The effect of long-acting cabotegravir and rilpivirine treatment on drug resistance in South Africa: a modelling study

作者：Nuri Han, Tom Loosli, Nanina Anderegg, Anthony Hauser, Johannes Josi, Mary‐Ann Davies, Leigh F. Johnson, Richard Lessells, Huldrych F. Günthard, Matthias Egger, Roger D. Kouyos · 发表于：The Lancet Global Health · 年份：2025 · DOI：10.1016/s2214-109x(25)00350-x · 被引用次数：3 · 研究领域：HIV/AIDS drug development and treatment、Influenza Virus Research Studies、Pharmaceutical Quality and Counterfeiting

BACKGROUND: Long-acting injectable cabotegravir and rilpivirine (LAI cabotegravir and rilpivirine) is recommended as maintenance therapy for people living with HIV who achieved viral suppression on oral antiretroviral therapy (ART). However, its effect on drug resistance evolution in resource-limited settings remains uncertain. We aimed to assess this effect under different roll-out strategies and explore key factors for resistance. METHODS: We extended the Modelling Antiretroviral Drug Resistance In South Africa (MARISA) model to assess the effect of introducing LAI cabotegravir and rilpivirine in South Africa from 2025 to 2045. The HIV transmission rate was recalibrated using incidence estimates from the Thembisa model. We considered three strategies: dolutegravir-based ART as per current guidelines; LAI cabotegravir and rilpivirine as a switching option for those with viral suppression; and LAI cabotegravir and rilpivirine for both switching and ART initiation. We assumed faster development of integrase strand transfer inhibitor (INSTI) resistance in individuals with viraemia (≥1000 copies/mL) on LAI cabotegravir and rilpivirine than those with viraemia on dolutegravir-based ART. We evaluated their effect on pre-treatment drug resistance (PDR) and transmitted drug resistance (TDR) for INSTI and rilpivirine, explored resistance mitigation strategies, and identified key uncertainties through one-at-a-time local and global sensitivity analyses. FINDINGS: By 2045, using LAI ca...