Dolutegravir for first-line antiretroviral therapy in low-income and middle-income countries: uncertainties and opportunities for implementation and research
Dolutegravir for first-line antiretroviral therapy in low-income and middle-income countries: uncertainties and opportunities for implementation and research
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DOI：
10.1016/s2352-3018(18)30093-6
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发表时间：
2018-07-01
期刊：
影响因子：
16.1
通讯作者：
Garrett, Nigel
中科院分区：
文献类型：
--
作者：
Dorward, Jienchi;Lessells, Richard;Garrett, Nigel
一种新的一线抗逆转录病毒疗法（ART）方案包含dolutegravir正在低收入和中等收入国家（LMIC）推出。在主要来自高收入环境的研究中，与现有的一线治疗方案相比，基于度鲁特韦的治疗方案具有更好的上级疗效、耐受性和持久性。然而，在中低收入国家推广度鲁特韦仍存在一些问题，这些国家的大多数艾滋病毒感染者是育龄妇女，结核病流行率可能很高，获得病毒载量和艾滋病毒耐药性检测的机会有限。队列研究的结果表明，在怀孕期间开始使用度鲁特韦是安全的，但需要更多的数据来确定在怀孕前开始使用度鲁特韦方案时不良出生结局的风险。增加获得病毒载量检测以监测dolutegravir的有效性仍然至关重要，但管理病毒血症患者的最佳策略尚不清楚。此外，支持度鲁特韦与结核病治疗联合使用的有效性的证据很少，特别是在中低收入国家的方案环境中。最后，核苷类逆转录酶抑制剂耐药是否会影响以度鲁特韦为基础的方案在一线和潜在二线ART中的长期疗效尚不清楚。临床试验、队列研究和艾滋病毒耐药性监测将是回答这些问题和最大限度地发挥这种新方案的益处所必需的。
A new first-line antiretroviral therapy (ART) regimen containing dolutegravir is being rolled out in low-income and middle-income countries (LMICs). In studies from predominantly high-income settings, dolutegravir-based regimens had superior efficacy, tolerability, and durability compared with existing first-line regimens. However, several questions remain about the roll out of dolutegravir in LMICs, where most people with HIV are women of reproductive age, tuberculosis prevalence can be high, and access to viral load and HIV drug resistance testing is limited. Findings from cohort studies suggest that dolutegravir is safe when initiated in pregnancy, but more data are needed to determine the risk of adverse birth outcomes when dolutegravir-based regimens are initiated before conception. Increasing access to viral load testing to monitor the effectiveness of dolutegravir remains crucial, but the best strategy to manage patients with viraemia is unclear. Furthermore, evidence to support the effectiveness of dolutegravir when given with tuberculosis treatment is scarce, particularly in programmatic settings in LMICs. Lastly, whether nucleoside reverse transcriptase inhibitor resistance will affect the long-term efficacy of dolutegravir-based regimens in first-line, and potentially second-line, ART is unknown. Clinical trials, cohorts, and surveillance of HIV drug resistance will be necessary to answer these questions and to maximise the benefits of this new regimen.