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Interplay of reverse transcriptase inhibitor therapy and gag p6 diversity in HIV type 1 subtype G and CRF02_AG. AIDS Res Hum Retroviruses 2008 Sep;24(9):1167-74

Date

08/30/2008

Pubmed ID

18729771

Pubmed Central ID

PMC2928033

DOI

10.1089/aid.2007.0308

Scopus ID

2-s2.0-51849135719   6 Citations

Abstract

Abstract The gag p6 region of HIV-1 has various nonsubstitutionary mutations, including insertions, duplications, deletions, and premature stop codons. Studies have linked gag p6 mutations to reduced susceptibility to antiretroviral therapy in HIV-1 subtype B. This study examined the relationship between antiretroviral therapy and gag p6 diversity in HIV-1 CRF02_AG and subtype G. p6 data were generated for secondary analyses following Viroseq genotyping of pol gene sequences in plasma samples from HIV-1-infected Nigerians on reverse transcriptase inhibitor therapy, with virologic failure (repeat VL > 2000 copies/ml). p6 sequence chromatograms were available for 40 CRF02_AG and 43 subtype G-infected individuals. Subjects who had not received their supply of antiretroviral drugs for at least 2 months prior to the plasma sampling were classified as nonadherent. p6 sequences from therapy-adherent individuals had more nonsubstitutionary mutations than sequences from drug-naive individuals (p = 0.0005). The P5L/T mutation was inversely correlated with the presence of K27Q/N in p6, with each mutation being more prominent in subtype G and CRF02_AG, respectively. The data also suggested that P5L/T may be a compensatory mutation for the loss of an essential phosphorylation site in p6. In addition, there was an inverse association between P5L/T mutations in p6 and thymidine analog mutations in reverse transcriptase (p = 0.0001), and drug nonadherence was associated with an 8-fold lower risk of having a nonsubstitutionary mutation in p6 (95% CI = 1.27-52.57). Our data suggest that antiretroviral therapy influences gag p6 diversity, but further studies are needed to clarify these observations.

Author List

Ojesina AI, Chaplin B, Sankalé JL, Murphy R, Idigbe E, Adewole I, Ekong E, Idoko J, Kanki PJ

Author

Akinyemi Ojesina MD, PhD Assistant Professor in the Obstetrics and Gynecology department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Amino Acid Sequence
Amino Acid Substitution
HIV Infections
HIV-1
Humans
Molecular Sequence Data
Mutation, Missense
Nigeria
Polymorphism, Genetic
Reverse Transcriptase Inhibitors
Sequence Alignment
Sequence Analysis, DNA
gag Gene Products, Human Immunodeficiency Virus