title: HIV VprR77Q mutation does not influence clinical response of individuals initiating highly active antiretroviral therapy.
abstract: VprR77Q has been associated with long-term nonprogressive (LTNP) HIV infection. We wished to investigate the prevalence, clinical correlates, and effect on treatment response of VprR77Q in a cohort of antiretroviral- naïve individuals initiating highly active antiretroviral therapy (HAART). Baseline plasma samples from 728 subjects were genotyped using RT-PCR and direct DNA sequencing. Cox proportional hazards regression was used to model the effects of VprR77Q on virologic and immunologic responses, and survival following initiation of HAART, over a median 4.5 years follow-up. We found that 308 subjects (42.3%) harbored VprR77Q alone or in combination with another amino acid, while 420 (57.7%) harbored an amino acid other than Q. A cross-sectional analysis found no correlation between R77Q and baseline plasma viral load (pVL), CD4 count, diagnosis of AIDS, or sociodemographic characteristics including age, gender, and history of injection drug use (p > 0.1). In multivariate analyses, no significant associations between VprR77Q and initial pVL and CD4 responses to HAART or survival following initiation of treatment were observed (p > 0.1). The high prevalence and the lack of association with pretherapy clinical parameters in this cohort argue against an association of R77Q with LTNP status. These results do not support an association between R77Q and HAART response.
authors.affiliation: BC Centre for Excellence in HIV/AIDS, St. Paul's Hospital, Vancouver, British Columbia, Canada.
authors.forename: Celia
authors.initials: C
authors.lastname: Chui
authors.forename: Peter K
authors.initials: PK
authors.lastname: Cheung
authors.forename: Chanson J
authors.initials: CJ
authors.lastname: Brumme
authors.forename: Theresa
authors.initials: T
authors.lastname: Mo
authors.forename: Zabrina L
authors.initials: ZL
authors.lastname: Brumme
authors.forename: Julio S G
authors.initials: JS
authors.lastname: Montaner
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Badley
authors.forename: P Richard
authors.initials: PR
authors.lastname: Harrigan
mesh_terms: D000328:Adult; D000704:Analysis of Variance; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D023241:Antiretroviral Therapy, Highly Active; D001955:British Columbia; D003430:Cross-Sectional Studies; D018450:Disease Progression; D005260:Female; D016334:Genes, vpr / Q000235:genetics*; D015658:HIV Infections / Q000188:drug therapy / Q000235:genetics*; D020276:HIV Long-Term Survivors; D015497:HIV-1 / Q000235:genetics*; D006801:Humans; D008297:Male; D009154:Mutation; D019562:Viral Load
chemical_list: D019380:Anti-HIV Agents