The potential role of long-acting injectable cabotegravir-rilpivirine in the treatment of HIV in sub-Saharan Africa: a modelling analysis.
The potential role of long-acting injectable cabotegravir-rilpivirine in the treatment of HIV in sub-Saharan Africa: a modelling analysis.
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DOI：
10.1016/s2214-109x(21)00025-5
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发表时间：
2021-05
期刊：
影响因子：
--
通讯作者：
Garnett GP
中科院分区：
文献类型：
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作者：
Phillips AN;Bansi-Matharu L;Cambiano V;Ehrenkranz P;Serenata C;Venter F;Pett S;Flexner C;Jahn A;Revill P;Garnett GP
整合酶抑制剂卡博特韦和非核苷逆转录酶抑制剂利匹韦林的长效注射剂组合被认为是撒哈拉以南非洲艾滋病毒感染者的抗逆转录病毒治疗选择。我们的目的是对注射用卡博特韦-利匹韦林的效果进行建模，以帮助了解其在不同可能的引入政策下的潜在有效性和成本效益。我们使用现有的基于个体的艾滋病毒模型来预测每月注射卡博特韦-利匹韦林对撒哈拉以南非洲低收入地区艾滋病毒感染者的影响。我们在 1000 种情景背景下评估了政策，这些情景反映了撒哈拉以南非洲地区艾滋病毒流行和项目的特征。我们比较了引入注射卡博特韦-利匹韦林与继续使用基于多替拉韦的口服方案的三种政策：所有接受抗逆转录病毒治疗（ART）的个体；最近测量的病毒载量超过每毫升 1000 个拷贝的个体（表明口服药物依从性差，并且通常与耐药性相关）；最近测量的病毒载量低于每毫升 1000 个拷贝的个体（预先存在耐药性发生率较低的群体）。我们还进行了成本效益分析，从 10 年期间的卫生系统角度出发，对伤残调整生命年 (DALY) 和成本进行 3% 的折扣。每次避免伤残调整生命年 500 美元的成本效益阈值用于确定政策是否具有成本效益。在我们的模型中，所有涉及注射卡博特韦-利匹韦林的政策预计都会导致接受抗逆转录病毒治疗的艾滋病毒感染者比例增加，病毒载量抑制增加，艾滋病相关死亡率下降，而对于最近测量的病毒载量低于每毫升1000拷贝的人来说，获益较小。如果将其引入所有接受 ART 的 HIV 感染者或最近测量的病毒载量低于 1000 拷贝/mL 的人群中，预计也会导致对整合酶抑制剂和非核苷逆转录酶抑制剂的耐药性增加，但如果引入到病毒载量超过 1000 拷贝/mL 的人群中，则影响程度较小，因为其使用集中在不太坚持口服治疗的人群中。与对艾滋病相关死亡率的影响一致，所有引入注射卡博特韦-利匹韦林的方法预计都可以避免伤残调整生命年。假设每人每年的成本为 120 美元，对于最近测量的病毒载量超过 1000 拷贝/毫升的人来说，使用该方案是划算的（在设定方案中每个 DALY 避免的中位成本为 404 美元）。除非注射用卡博特韦-利匹韦林每年的成本大幅降低，否则考虑使用的其他方法不太可能具有成本效益。我们的模型表明，注射用卡博特韦-利匹韦林具有潜在的益处；然而，为了成为一种具有成本效益的选择，它的引入可能需要仔细针对艾滋病毒感染者，否则这些人可能无法达到最佳的抗逆转录病毒治疗依从性。随着试验和实施研究中数据的积累，这些发现可以纳入模型中，以更好地了解政策选择的全部后果。比尔及梅琳达·盖茨基金会，包括通过 HIV 模型联盟 (OPP1191655)。
The use of a combination of the integrase inhibitor, cabotegravir, and the non-nucleoside reverse transcriptase inhibitor, rilpivirine, in a long-acting injectable form is being considered as an antiretroviral treatment option for people with HIV in sub-Saharan Africa. We aimed to model the effects of injectable cabotegravir–rilpivirine to help to inform its potential effectiveness and cost-effectiveness under different possible policies for its introduction. We used an existing individual-based model of HIV to predict the effects of introducing monthly injections of cabotegravir–rilpivirine for people with HIV in low-income settings in sub-Saharan Africa. We evaluated policies in the context of 1000 setting scenarios that reflected characteristics of HIV epidemics and programmes in sub-Saharan Africa. We compared three policies for introduction of injectable cabotegravir–rilpivirine with continued use of dolutegravir-based oral regimens for: all individuals on antiretroviral therapy (ART); individuals with a recently measured viral load of more than 1000 copies per mL (signifying poor adherence to oral drugs, and often associated with drug resistance); and individuals with a recently measured viral load of less than 1000 copies per mL (a group with a lower prevalence of pre-existing drug resistance). We also did cost-effectiveness analysis, taking a health system perspective over a 10 year period, with 3% discounting of disability-adjusted life-years (DALYs) and costs. A cost-effectiveness threshold of US$500 per DALY averted was used to establish if a policy was cost-effective. In our model, all policies involving the introduction of injectable cabotegravir–rilpivirine were predicted to lead to an increased proportion of people with HIV on ART, increased viral load suppression, and decreased AIDS-related mortality, with lesser benefits in people with a recently measured viral load of less than 1000 copies per mL. Its introduction is also predicted to lead to increases in resistance to integrase inhibitors and non-nucleoside reverse transcriptase inhibitors if introduced in all people with HIV on ART or in those with a recently measured viral load of less than 1000 copies per mL, but to a lesser extent if introduced in people with more than 1000 copies per mL due to concentration of its use in people less adherent to oral therapy. Consistent with the effect on AIDS-related mortality, all approaches to the introduction of injectable cabotegravir–rilpivirine are predicted to avert DALYs. Assuming a cost of $120 per person per year, use of this regimen in people with a recently measured viral load of more than 1000 copies per mL was borderline cost-effective (median cost per DALY averted across setting scenarios $404). The other approaches considered for its use are unlikely to be cost-effective unless the cost per year of injectable cabotegravir–rilpivirine is considerably reduced. Our modelling suggests that injectable cabotegravir–rilpivirine offers potential benefits; however, to be a cost-effective option, its introduction might need to be carefully targeted to individuals with HIV who might otherwise have suboptimal adherence to ART. As data accumulate from trials and implementation studies, such findings can be incorporated into the model to better inform on the full consequences of policy alternatives. Bill & Melinda Gates Foundation, including through the HIV Modelling Consortium (OPP1191655).