title: High prevalence of antiretroviral resistance in treated Ugandans infected with non-subtype B human immunodeficiency virus type 1.
abstract: This study examined the emergence and prevalence of drug-resistant mutations in reverse transcriptase and protease coding regions in human immunodeficiency virus type 1 (HIV-1)-infected Ugandans treated with antiretroviral drugs (ARV). Genotypic resistance testing was performed on 50 and 16 participants who were enrolled in a cross-sectional and longitudinal observational cohort, respectively. The majority of the 113 HIV-1 PR-RT sequences were classified as subtypes A and D. Drug resistance mutations were prevalent in 52% of ARV-experienced individuals, and 17 of 27 ARV-resistant isolates had three mutations or more in reverse transcriptase. Resistance mutations in protease were less prevalent but only 17 of the 50 patients were receiving a protease inhibitor upon sample collection. Mutations conferring drug resistance were also selected in 3 of 16 participants in the longitudinal cohort, i.e., less than 8 months after the initiation of ARV treatment. Rapid emergence of ARV resistance was associated with poor adherence to treatment regimens, which was related to treatment costs. ARV resistance did, however, appear at a slightly higher prevalence in HIV-1 subtype D (21 of 33) than subtype A (7 of 25) infected individuals. Overall, this observational study suggests that ARV-resistant HIV-1 isolates are emerging rapidly in ARV-treated individual in Uganda and possibly other developing countries.
authors.affiliation: Division of Infectious Diseases, Department of Medicine, Case Western Reserve University, Cleveland, Ohio 44106, USA. eja3@po.cwru.edu
authors.forename: Nathalie
authors.initials: N
authors.lastname: Richard
authors.forename: Marisa
authors.initials: M
authors.lastname: Juntilla
authors.forename: Awet
authors.initials: A
authors.lastname: Abraha
authors.forename: Korey
authors.initials: K
authors.lastname: Demers
authors.forename: Ellen
authors.initials: E
authors.lastname: Paxinos
authors.forename: Justin
authors.initials: J
authors.lastname: Galovich
authors.forename: Christo
authors.initials: C
authors.lastname: Petropoulos
authors.forename: Christopher C
authors.initials: CC
authors.lastname: Whalen
authors.forename: Fred
authors.initials: F
authors.lastname: Kyeyune
authors.forename: Diana
authors.initials: D
authors.lastname: Atwine
authors.forename: Cissy
authors.initials: C
authors.lastname: Kityo
authors.forename: Peter
authors.initials: P
authors.lastname: Mugyenyi
authors.forename: Eric J
authors.initials: EJ
authors.lastname: Arts
mesh_terms: D000328:Adult; D019380:Anti-HIV Agents / Q000494:pharmacology* / Q000627:therapeutic use; D003430:Cross-Sectional Studies; D004279:DNA, Viral / Q000737:chemistry / Q000302:isolation & purification; D024882:Drug Resistance, Viral / Q000235:genetics*; D005260:Female; D005838:Genotype; D015658:HIV Infections / Q000188:drug therapy / Q000821:virology*; D016333:HIV Protease / Q000235:genetics; D054303:HIV Reverse Transcriptase / Q000235:genetics; D015497:HIV-1 / Q000145:classification / Q000187:drug effects* / Q000235:genetics* / Q000302:isolation & purification; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D020125:Mutation, Missense; D010802:Phylogeny; D011533:Proviruses / Q000235:genetics / Q000302:isolation & purification; D012307:Risk Factors; D016312:Treatment Refusal; D014454:Uganda; D014766:Viremia
chemical_list: D019380:Anti-HIV Agents; D004279:DNA, Viral; D054303:HIV Reverse Transcriptase; D016333:HIV Protease