OBJECTIVE: To identify novel viral determinants in HIV-1 protease, Gag, and envelope V3 that relate to outcomes to initial protease inhibitor-based antiretroviral therapy. DESIGN: A longitudinal cohort study of protease inhibitor-naive, HIV-infected individuals was designed to identify genetic variables in viral Gag and envelope sequences associated with response to antiretroviral therapy. METHODS: Genetic and statistical models, including amino acid profiles, phylogenetic analyses, receiver operating characteristic analyses, and covariation analyses, were used to evaluate viral sequences and clinical variables from individuals who developed immune reconstitution with or without suppression of viral replication. RESULTS: Pretherapy chemokine (C-X-C motif) receptor 4-using V3 regions had significant associations with viral failure (P = 0.04). Amino acid residues in protease covaried with Gag residues, particularly in p7(NC), independent of cleavage sites. Pretherapy V3 charge combined with p6(Pol) and p2/p7(NC) cleavage site genotypes produced the best three-variable model to predict viral suppression in 88% of individuals. Combinations of baseline CD4 cell percentage with genetic determinants in Gag-protease predicted viral fitness in 100% of individuals who failed to suppress viral replication. CONCLUSION: Baseline genetic determinants in Gag p6(Pol) and p2/p7(NC), as well as envelope, provide novel combinations of biomarkers for predicting emergence of viral resistance to initial therapy regimens.
OBJECTIVE: To identify novel viral determinants in HIV-1 protease, Gag, and envelope V3 that relate to outcomes to initial protease inhibitor-based antiretroviral therapy. DESIGN: A longitudinal cohort study of protease inhibitor-naive, HIV-infected individuals was designed to identify genetic variables in viral Gag and envelope sequences associated with response to antiretroviral therapy. METHODS: Genetic and statistical models, including amino acid profiles, phylogenetic analyses, receiver operating characteristic analyses, and covariation analyses, were used to evaluate viral sequences and clinical variables from individuals who developed immune reconstitution with or without suppression of viral replication. RESULTS: Pretherapy chemokine (C-X-C motif) receptor 4-using V3 regions had significant associations with viral failure (P = 0.04). Amino acid residues in protease covaried with Gag residues, particularly in p7(NC), independent of cleavage sites. Pretherapy V3 charge combined with p6(Pol) and p2/p7(NC) cleavage site genotypes produced the best three-variable model to predict viral suppression in 88% of individuals. Combinations of baseline CD4 cell percentage with genetic determinants in Gag-protease predicted viral fitness in 100% of individuals who failed to suppress viral replication. CONCLUSION: Baseline genetic determinants in Gag p6(Pol) and p2/p7(NC), as well as envelope, provide novel combinations of biomarkers for predicting emergence of viral resistance to initial therapy regimens.
Authors: S M Essajee; M Kim; C Gonzalez; M Rigaud; A Kaul; S Chandwani; W Hoover; R Lawrence; H Spiegel; H Pollack; K Krasinski; W Borkowsky Journal: AIDS Date: 1999-12-24 Impact factor: 4.177
Authors: Roxana M Coman; Arthur H Robbins; Marty A Fernandez; C Taylor Gilliland; Anthony A Sochet; Maureen M Goodenow; Robert McKenna; Ben M Dunn Journal: Biochemistry Date: 2007-12-20 Impact factor: 3.162
Authors: N Yahi; C Tamalet; C Tourrès; N Tivoli; F Ariasi; F Volot; J A Gastaut; H Gallais; J Moreau; J Fantini Journal: J Clin Microbiol Date: 1999-12 Impact factor: 5.948
Authors: Guity Ghaffari; Dominick J Passalacqua; Jennifer L Caicedo; Maureen M Goodenow; John W Sleasman Journal: Pediatrics Date: 2004-10-18 Impact factor: 7.124
Authors: E E Perez; S L Rose; B Peyser; S L Lamers; B Burkhardt; B M Dunn; A D Hutson; J W Sleasman; M M Goodenow Journal: J Infect Dis Date: 2001-01-19 Impact factor: 5.226
Authors: Mark A Wallet; Carina A Rodriguez; Li Yin; Sara Saporta; Sasawan Chinratanapisit; Wei Hou; John W Sleasman; Maureen M Goodenow Journal: AIDS Date: 2010-06-01 Impact factor: 4.177
Authors: Mark A Wallet; Caroline M Reist; Julie C Williams; Sofia Appelberg; Giorgio L Guiulfo; Brent Gardner; John W Sleasman; Maureen M Goodenow Journal: J Leukoc Biol Date: 2012-07-11 Impact factor: 4.962
Authors: Li Yin; Li Liu; Yijun Sun; Wei Hou; Amanda C Lowe; Brent P Gardner; Marco Salemi; Wilton B Williams; William G Farmerie; John W Sleasman; Maureen M Goodenow Journal: Retrovirology Date: 2012-12-17 Impact factor: 4.602
Authors: Mattia C F Prosperi; Li Yin; David J Nolan; Amanda D Lowe; Maureen M Goodenow; Marco Salemi Journal: Sci Rep Date: 2013-10-03 Impact factor: 4.379