Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD.
Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA.
J Acquir Immune Defic Syndr. 2018 Apr 15;77(5):484-491. doi: 10.1097/QAI.0000000000001623.
We evaluated HIV drug resistance in adults who received early vs. delayed antiretroviral therapy (ART) in a multinational trial [HIV Prevention Trials Network (HPTN) 052, enrollment 2005-2010]. In HPTN 052, 1763 index participants were randomized to start ART at a CD4 cell count of 350-550 cells/mm (early ART arm) or <250 cells/mm (delayed ART arm). In May 2011, interim study results showed benefit of early ART, and all participants were offered ART regardless of CD4 cell count; the study ended in 2015.
Virologic failure was defined as 2 consecutive viral loads >1000 copies/mL >24 weeks after ART initiation. Drug resistance testing was performed for pretreatment (baseline) and failure samples from participants with virologic failure.
HIV genotyping results were obtained for 211/249 participants (128 early ART arm and 83 delayed ART arm) with virologic failure. Drug resistance was detected in 4.7% of participants at baseline; 35.5% had new resistance at failure. In univariate analysis, the frequency of new resistance at failure was lower among participants in the early ART arm (compared with delayed ART arm, P = 0.06; compared with delayed ART arm with ART initiation before May 2011, P = 0.032). In multivariate analysis, higher baseline viral load (P = 0.0008) and ART regimen (efavirenz/lamivudine/zidovudine compared with other regimens, P = 0.024) were independently associated with higher risk of new resistance at failure.
In HPTN 052, the frequency of new drug resistance at virologic failure was lower in adults with early ART initiation. The main factor associated with reduced drug resistance with early ART was lower baseline viral load.
我们评估了在一项多国试验[HIV 预防试验网络（HPTN）052，入组时间 2005-2010]中接受早期与延迟抗逆转录病毒治疗（ART）的成年人中的 HIV 耐药情况。在 HPTN 052 中，1763 名指数参与者被随机分配在 CD4 细胞计数为 350-550 个细胞/mm（早期 ART 组）或 <250 个细胞/mm（延迟 ART 组）时开始 ART。2011 年 5 月，中期研究结果显示早期 ART 有益，所有参与者均提供 ART，无论 CD4 细胞计数如何；该研究于 2015 年结束。
病毒学失败定义为在开始 ART 后 24 周内连续两次病毒载量>1000 拷贝/mL。对病毒学失败参与者的治疗前（基线）和失败样本进行了耐药性检测。
对 211/249 名病毒学失败参与者（早期 ART 组 128 名，延迟 ART 组 83 名）获得了 HIV 基因分型结果。基线时发现 4.7%的参与者存在耐药性；失败时 35.5%有新的耐药性。单因素分析显示，早期 ART 组失败时新耐药的频率较低（与延迟 ART 组相比，P=0.06；与 2011 年 5 月前开始 ART 的延迟 ART 组相比，P=0.032）。多因素分析显示，基线病毒载量较高（P=0.0008）和 ART 方案（依非韦伦/拉米夫定/齐多夫定与其他方案相比，P=0.024）与失败时新耐药的风险增加独立相关。
在 HPTN 052 中，早期开始 ART 的成年人中病毒学失败时新耐药的频率较低。与早期 ART 相关的降低耐药性的主要因素是较低的基线病毒载量。
