Fontdevila Maria Casadellà, Cozzi-Lepri Alessandro, Phillips Andrew, Julian Marc Noguera, Bickel Marcus, Sedlacek Dalibor, Kronborg Gitte, Lazzarin Adriano, Zilmer Kai, Clotet Bonaventura, Lundgren Jens D, Paredes Roger
IrsiCaixa AIDS Research Institute, Barcelona, Spain.
Royal Free Hospital, London, UK.
J Int AIDS Soc. 2014 Nov 2;17(4 Suppl 3):19685. doi: 10.7448/IAS.17.4.19685. eCollection 2014.
It is uncertain if plasma HIV-1 tropism is an independent predictor of short-term risk of clinical progression / death, in addition to the CD4 count and HIV RNA level. We conducted a nested case-control study within EuroSIDA to assess this question amongst people with current HIV RNA level >1000 copies/mL, including both people on ART and those ART naïve.
People with an AIDS diagnosis or who died from any causes for whom there was a stored plasma sample with HIV-1 RNA (VL)≥1,000 copies/mL available in the time window of 3-12 months prior to the event were identified. At least one control was selected for each case matched for age, VL and HCV status at the time of sampling. Controls were event-free after a matched duration of time from the date of sampling. Plasma HIV tropism was estimated using 454 and population sequencing (PS). Non-R5 HIV was defined as: (a) ≥2% of sequences with a Geno2Pheno (G2P) FPR≤3.75% by 454, and (b) a G2P FPR≤10% by PS. We also compared CD4 slopes over the 12 months following the date of sampling using a linear mixed model with random intercept according to HIV tropism and ART status.
The study included 266 subjects, 100 cases and 166 controls, with sample taken on average in 2006; 23% and 24% had non-R5 HIV by 454 and PS respectively. There were 19% women, 25% MSM, 92% Caucasians, 22% HCV+. At the time of sampling, 26% were ART-naïve, 25% had started but were off ART and 49% were receiving ART. The median age, CD4 and viral load was 41 years, 350 cells/mm(3) and 4.81 log c/mL, respectively. Baseline characteristics were well balanced by tropism. Factors independently associated with clinical progression or death were female gender (OR=2.12; 95% CI=1.04, 4.36; p=0.038), CD4+ count (OR=0.90 per 100 cells/mm(3) higher; 95% CI 0.80, 1.00; p=0.058), being on ART (OR=2.72; 95% CI 1.15, 6.41; p=0.022) and calendar year of sample (OR=0.84 per more recent year; 95% CI=0.77, 0.91; p<0.001). Baseline plasma tropism was not an independent risk factor for clinical progression or death by either 454 or PS. No significant interaction was observed between tropism and ART status. There were no significant differences in the CD4+ slope within or between tropism groups.
Plasma HIV-1 tropism does not appear to add to the ability of CD4 count and viral load to predict the short term risk of AIDS and death outcomes, even with 454 sequencing.
除了CD4细胞计数和HIV RNA水平外，血浆HIV-1嗜性是否是临床进展/死亡短期风险的独立预测因素尚不确定。我们在欧洲艾滋病临床与流行病学研究（EuroSIDA）中开展了一项巢式病例对照研究，以评估当前HIV RNA水平>1000拷贝/mL的人群中的这一问题，包括接受抗逆转录病毒治疗（ART）的人群和未接受ART的人群。
确定那些在事件发生前3至12个月时间窗内有HIV-1 RNA（病毒载量，VL）≥1000拷贝/mL的储存血浆样本、被诊断为艾滋病或因任何原因死亡的患者。为每个病例至少选择一名对照，对照在采样时按年龄、VL和丙型肝炎病毒（HCV）状态进行匹配。从采样日期起经过匹配的时间段后，对照无事件发生。使用454测序和群体测序（PS）估计血浆HIV嗜性。非R5 HIV定义为：（a）454测序中≥2%的序列其基因2表型（G2P）假阳性率（FPR）≤3.75%，以及（b）PS测序中G2P FPR≤10%。我们还使用具有随机截距的线性混合模型，根据HIV嗜性和ART状态比较采样日期后12个月内的CD4细胞斜率。
该研究纳入了266名受试者，100例病例和166名对照，样本平均采集于2006年；分别有23%和24%的受试者通过454测序和PS测序检测到非R5 HIV。女性占19%，男男性行为者占25%，白种人占92%，HCV阳性者占22%。在采样时，26%的受试者未接受ART，25%的受试者已开始但停用了ART，49%的受试者正在接受ART。中位年龄、CD细胞计数和病毒载量分别为41岁、350个细胞/mm³和4.81 log₁₀拷贝/mL。基线特征在嗜性组间均衡良好。与临床进展或死亡独立相关的因素为女性性别（比值比[OR]=2.12；95%置信区间[CI]=1.04, 4.36；p=0.038）、CD4⁺细胞计数（每高100个细胞/mm³，OR=0.90；95% CI 0.80, 1.00；p=0.058）、接受ART治疗（OR=2.72；95% CI 1.15, 6.41；p=0.022）以及样本采集的日历年（每更近一年，OR=0.84；95% CI=0.77, 0.91；p<0.001）。通过454测序或PS测序，基线血浆嗜性均不是临床进展或死亡的独立危险因素。在嗜性与ART状态之间未观察到显著的相互作用。在嗜性组内或组间，CD4⁺细胞斜率无显著差异。
即使采用454测序，血浆HIV-1嗜性似乎也不能增强CD4细胞计数和病毒载量预测艾滋病和死亡结局短期风险的能力。
