title: HIV-1 subtype C drug-resistance background among ARV-naive adults in Botswana.
abstract: Current HIV-1 antiretroviral (ARV) drug resistance knowledge is limited to HIV-1 subtype B (HIV-1B). We addressed whether unique genetic and phenotypic properties of HIV-1 subtype C (HIV-1C), southern Africa's most prevalent subtype, may foment earlier and/or distinct resistance mutations. Population-level HIV-1C genotypes were evaluated with respect to drug resistance prevalence before Botswana's public ARV treatment programme began. Viruses were genotyped from 11 representative districts of northern and southern Botswana, and consensus sequences from these 71 individuals and 51 previously reported sequences from HIV-positive blood donors were constructed. Phylogenetic analysis classified all 71 sequences but one, which exhibited pol gene mosaicism, as HIV-1C. The protease and reverse transcriptase coding region had no detectable known primary mutations associated with HIV-1B protease inhibitor (PI) drug resistance. Secondary mutations associated with PI drug resistance were found in all sequences. Several HIV-1C-specific polymorphic sites were found across the pol gene. Northern and southern Botswana viral sequences showed no significant differences from each other. Population genotyping shows that, without countrywide ARV treatment, HIV-1C-infected Batswana harbour virtually no primary mutations known to confer resistance to the three major HIV-1B ARV drug classes. Some secondary PI mutations and polymorphic sites in the protease enzyme necessitate continuous population monitoring, particularly after introduction of countrywide ARV treatment in Botswana. Although its PI resistance development rate and kinetics are not known, our data may suggest increased susceptibility and readiness of HIV-1C to develop resistance under drug pressure when the PI class of drugs is used.
authors.affiliation: Botswana-Harvard School of Public Health AIDS Initiative Partnership, Gaborone, Botswana.
authors.forename: Hermann
authors.initials: H
authors.lastname: Bussmann
authors.forename: Vladimir
authors.initials: V
authors.lastname: Novitsky
authors.forename: William
authors.initials: W
authors.lastname: Wester
authors.forename: Trevor
authors.initials: T
authors.lastname: Peter
authors.forename: Kereng
authors.initials: K
authors.lastname: Masupu
authors.forename: Lesego
authors.initials: L
authors.lastname: Gabaitiri
authors.forename: Soyeon
authors.initials: S
authors.lastname: Kim
authors.forename: Simane
authors.initials: S
authors.lastname: Gaseitsiwe
authors.forename: Thumbi
authors.initials: T
authors.lastname: Ndungú
authors.forename: Richard
authors.initials: R
authors.lastname: Marlink
authors.forename: Ibou
authors.initials: I
authors.lastname: Thior
authors.forename: Max
authors.initials: M
authors.lastname: Essex
mesh_terms: D000595:Amino Acid Sequence; D019380:Anti-HIV Agents / Q000494:pharmacology* / Q000627:therapeutic use*; D001902:Botswana / Q000453:epidemiology; D024882:Drug Resistance, Viral / Q000235:genetics; D005838:Genotype; D015658:HIV Infections / Q000188:drug therapy* / Q000453:epidemiology; D015497:HIV-1 / Q000187:drug effects* / Q000235:genetics; D006801:Humans; D008969:Molecular Sequence Data; D009154:Mutation; D010802:Phylogeny; D011110:Polymorphism, Genetic
chemical_list: D019380:Anti-HIV Agents