Drug Resistance, Viral; Female; Genotype; HIV; HIV drug resistance; HIV Infections - drug therapy; HIV Infections - epidemiology; HIV Infections - virology; HIV Protease - genetics; HIV-1 - classification; HIV-1 - drug effects; HIV-1 - genetics; Human immunodeficiency virus; Human immunodeficiency virus 1; Humans; Male; Mutation; NNRTI; Phylogeny; pol; Prevalence; Retrospective Studies; Tertiary Care Centers; Treatment Failure; Viral Load; Virology; Zambia; Zambia - epidemiology; Zambia; NNRTI; diversity; Zambia; pol; HIV drug resistance
• ISSN: 0146-6615; 1096-9071
• DOI: 10.1002/jmv.24162

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. J. Med. Virol. 87:1149–1157, 2015. © 2015 Wiley Periodicals, Inc.