Virologic outcomes in early antiretroviral treatment: HPTN 052

Introduction: The HIV Prevention Trials Network (HPTN) 052 trial demonstrated that early antiretroviral therapy (ART) prevented 93% of HIV transmission events in serodiscordant couples. Some linked infections were observed shortly after ART initiation or after virologic failure. Objective: To evaluate factors associated with time to viral suppression and virologic failure in participants who initiated ART in HPTN 052. Methods: 1566 participants who had a viral load (VL) > 400 copies/mL at enrollment were included in the analyses. This included 832 in the early ART arm (CD4 350–550 cells/mm3 at ART initiation) and 734 in the delayed ART arm (204 with a CD4 3 at ART initiation; 530 with any CD4 at ART initiation). Viral suppression was defined as two consecutive VLs ≤ 400 copies/mL after ART initiation; virologic failure was defined as two consecutive VLs > 1000 copies/mL > 24 weeks after ART initiation. Results: Overall, 93% of participants achieved viral suppression by 12 months. The annual incidence of virologic failure was 3.6%. Virologic outcomes were similar in the two study arms. Longer time to viral suppression was associated with younger age, higher VL at ART initiation, and region (Africa vs. Asia). Virologic failure was strongly associated with younger age, lower educational level, and lack of suppression by three months; lower VL and higher CD4 at ART initiation were also associated with virologic failure. Conclusions: Several clinical and demographic factors were identified that were associated with longer time to viral suppression and virologic failure. Recognition of these factors may help optimize ART for HIV treatment and prevention.

引言：艾滋病预防试验网络（HIV Prevention Trials Network, HPTN）052临床试验结果显示，早期抗反转录病毒治疗（antiretroviral therapy, ART）可使单阳夫妇间93%的HIV传播事件得到预防。部分HIV传播感染可在ART启动后短期内或病毒学失败后被检出。研究目的：本研究旨在评估HPTN 052临床试验中接受ART的受试者，其病毒学抑制达标时间及病毒学失败的相关影响因素。研究方法：本分析纳入1566名入组时病毒载量（viral load, VL）＞400拷贝/毫升的受试者。其中早期ART组832名，受试者ART启动时CD4细胞计数为350~550个/mm³；延迟ART组734名，包括204名ART启动时CD4细胞计数为3个/mm³的受试者，以及530名ART启动时CD4细胞计数无特定限制的受试者。病毒学抑制定义为ART启动后连续两次VL检测结果≤400拷贝/毫升；病毒学失败定义为ART启动24周后连续两次VL检测结果＞1000拷贝/毫升。研究结果：整体而言，93%的受试者在12个月内实现了病毒学抑制。病毒学失败的年发生率为3.6%。两组受试者的病毒学结局无明显差异。病毒学抑制达标时间较长与年龄较小、ART启动时VL更高、地区差异（非洲vs.亚洲）显著相关。病毒学失败则与年龄较小、受教育程度较低、3个月时未实现病毒学抑制强相关；ART启动时VL较低、CD4细胞计数较高同样与病毒学失败相关。研究结论：本研究明确了数项与病毒学抑制达标时间延长及病毒学失败相关的临床及人口学因素。识别此类因素有助于优化HIV治疗与预防领域的ART方案。