HIV-NAT, Thai Red Cross AIDS Research Centre and Centre of Excellence in Tuberculosis, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.
Center for Biostatistics in AIDS Research in the Department of Biostatistics, Harvard T H Chan School of Public Health, Boston, Massachusetts, USA.
J Int AIDS Soc. 2022 Jun;25(6):e25905. doi: 10.1002/jia2.25905.
ACTG A5288 was a strategy trial conducted in diverse populations from multiple continents of people living with HIV (PLWH) failing second-line protease inhibitor (PI)-based antiretroviral therapy (ART) from 10 low- and middle-income countries (LMICs). Participants resistant to lopinavir (LPV) and/or multiple nucleotide reverse transcriptase inhibitors started on third-line regimens that included raltegravir (RAL), darunavir/ritonavir (DRV/r) and/or etravirine (ETR) according to their resistance profiles. At 48 weeks, 87% of these participants achieved HIV-1 RNA ≤200 copies/ml. We report here long-term outcomes over 144 weeks.
Study participants were enrolled from 2013 to 2015, prior to the availability of dolutegravir in LMICs. "Extended Follow-up" of the study started after the last participant enrolled had reached 48 weeks and included participants still on antiretroviral (ARV) regimens containing RAL, DRV/r and/or ETR at that time. RAL, DRV/r and ETR were provided for an additional 96 weeks (giving total follow-up of ≥144 weeks), with HIV-1 RNA measured at 48 and 96 weeks and CD4 count at 96 weeks after entry into Extended Follow-up. Proportion of participants with HIV-1 RNA ≤200 copies/ml was estimated every 24 weeks, using imputation if necessary to handle the different measurement schedule in Extended Follow-up; mean CD4 count changes were estimated using loess regression.
Of 257 participants (38% females), at study entry, median CD4 count was 179 cells/mm , and HIV-1 RNA was 4.6 log copies/ml. Median follow-up was 168 weeks (IQR: 156-204); 15 (6%) participants were lost to follow-up and 9 (4%) died. 27/246 (11%), 26/246 (11%) and 13/92 (14%) of participants who started RAL, DRV/r and ETR, respectively, discontinued these drugs; only three due to adverse events. 87%, 86%, 83% and 80% of the participants had HIV-1 RNA ≤200 copies/ml at weeks 48, 96, 144 and 168 (95% CI at week 168: 74-85%), respectively. Mean increase from study entry in CD4 count at week 168 was 265 cells/mm (95% CI 247-283).
Third-line regimens comprising of RAL, DRV/r and/or ETR were very well tolerated and had high rates of durable virologic suppression among PLWH in LMICs who were failing on second-line PI-based ART prior to the availability of dolutegravir.
ACTG A5288 是一项在来自多个大洲的 10 个中低收入国家（LMICs）的接受二线基于蛋白酶抑制剂（PI）的抗逆转录病毒治疗（ART）失败的 HIV 感染者（PLWH）中进行的策略性试验。对洛匹那韦（LPV）和/或多种核苷酸逆转录酶抑制剂耐药的参与者，根据耐药情况，开始使用三线方案，其中包括拉替拉韦（RAL）、达芦那韦/利托那韦（DRV/r）和/或依曲韦林（ETR）。在第 48 周时，这些参与者中有 87%达到了 HIV-1 RNA ≤200 拷贝/ml。我们在此报告超过 144 周的长期结果。
研究参与者于 2013 年至 2015 年期间招募，当时洛匹那韦在 LMICs 尚未上市。该研究的“扩展随访”在最后一名参与者达到 48 周后开始，包括当时仍在使用包含 RAL、DRV/r 和/或 ETR 的抗逆转录病毒（ARV）方案的参与者。RAL、DRV/r 和 ETR 提供了另外 96 周的治疗（随访时间总计≥144 周），在第 48 周和第 96 周时测量 HIV-1 RNA，并在进入扩展随访后第 96 周时测量 CD4 计数。使用 imputation（如有必要）来处理扩展随访中不同的测量时间表，每 24 周估计一次 HIV-1 RNA ≤200 拷贝/ml 的参与者比例；使用 loess 回归估计平均 CD4 计数变化。
在 257 名参与者（38%为女性）中，在研究开始时，中位数 CD4 计数为 179 个细胞/mm ，HIV-1 RNA 为 4.6 log 拷贝/ml。中位随访时间为 168 周（IQR：156-204）；15 名（6%）参与者失访，9 名（4%）死亡。开始使用 RAL、DRV/r 和 ETR 的 27/246（11%）、26/246（11%）和 13/92（14%）名参与者分别停止了这些药物的治疗；仅有 3 名因不良事件停药。在第 48、96、144 和 168 周时，分别有 87%、86%、83%和 80%的参与者 HIV-1 RNA ≤200 拷贝/ml（第 168 周时的 95% CI：74-85%）。在第 168 周时，CD4 计数从研究开始时的平均增加量为 265 个细胞/mm（95% CI 247-283）。
在洛匹那韦上市之前，在接受二线基于蛋白酶抑制剂的 ART 失败的 LMICs 中，包含 RAL、DRV/r 和/或 ETR 的三线方案具有很好的耐受性，并且具有很高的持久病毒学抑制率。
