Interplay of reverse transcriptase inhibitor therapy and gag p6 diversity in HIV type 1 subtype G and CRF02_AG.
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.
Ojesina
Akinyemi I
AI
Harvard School of Public Health, Department of Immunology and Infectious Diseases, Boston, Massachusetts 02115, USA.
Chaplin
Beth
B
Sankalé
Jean-Louis
JL
Murphy
Robert
R
Idigbe
Emmanuel
E
Adewole
Isaac
I
Ekong
Ernest
E
Idoko
John
J
Kanki
Phyllis J
PJ
D000595:Amino Acid Sequence; D019943:Amino Acid Substitution / Q000235:genetics; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology*; D015497:HIV-1 / Q000145:classification* / Q000187:drug effects* / Q000235:genetics; D006801:Humans; D008969:Molecular Sequence Data; D020125:Mutation, Missense; D009549:Nigeria; D011110:Polymorphism, Genetic; D018894:Reverse Transcriptase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D016415:Sequence Alignment; D017422:Sequence Analysis, DNA; D054301:gag Gene Products, Human Immunodeficiency Virus / Q000235:genetics*
D018894:Reverse Transcriptase Inhibitors; D054301:gag Gene Products, Human Immunodeficiency Virus; C083002:p6 gag protein, Human immunodeficiency virus 1