title: Antiretroviral drug susceptibility among HIV-infected adults failing antiretroviral therapy in Rakai, Uganda.
abstract: We analyzed antiretroviral drug susceptibility in HIV-infected adults failing first- and second-line antiretroviral treatment (ART) in Rakai, Uganda. Samples obtained from participants at baseline (pretreatment) and at the time of failure on first-line ART and second-line ART were analyzed using genotypic and phenotypic assays for antiretroviral drug resistance. Test results were obtained from 73 samples from 38 individuals (31 baseline samples, 36 first-line failure samples, and six second-line failure samples). Four (13%) of the 31 baseline samples had mutations associated with resistance to nucleoside or nonnucleoside reverse transcriptase inhibitors (NRTIs and NNRTIs, respectively). Among the 36 first-line failure samples, 31 (86%) had NNRTI resistance mutations and 29 (81%) had lamivudine resistance mutations; only eight (22%) had other NRTI resistance mutations. None of the six individuals failing a second-line protease inhibitor (PI)-based regimen had PI resistance mutations. Six (16%) of the participants had discordant genotypic and phenotypic test results. Genotypic resistance to drugs included in first-line ART regimens was detected prior to treatment and among participants failing first-line ART. PI resistance was not detected in individuals failing second-line ART. Surveillance for transmitted and acquired drug resistance remains a priority for scale-up of ART.
authors.affiliation: Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA. sjr@jhmi.edu
authors.forename: Steven J
authors.initials: SJ
authors.lastname: Reynolds
authors.forename: Oliver
authors.initials: O
authors.lastname: Laeyendecker
authors.forename: Gertrude
authors.initials: G
authors.lastname: Nakigozi
authors.forename: Joel E
authors.initials: JE
authors.lastname: Gallant
authors.forename: Wei
authors.initials: W
authors.lastname: Huang
authors.forename: Sarah E
authors.initials: SE
authors.lastname: Hudelson
authors.forename: Thomas C
authors.initials: TC
authors.lastname: Quinn
authors.forename: Kevin
authors.initials: K
authors.lastname: Newell
authors.forename: David
authors.initials: D
authors.lastname: Serwadda
authors.forename: Ronald H
authors.initials: RH
authors.lastname: Gray
authors.forename: Maria J
authors.initials: MJ
authors.lastname: Wawer
authors.forename: Susan H
authors.initials: SH
authors.lastname: Eshleman
mesh_terms: D000293:Adolescent; D000328:Adult; D044966:Anti-Retroviral Agents / Q000008:administration & dosage*; D023241:Antiretroviral Therapy, Highly Active / Q000379:methods*; D024882:Drug Resistance, Viral; D005260:Female; D005838:Genotype; D006678:HIV / Q000187:drug effects* / Q000235:genetics* / Q000302:isolation & purification; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology*; D016333:HIV Protease / Q000235:genetics; D054303:HIV Reverse Transcriptase / Q000235:genetics; D006801:Humans; D008297:Male; D008826:Microbial Sensitivity Tests; D008969:Molecular Sequence Data; D020125:Mutation, Missense; D017422:Sequence Analysis, DNA; D017211:Treatment Failure; D014454:Uganda; D055815:Young Adult
chemical_list: D044966:Anti-Retroviral Agents; D054303:HIV Reverse Transcriptase; D016333:HIV Protease