Impact of insertions in the HIV-1 p6 PTAPP region on the virological response to amprenavir.
We evaluated the impact of genetic changes within p6Gag gene on the virological response (VR, mean decrease in plasma viral load at week 12) to unboosted amprenavir (APV). Gag-protease fragments, including gag p2, p7, p1, p6 regions and whole protease (PR) were sequenced from baseline plasma specimens of 84 highly pre-treated but APV-naive patients included in the NARVAL (ANRS 088) trial. The correlation between baseline p6Gag polymorphism, PR mutations, baseline characteristics and VR to APV was analysed in univariate analysis. Insertions (P459Ins) within p6 protein, leading to partial or complete duplication of the PTAPP motif, were significantly associated with a decreased VR (P459Ins versus wild-type; -0.3 +/- 0.8 vs -1.1 +/- 1.2 log copies/ml, P=0.007) and were more frequent when the V82A/F/T/S PR mutation was present (P=0.020). In multivariate analysis, after adjustment on the predictive factors of the VR in the NARVAL trial and on the PR mutations linked with response, there was a strong trend to an association (P=0.058) between the presence of P459Ins and an altered VR. In conclusion, these results suggest that insertions in the p6 region of HIV-1 gag gene may affect the VR, in highly pre-treated patients receiving an unboosted APV-containing regimen.
Lastere
Stephane
S
Laboratoire de Virologie, Hopital Bichat--Claude Bernard, Paris, France. stephane.lastere@bch.ap-hop-paris.fr
Dalban
Cecile
C
Collin
Gilles
G
Descamps
Diane
D
Girard
Pierre-Marie
PM
Clavel
Francois
F
Costagliola
Dominique
D
Brun-Vezinet
Francoise
F
D000328:Adult; D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D002219:Carbamates; D005260:Female; D005663:Furans; D015683:Gene Products, gag / Q000235:genetics*; D005838:Genotype; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology; D017320:HIV Protease Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D015497:HIV-1 / Q000187:drug effects* / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009154:Mutation; D010641:Phenotype; D012367:RNA, Viral / Q000097:blood; D017422:Sequence Analysis, DNA; D013449:Sulfonamides / Q000494:pharmacology / Q000627:therapeutic use*; D019562:Viral Load; D054301:gag Gene Products, Human Immunodeficiency Virus
D002219:Carbamates; D005663:Furans; D015683:Gene Products, gag; D017320:HIV Protease Inhibitors; D012367:RNA, Viral; D013449:Sulfonamides; D054301:gag Gene Products, Human Immunodeficiency Virus; C083002:p6 gag protein, Human immunodeficiency virus 1; C095108:amprenavir