title: Prevalence of drug resistance-related polymorphisms in treatment-naive individuals infected with nonsubtype B HIV type 1 in Cameroon.
abstract: Mutations associated with the use of protease (PR) and reverse transcriptase (RT) inhibitors have been mostly mapped for HIV-1 subtype B. The prevalence of these mutations in drug-naive HIV-1 subtype B-infected individuals is low but occurs at high frequencies in treated individuals. To determine the prevalence of treatment-associated mutations in non-B viruses, we analyzed a 1613-bp pol region of specimens collected from 57 HIV-1-infected treatment-naive individuals from Cameroon. Of the 57 HIV-1 sequences, 43 belonged to CRF02-AG, two to CRF11-cpx, six to subtype A, one to subtype D, and five were unclassifiable. Of the 57 PR sequences, 100% contained at least one codon change giving substitutions at positions 10, 11, 16, 20, 33, 36, 60, 62, 64, 69, 77, and 89. These substitutions gave the following prevalence pattern, 36I/L (100%, 57/57) >89M/I (98%, 56/57)>69K/R (93%, 53/57)>20I/R (89%, 51/57)>16E (16%, 9/57)>64M (12%, 7/57)>10I (11%, 6/57)>11V (5%, 3/57)=62V (5%, 3/57)=77I (5%, 3/57)>233F/V (4%, 2/57)=60E (4%), which differed significantly from subtype B at positions 20, 36, 69, and 89. All but one (98%) of the 57 RT sequences (438 amino acid residues) carried substitutions located at codons 39A (7%), 43E (7%), 122E (7%), 312Q (2%), 333E (2%), 335C/D (89%), 356K (89%), 358K (14%), 365I (2%), 371V (81%), 376S (11%), or 399D (4%); the frequency of these substitutions ranged from <0.5% to 4% in RT of subtype B. The high prevalence of minor mutations associated with protease inhibitors (PI) and reverse transcriptase inhibitors (RTI) represents natural polymorphisms. HIV-1 PR and RT sequences from antiretroviral (ARV)-naive HIV-infected persons in Cameroon are important for monitoring the development of resistance to PIs and RTIs as such mutations could lead to treatment failures in individuals undergoing ARV therapy.
authors.affiliation: Laboratory Branch, Division of HIV/AIDS Prevention, National Center for HIV, Hepatitis, STD, and TB Prevention (NCHHSTP), Centers for Disease Control and Prevention, Atlanta, Georgia, USA.
authors.forename: Ae S
authors.initials: AS
authors.lastname: Youngpairoj
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: Mbia A
authors.initials: MA
authors.lastname: Eloundou
authors.forename: Vedapuri
authors.initials: V
authors.lastname: Shanmugam
authors.forename: Eitel N
authors.initials: EN
authors.lastname: Mpoudi
authors.forename: Thomas M
authors.initials: TM
authors.lastname: Folks
authors.forename: Marcia L
authors.initials: ML
authors.lastname: Kalish
authors.forename: Danuta
authors.initials: D
authors.lastname: Pieniazek
authors.forename: Peter N
authors.initials: PN
authors.lastname: Fonjungo
mesh_terms: D000328:Adult; D000595:Amino Acid Sequence; D002163:Cameroon / Q000453:epidemiology; D004279:DNA, Viral / Q000235:genetics; D024882:Drug Resistance, Viral / Q000235:genetics*; D005260:Female; D016333:HIV Protease / Q000235:genetics*; D017320:HIV Protease Inhibitors / Q000494:pharmacology*; D006679:HIV Seropositivity / Q000453:epidemiology* / Q000235:genetics*; D015497:HIV-1 / Q000235:genetics*; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation; D010802:Phylogeny; D011110:Polymorphism, Genetic; D015995:Prevalence; D018894:Reverse Transcriptase Inhibitors / Q000494:pharmacology*
chemical_list: D004279:DNA, Viral; D017320:HIV Protease Inhibitors; D018894:Reverse Transcriptase Inhibitors; D016333:HIV Protease; C514803:p16 protease, Human immunodeficiency virus 1