title: Human immunodeficiency virus type 1 group m protease in cameroon: genetic diversity and protease inhibitor mutational features.
abstract: To establish a baseline for monitoring resistance to protease inhibitors (PIs) and examining the efficacy of their use among persons in Cameroon infected with human immunodeficiency virus type 1 (HIV-1), we analyzed genetic variability and PI resistance-associated substitutions in PCR-amplified protease (PR) sequences in strains isolated from 110 HIV-1-infected, drug-naïve Cameroonians. Of the 110 strains, 85 were classified into six HIV-1 PR subtypes, A (n = 1), B (n = 1), F (n = 4), G (n = 7), H (n = 1), and J (n = 7), and a circulating recombinant form, CRF02-AG (n = 64). PR genes from the remaining 25 (23%) specimens were unclassifiable, whereas 2% (7 of 301) unclassifiable PR sequences were reported for a global collection. Two major PI resistance-associated mutations, 20M and 24I, were detected in strains from only two specimens, whereas secondary mutations were found in strains from all samples except one strain of subtype B and two strains of CRF02-AG. The secondary mutations showed the typical PI resistance-associated pattern for non-subtype B viruses in both classifiable and unclassifiable PR genes, with 36I being the predominant (99%) mutation, followed by 63P (18%), 20R (15%), 77I (13%), and 10I or 10V (11%). Of these mutations, dual and triple PI resistance-associated substitutions were found in 38% of all the Cameroonian strains. Compared with classifiable PR sequences, unclassifiable sequences had significantly more dual and triple substitutions (64% versus 30%; P = 0.004). Phenotypic and clinical evaluations are needed to estimate whether PI resistance during antiretroviral drug treatment occurs more rapidly in individuals infected with HIV-1 strains harboring multiple PI resistance-associated substitutions. This information may be important for determination of appropriate drug therapies for HIV-1-infected persons in Cameroon, where more than one-third of HIV-1 strains were found to carry dual and triple minor PI resistance-associated mutations.
authors.affiliation: HIV and Retrovirology Branch, Division of AIDS, STD, and TB Laboratory Research, National Center for Infectious Diseases, Atlanta, Georgia 30333, USA.
authors.forename: Peter N
authors.initials: PN
authors.lastname: Fonjungo
authors.forename: Eitel N
authors.initials: EN
authors.lastname: Mpoudi
authors.forename: Judith N
authors.initials: JN
authors.lastname: Torimiro
authors.forename: George A
authors.initials: GA
authors.lastname: Alemnji
authors.forename: Laura T
authors.initials: LT
authors.lastname: Eno
authors.forename: Esther J
authors.initials: EJ
authors.lastname: Lyonga
authors.forename: John N
authors.initials: JN
authors.lastname: Nkengasong
authors.forename: Renu B
authors.initials: RB
authors.lastname: Lal
authors.forename: Mark
authors.initials: M
authors.lastname: Rayfield
authors.forename: Marcia L
authors.initials: ML
authors.lastname: Kalish
authors.forename: Thomas M
authors.initials: TM
authors.lastname: Folks
authors.forename: Danuta
authors.initials: D
authors.lastname: Pieniazek
mesh_terms: D000595:Amino Acid Sequence; D004279:DNA, Viral / Q000737:chemistry; D024882:Drug Resistance, Viral; D014644:Genetic Variation; D016333:HIV Protease / Q000737:chemistry / Q000235:genetics*; D017320:HIV Protease Inhibitors / Q000494:pharmacology*; D015497:HIV-1 / Q000187:drug effects*; D006801:Humans; D008969:Molecular Sequence Data; D009154:Mutation; D010802:Phylogeny
chemical_list: D004279:DNA, Viral; D017320:HIV Protease Inhibitors; D016333:HIV Protease