title: Low-abundance resistant mutations in HIV-1 subtype C antiretroviral therapy-naive individuals as revealed by pyrosequencing.
abstract: Given the recent scale-up of antiretroviral therapy (ART) in sub-Saharan Africa, we sought to determine how often and at what levels do drug-resistant mutant variants exist in ART-naive HIV subtype C infected individuals. Samples from 10 ART-naive Zambian individuals were subjected to ultra-deep pyrosequencing (UDPS) to characterize the frequency of low-abundance drug resistance mutations in the pol gene. Low-abundance clinically relevant variants were detected for nucleoside reverse transcriptase inhibitors (NRTIs), non-nucleoside reverse transcriptase inhibitors (NNRTIs) and protease inhibitors (PIs) in eight of the ten subjects. Intermediate to high-level resistance was predicted for the majority of NRTIs. Mutations conferring resistance to most first-line and some second-line therapy drugs were also observed. UDPS detected a number of additional major resistant mutations suggesting that these individuals may have an increased risk of virological failure after initiating ART. Moreover, the effectiveness of first-line and even some secondline ART may be compromised in this setting.
authors.affiliation: Nebraska Center for Virology, Morrison Center, University of Nebraska-Lincoln, 4240 Fair St, Lincoln, NE 68583-0900, USA.
authors.forename: Sandra
authors.initials: S
authors.lastname: Gonzalez
authors.affiliation: Nebraska Center for Virology, Morrison Center, University of Nebraska-Lincoln, 4240 Fair St, Lincoln, NE 68583-0900, USA.
authors.forename: Damien C
authors.initials: DC
authors.lastname: Tully
authors.affiliation: Nebraska Center for Virology, Morrison Center, University of Nebraska-Lincoln, 4240 Fair St, Lincoln, NE 68583-0900, USA.|Virology Department, University Teaching Hospital, P.O. Box 50223, Lusaka, 10101, Zambia.
authors.forename: Clement
authors.initials: C
authors.lastname: Gondwe
authors.affiliation: Nebraska Center for Virology, Morrison Center, University of Nebraska-Lincoln, 4240 Fair St, Lincoln, NE 68583-0900, USA.
authors.forename: Charles
authors.initials: C
authors.lastname: Wood
mesh_terms: D000328:Adult; D019380:Anti-HIV Agents / Q000494:pharmacology; D024882:Drug Resistance, Viral / Q000235:genetics*; D005260:Female; D005838:Genotype; D015658:HIV Infections / Q000821:virology*; D054303:HIV Reverse Transcriptase / Q000037:antagonists & inhibitors* / Q000235:genetics; D015497:HIV-1 / Q000187:drug effects / Q000235:genetics*; D006801:Humans; D008297:Male; D009154:Mutation; D011480:Protease Inhibitors / Q000494:pharmacology; D018894:Reverse Transcriptase Inhibitors / Q000494:pharmacology; D017422:Sequence Analysis, DNA / Q000379:methods; D015024:Zambia
chemical_list: D019380:Anti-HIV Agents; D011480:Protease Inhibitors; D018894:Reverse Transcriptase Inhibitors; D054303:HIV Reverse Transcriptase