撒哈拉以南非洲地区基于多替拉韦的抗逆转录病毒药物方案的风险和获益：一项建模研究。

Risks and benefits of dolutegravir-based antiretroviral drug regimens in sub-Saharan Africa: a modelling study.

机构信息

University College London, London, UK.

Wits Reproductive Health and HIV Institute, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.

出版信息

Lancet HIV. 2019 Feb;6(2):e116-e127. doi: 10.1016/S2352-3018(18)30317-5. Epub 2018 Nov 29.

DOI:10.1016/S2352-3018(18)30317-5

PMID:30503325

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6361866/

Abstract

BACKGROUND

The integrase inhibitor dolutegravir could have a major role in future antiretroviral therapy (ART) regimens in sub-Saharan Africa because of its high potency and barrier to resistance, good tolerability, and low cost, but there is uncertainty over appropriate policies for use relating to the potential for drug resistance spread and a possible increased risk of neural tube defects in infants if used in women at the time of conception. We used an existing individual-based model of HIV transmission, progression, and the effect of ART with the aim of informing policy makers on approaches to the use of dolutegravir that are likely to lead to the highest population health gains.

METHODS

We used an existing individual-based model of HIV transmission and progression in adults, which takes into account the effects of drug resistance and differential drug potency in determining viral suppression and clinical outcomes to compare predicted outcomes of alternative ART regimen policies. We calculated disability adjusted life-years (DALYs) for each policy, assuming that a woman having a child with a neural tube defect incurs an extra DALY per year for the remainder of the time horizon and accounting for mother-to-child transmission. We used a 20 year time horizon, a 3% discount rate, and a cost-effectiveness threshold of US$500 per DALY averted.

FINDINGS

The greatest number of DALYs is predicted to be averted with use of a policy in which tenofovir, lamivudine, and dolutegravir is used in all people on ART, including switching to tenofovir, lamivudine, and dolutegravir in those currently on ART, regardless of current viral load suppression and intention to have (more) children. This result was consistent in several sensitivity analyses. We predict that this policy would be cost-saving.

INTERPRETATION

Using a standard DALY framework to compare health outcomes from a public health perspective, the benefits of transition to tenofovir, lamivudine, and dolutegravir for all substantially outweighed the risks.

FUNDING

Bill & Melinda Gates Foundation.

摘要

背景

整合酶抑制剂多拉韦林由于其高效性和耐药屏障、良好的耐受性以及低成本，在撒哈拉以南非洲的未来抗逆转录病毒疗法（ART）方案中可能发挥重要作用，但对于与耐药性传播的潜在风险相关的使用相关政策存在不确定性，如果在受孕时用于女性，可能会增加婴儿神经管缺陷的风险。我们使用现有的 HIV 传播、进展和 ART 效果的个体为基础的模型，旨在为决策者提供关于使用多拉韦林的方法，这些方法可能会带来最高的人群健康收益。

方法

我们使用现有的成人 HIV 传播和进展的个体为基础的模型，该模型考虑了耐药性的影响和不同药物的效力，以确定病毒抑制和临床结果，从而比较替代 ART 方案政策的预测结果。我们为每个政策计算了残疾调整生命年（DALY），假设一个患有神经管缺陷的孩子的母亲在时间范围内的剩余时间每年会增加一个额外的 DALY，并考虑了母婴传播。我们使用 20 年的时间范围、3%的贴现率和每避免一个 DALY 500 美元的成本效益阈值。