抗逆转录病毒治疗失败的非洲撒哈拉以南地区艾滋病病毒 1 型感染者应用蛋白酶抑制剂/核苷（酸）逆转录酶抑制剂二线方案的疗效：系统评价和荟萃分析。
Effectiveness of Protease Inhibitor/Nucleos(t)ide Reverse Transcriptase Inhibitor-Based Second-line Antiretroviral Therapy for the Treatment of Human Immunodeficiency Virus Type 1 Infection in Sub-Saharan Africa: A Systematic Review and Meta-analysis.
机构信息
Malawi-Liverpool-Wellcome Trust Clinical Research Programme, Blantyre.
Institute of Infection and Global Health, University of Liverpool.
出版信息
Clin Infect Dis. 2018 Jun 1;66(12):1846-1857. doi: 10.1093/cid/cix1108.
BACKGROUND
In sub-Saharan Africa, 25.5 million people are living with human immunodeficiency virus (HIV), representing 70% of the global total. The need for second-line antiretroviral therapy (ART) is projected to increase in the next decade in keeping with the expansion of treatment provision. Outcome data are required to inform policy.
METHODS
We performed a systematic review and meta-analysis of studies reporting the virological outcomes of protease inhibitor (PI)-based second-line ART in sub-Saharan Africa. The primary outcome was virological suppression (HIV-1 RNA <400 copies/mL) after 48 and 96 weeks of treatment. The secondary outcome was the proportion of patients with PI resistance. Pooled aggregate data were analyzed using a DerSimonian-Laird random effects model.
RESULTS
By intention-to-treat analysis, virological suppression occurred in 69.3% (95% confidence interval [CI], 58.2%-79.3%) of patients at week 48 (4558 participants, 14 studies), and in 61.5% (95% CI, 47.2%-74.9%) at week 96 (2145 participants, 8 studies). Preexisting resistance to nucleos(t)ide reverse transcriptase inhibitors (NRTIs) increased the likelihood of virological suppression. Major protease resistance mutations occurred in a median of 17% (interquartile range, 0-25%) of the virological failure population and increased with duration of second-line ART.
CONCLUSIONS
One-third of patients receiving PI-based second-line ART with continued NRTI use in sub-Saharan Africa did not achieve virological suppression, although among viremic patients, protease resistance was infrequent. Significant challenges remain in implementation of viral load monitoring. Optimizing definitions and strategies for management of second-line ART failure is a research priority.
PROSPERO REGISTRATION
CRD42016048985.
背景
在撒哈拉以南非洲地区，有 2550 万人感染了人类免疫缺陷病毒（HIV），占全球总数的 70%。预计未来十年，随着治疗范围的扩大，对二线抗逆转录病毒治疗（ART）的需求将会增加。为了制定政策，需要有疗效数据作为参考。
方法
我们对在撒哈拉以南非洲地区进行的以蛋白酶抑制剂（PI）为基础的二线 ART 治疗病毒学结果的研究进行了系统回顾和荟萃分析。主要结局是治疗 48 周和 96 周后的病毒学抑制（HIV-1 RNA<400 拷贝/ml）。次要结局是 PI 耐药的患者比例。采用 DerSimonian-Laird 随机效应模型对汇总数据进行分析。
结果
根据意向治疗分析，48 周时，4558 名患者（14 项研究）中有 69.3%（95%置信区间[CI]，58.2%-79.3%）达到病毒学抑制，2145 名患者（8 项研究）在 96 周时达到 61.5%（95% CI，47.2%-74.9%）。对核苷（酸）逆转录酶抑制剂（NRTIs）的预先存在耐药性增加了病毒学抑制的可能性。主要蛋白酶耐药突变发生在病毒学失败人群中的中位数为 17%（四分位距，0-25%），并且随着二线 ART 的持续时间而增加。
结论
在撒哈拉以南非洲地区，接受以 PI 为基础的二线 ART 治疗并继续使用 NRTI 的患者中，有三分之一未达到病毒学抑制，但在病毒血症患者中，蛋白酶耐药性并不常见。在实施病毒载量监测方面仍面临重大挑战。优化二线 ART 治疗失败的定义和管理策略是研究的重点。
PROSPERO 注册号：CRD42016048985。
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