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Gag mutations can impact virological response to dual-boosted protease inhibitor combinations in antiretroviral-naïve HIV-infected patients.
- Source :
-
Antimicrobial agents and chemotherapy [Antimicrob Agents Chemother] 2010 Jul; Vol. 54 (7), pp. 2910-9. Date of Electronic Publication: 2010 May 03. - Publication Year :
- 2010
-
Abstract
- ANRS 127 was a randomized pilot trial involving naïve patients receiving two dual-boosted protease inhibitor (PI) combinations. Virological response, defined as a plasma HIV RNA level of <50 copies/ml at week 16, occurred in only 41% patients. Low baseline plasma HIV RNA level was the only significant predictor of virological response. The purpose of this study was to investigate the impact on virological response of pretherapy mutations in cleavage sites of gag, gag-pol, and the gag-pol frameshift region. The whole gag gene and protease-coding region were amplified and sequenced at baseline and at week 16 for 48 patients still on the allocated regimen at week 16. No major PI resistance-associated mutations were detected either at baseline or in the 26 patients who did not achieve virological response at week 16. Baseline cleavage site substitutions in the product of the gag open reading frame at positions 128 (p17/p24) (P = 0.04) and 449 (p1/p6(gag)) (P = 0.01) were significantly more frequent in those patients not achieving virological response. Conversely, baseline cleavage site mutation at position 437 (TFP/p6(pol)) was associated with virological response (P = 0.04). In multivariate analysis adjusted for baseline viral load, these 3 substitutions remained independently associated with virological response. We demonstrated here, in vivo, an impact of baseline polymorphic gag mutations on virological response in naïve patients receiving a combination of two protease inhibitors. However, it was not possible to link the substitutions selected under PI selective pressure with virological failure.
- Subjects :
- Amino Acid Sequence
HIV Protease Inhibitors pharmacology
HIV-1 classification
HIV-1 drug effects
Humans
Molecular Sequence Data
Multivariate Analysis
Phylogeny
Sequence Homology, Amino Acid
HIV Infections drug therapy
HIV Infections genetics
HIV Protease Inhibitors therapeutic use
HIV-1 genetics
Mutation genetics
gag Gene Products, Human Immunodeficiency Virus genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1098-6596
- Volume :
- 54
- Issue :
- 7
- Database :
- MEDLINE
- Journal :
- Antimicrobial agents and chemotherapy
- Publication Type :
- Academic Journal
- Accession number :
- 20439606
- Full Text :
- https://doi.org/10.1128/AAC.00194-10