Human immunodeficiency virus type 1 group m protease in cameroon: genetic diversity and protease inhibitor mutational features.
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.
Fonjungo
Peter N
PN
HIV and Retrovirology Branch, Division of AIDS, STD, and TB Laboratory Research, National Center for Infectious Diseases, Atlanta, Georgia 30333, USA.
Mpoudi
Eitel N
EN
Torimiro
Judith N
JN
Alemnji
George A
GA
Eno
Laura T
LT
Lyonga
Esther J
EJ
Nkengasong
John N
JN
Lal
Renu B
RB
Rayfield
Mark
M
Kalish
Marcia L
ML
Folks
Thomas M
TM
Pieniazek
Danuta
D
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
D004279:DNA, Viral; D017320:HIV Protease Inhibitors; D016333:HIV Protease