Chui Celia, Cheung Peter K, Brumme Chanson J, Mo Theresa, Brumme Zabrina L, Montaner Julio S G, Badley Andrew D, Harrigan P Richard
BC Centre for Excellence in HIV/AIDS, St. Paul's Hospital, Vancouver, British Columbia, Canada.
AIDS Res Hum Retroviruses. 2006 Jul;22(7):615-8. doi: 10.1089/aid.2006.22.615.
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.
VprR77Q与长期非进展性(LTNP)HIV感染有关。我们希望在一组开始高效抗逆转录病毒治疗(HAART)的初治抗逆转录病毒治疗个体中,研究VprR77Q的患病率、临床相关性及其对治疗反应的影响。使用RT-PCR和直接DNA测序对728名受试者的基线血浆样本进行基因分型。采用Cox比例风险回归模型,在中位4.5年的随访期内,模拟VprR77Q对病毒学和免疫学反应以及开始HAART后的生存情况的影响。我们发现,308名受试者(42.3%)单独携带VprR77Q或与另一种氨基酸组合携带,而420名(57.7%)携带的氨基酸不是Q。横断面分析发现,R77Q与基线血浆病毒载量(pVL)、CD4细胞计数、艾滋病诊断或包括年龄、性别和注射吸毒史在内的社会人口学特征之间无相关性(p>0.1)。在多变量分析中,未观察到VprR77Q与HAART初始pVL和CD4反应或治疗开始后的生存之间存在显著关联(p>0.1)。该队列中高患病率以及与治疗前临床参数缺乏相关性,这与R77Q与LTNP状态的关联相悖。这些结果不支持R77Q与HAART反应之间存在关联。