Universidade Federal do Pampa - Campus Uruguaiana, Administrative Building, Collective Room No. 2, BR 472, Km 592 - Caixa Postal 118, Uruguaiana, RS, Brazil.
Statistics Department, Hospital de Clínicas de Porto Alegre, Universidade Federal Do Rio Grande Do Sul, Rua Ramiro Barcelos, Porto Alegre, RS, 2350, Brazil.
Syst Rev. 2022 Nov 17;11(1):243. doi: 10.1186/s13643-022-02102-3.
The World Health Organization (WHO) has identified the need for evidence on third-line antiretroviral therapy (ART) for adults living with HIV/AIDS, given that some controversy remains as to the best combinations of ART for experienced HIV-1-infected patients. Therefore, we conducted a systematic review and meta-analysis to (i) assess the efficacy of third-line therapy for adults with HIV/AIDS based on randomized controlled trials (RCT) that adopted the "new antiretroviral (ARV) + optimized background therapy (OBT)" approach and (ii) address the key issues identified in WHO's guidelines on the use of third-line therapy.
MEDLINE, EMBASE, LILACS, ISI Web of Science, SCOPUS, and Cochrane Central Register of Controlled Trials were searched for RCTs assessing third-line ARV therapy that used an OBT approach between 1966 and 2015. Data was extracted using an Excel-structured datasheet based on the Consolidated Standards of Reporting Trials (CONSORT) recommendations. The primary outcome of this meta-analysis was the proportion of patients reaching undetectable HIV RNA levels (< 50 copies/mL) at 48 weeks of follow-up. Included studies were evaluated using the Cochrane's Risk of Bias assessment tool. Summarized evidence was rated according to the GRADE approach.
Eighteen trials assessing 9 new ARV + OBT combinations defined as third-line HIV therapy provided the efficacy data: 7 phase IIb trials and 11 phase III trials. Four of the 18 trials provided extension data, thus resulting in 14 trials providing 48-week efficacy data. In the meta-analysis, considering the outcome regarding the proportion of patients with a viral load below 50 copies/ml at 48 weeks, 9 out of 14 trials demonstrated the superiority of the new combination being studied (risk difference = 0.18, 95% CI 0.13-0.23). The same analysis stratified by the number of fully active ARVs demonstrated a risk difference of 0.29 (95% CI 0.12-0.46), 0.28 (95% CI 0.17-0.38) and 0.17 (95% CI 0.10-0.24) respectively from zero, one, and two or more active drugs strata. Nine of the 18 trials were considered to have a high risk of bias.
Efficacy results demonstrated that the groups of HIV-experienced patients receiving the new ARV + OBT were more likely to achieve viral suppression when compared to the control groups. However, most of these trials may be at a high risk of bias. Thus, there is still not enough evidence to stipulate which combinations are the most effective for therapeutic regimens that are to be used sequentially due to documented multi-resistance.
世界卫生组织（WHO）已确定需要针对成人艾滋病毒/艾滋病患者的三线抗逆转录病毒疗法（ART）提供证据，因为对于经验丰富的 HIV-1 感染者的最佳 ART 组合仍存在一些争议。因此，我们进行了一项系统评价和荟萃分析，以（i）评估基于采用“新的抗逆转录病毒（ARV）+优化的背景治疗（OBT）”方法的随机对照试验（RCT）的三线疗法对成人 HIV/AIDS 的疗效，以及（ii）解决 WHO 关于三线疗法使用指南中确定的关键问题。
我们在 1966 年至 2015 年间检索了评估采用 OBT 方法的三线 ARV 治疗的 RCT，检索了 MEDLINE、EMBASE、LILACS、ISI Web of Science、SCOPUS 和 Cochrane 对照试验中心注册数据库。使用基于 CONSORT 建议的 Excel 结构数据表提取数据。本荟萃分析的主要结局是在 48 周随访时达到不可检测的 HIV RNA 水平（<50 拷贝/毫升）的患者比例。使用 Cochrane 偏倚风险评估工具评估纳入的研究。根据 GRADE 方法对汇总证据进行分级。
18 项评估 9 种新的 ARV+OBT 组合的 RCT 提供了疗效数据：7 项 IIb 期试验和 11 项 III 期试验。其中 4 项试验提供了扩展数据，因此有 14 项试验提供了 48 周的疗效数据。在荟萃分析中，考虑到 48 周时病毒载量低于 50 拷贝/ml 的患者比例的结局，14 项试验中有 9 项显示研究中的新组合具有优越性（风险差异=0.18，95%CI 0.13-0.23）。按完全有效的 ARV 数量分层的相同分析显示，从无活性药物到单药和两药或更多活性药物，风险差异分别为 0.29（95%CI 0.12-0.46）、0.28（95%CI 0.17-0.38）和 0.17（95%CI 0.10-0.24）。18 项试验中有 9 项被认为具有高偏倚风险。
疗效结果表明，与对照组相比，接受新的 ARV+OBT 的经验丰富的 HIV 患者组更有可能实现病毒抑制。然而，由于记录的多重耐药性，大多数这些试验可能存在高偏倚风险。因此，由于存在文档记录的多重耐药性，仍然没有足够的证据来规定哪些组合对连续使用的治疗方案最有效。
