title: Characterization of HIV drug resistance mutations among patients failing first-line antiretroviral therapy from a tertiary referral center in Lusaka, Zambia.
abstract: 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.
authors.affiliation: School of Medicine, University of Alabama at Birmingham, Alabama; Centre for Infectious Disease Research Zambia, Lusaka, Zambia.
authors.forename: Lillian
authors.initials: L
authors.lastname: Seu
authors.forename: Lloyd B
authors.initials: LB
authors.lastname: Mulenga
authors.forename: Mpanji
authors.initials: M
authors.lastname: Siwingwa
authors.forename: Izukanji
authors.initials: I
authors.lastname: Sikazwe
authors.forename: Nason
authors.initials: N
authors.lastname: Lambwe
authors.forename: M Bradford
authors.initials: MB
authors.lastname: Guffey
authors.forename: Benjamin H
authors.initials: BH
authors.lastname: Chi
mesh_terms: D000328:Adult; D019380:Anti-HIV Agents / Q000494:pharmacology* / Q000627:therapeutic use; D023241:Antiretroviral Therapy, Highly Active; D024882:Drug Resistance, Viral; D005260:Female; D005838:Genotype; D015658:HIV Infections / Q000188:drug therapy / Q000453:epidemiology / Q000821:virology*; D016333:HIV Protease / Q000235:genetics; D015497:HIV-1 / Q000145:classification / Q000187:drug effects* / Q000235:genetics*; D006801:Humans; D008297:Male; D009154:Mutation; D010802:Phylogeny; D015995:Prevalence; D012189:Retrospective Studies; D062606:Tertiary Care Centers; D017211:Treatment Failure; D019562:Viral Load; D015024:Zambia / Q000453:epidemiology
chemical_list: D019380:Anti-HIV Agents; D016333:HIV Protease
keywords: HIV drug resistance; NNRTI; Zambia; diversity; pol