title: Accumulation of HIV drug resistance mutations in patients failing first-line antiretroviral treatment in South Africa.
abstract: Patients failing antiretroviral treatment for extended periods of time are at risk of accumulating HIV drug resistance mutations (DRMs), which negatively influences second-line treatment. This retrospective study assessed the rate of DRM accumulation among South African patients with continued virological failure. Serial genotypic resistance testing was performed and DRMs were scored according to the 2009 IAS-USA list. Among 43 patients, 38 (88.4%) harbored ≥1 DRM. The median time between two sequential resistance tests was 5 months (IQR: 3-10). Thymidine analogue mutations accumulated at a rate of 0.07 mutation per month of drug exposure, which is faster than previously reported. Routine virological monitoring should be implemented in resource-limited settings to preserve susceptibility to second-line regimens.
authors.affiliation: PharmAccess Foundation, Amsterdam, The Netherlands. k.sigaloff@pharmaccess.org
authors.forename: Kim C E
authors.initials: KC
authors.lastname: Sigaloff
authors.forename: Tina
authors.initials: T
authors.lastname: Ramatsebe
authors.forename: Raquel
authors.initials: R
authors.lastname: Viana
authors.forename: Tobias F Rinke
authors.initials: TF
authors.lastname: de Wit
authors.forename: Carole L
authors.initials: CL
authors.lastname: Wallis
authors.forename: Wendy S
authors.initials: WS
authors.lastname: Stevens
mesh_terms: D000328:Adult; D019380:Anti-HIV Agents / Q000493:pharmacokinetics*; D024882:Drug Resistance, Viral / Q000187:drug effects / Q000235:genetics*; D005260:Female; D006679:HIV Seropositivity / Q000188:drug therapy* / Q000453:epidemiology / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009154:Mutation; D012367:RNA, Viral / Q000187:drug effects*; D012189:Retrospective Studies; D013019:South Africa / Q000453:epidemiology; D013936:Thymidine / Q000031:analogs & derivatives / Q000493:pharmacokinetics*; D017211:Treatment Failure; D019562:Viral Load / Q000187:drug effects
chemical_list: D019380:Anti-HIV Agents; D012367:RNA, Viral; D013936:Thymidine