ArticleThe Lancet. Global health2025
The effect of long-acting cabotegravir and rilpivirine treatment on drug resistance in South Africa: a modelling study.
Article in The Lancet. Global health, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers, 1 of them a synthesis that pooled it.
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Who cites it
2 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Simulation modeling for the design and evaluation of HIV drug resistance interventions: a systematic review of literature.BMC public health · 2026Pooled it
- The multifaceted antiretroviral coverage provided by BIC/FTC/TAF: a pharmacokinetic/pharmacodynamic revisitation.Le infezioni in medicina · 2026Review
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Authors and funding
11 authors.
Funding
Abstract
backgroundLong-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.
methodsWe 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.
findingsBy 2045, using LAI cabotegravir and rilpivirine for both switching and ART initiation was estimated to lead to higher INSTI resistance levels, with 30·6% INSTI PDR and 11·3% INSTI TDR at 30% LAI cabotegravir and rilpivirine coverage, compared with 14·0% INSTI PDR and 6·9% INSTI TDR with continued oral dolutegravir-based ART. Rilpivirine resistance under the LAI cabotegravir and rilpivirine initiation and switch strategy was estimated to increase to 41·0% PDR and 30·0% TDR, compared with 6·7% and 4·5% with oral dolutegravir-based ART. Resistance levels were similar for LAI cabotegravir and rilpivirine as a switching option for those with viral suppression. A course of oral ART after LAI cabotegravir and rilpivirine interruption (oral bridging) decreased the risk of drug resistance due to the long pharmacokinetic tail, resulting in 22·3% INSTI PDR and 26·0% rilpivirine PDR when using LAI cabotegravir and rilpivirine for both switching and ART initiation. Key factors influencing resistance levels were care disengagement rates, LAI cabotegravir and rilpivirine coverage, and INSTI mutation reversion rates.
interpretationLAI cabotegravir and rilpivirine roll-out in South Africa should be cautious and targeted. Resistance risks may be mitigated through pre-treatment resistance testing, close monitoring of treatment outcomes, and efforts to increase retention in care.
fundingUS National Institutes of Health National Institute of Allergy and Infectious Diseases and the Swiss National Science Foundation.
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