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Evaluating HIV testing strategies to reduce drug resistance during CAB-LA rollout in Thailand. a modelling study
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BACKGROUND: Long-acting cabotegravir (CAB-LA), an integrase strand transfer inhibitor (INSTI), is effective as pre-exposure prophylaxis (PrEP). CAB-LA delays HIV detection, allowing its continued use after HIV acquisition and increasing the risk of INSTI resistance mutations. Resistance to CAB-LA leads to cross-resistance with dolutegravir, a key drug in WHO-recommended HIV treatment regimens. CDC recommends sensitive antigen and RNA tests for timely HIV detection in CAB-LA users, but these tests are expensive and not widely available. We study the impact of testing strategies on HIV transmission and drug resistance after CAB-LA implementation.
METHODS: An HIV transmission model calibrated to the Thai HIV epidemic among men-who-have-sex-with-men (MSM) assumed an increase in PrEP users from the current 50,000-70,000 to 100,000 by 2034. CAB-LA use ranged from 0% to 100% of PrEP users by 2034. Literature indicated CAB-LA during HIV carries a 50%'100% risk of resistance development, and INSTI resistance reduces viral transmissibility by 30%'40%. The study compares CAB-LA implementation to the current situation (0%-5% resistance during viral failure with a dolutegravir containing regimen, no transmission of INSTI resistance). The model assumed CAB-LA use for one year with HIV testing every two months. Three HIV testing scenarios were assessed: 1) the most sensitive scenario in which all new infections are identified, and two less sensitive testing scenarios: 2) acute infections undetected, and 3) 50% of infections undiagnosed during the first year.
RESULTS: Without CAB-LA, 40,000 new infections occur between 2024 and 2034, and 524 individuals are expected to have INSTI drug resistance during viral failure with a dolutegravir containing regimen. CAB-LA can avert 1,600-6,200 infections (20%'100% uptake) but increases INSTI drug resistance cases by 28'94 individuals during viral failure (increase 5-18%) and by 4'15 individuals through transmitted INSTI resistance. More sensitive HIV testing reduced resistance during viral failure by 9'36 (reduction 32-38%) individuals and transmitted resistance by 2'6 individuals (40-50%).
CONCLUSIONS: CAB-LA introduction in Thailand can reduce new HIV infections but may simultaneously increase drug resistance to INSTIs. More sensitive HIV testing will prevent INSTI resistance. However, given the low INSTI resistance incidence, more sensitive testing is not critical for CAB-LA rollout.
METHODS: An HIV transmission model calibrated to the Thai HIV epidemic among men-who-have-sex-with-men (MSM) assumed an increase in PrEP users from the current 50,000-70,000 to 100,000 by 2034. CAB-LA use ranged from 0% to 100% of PrEP users by 2034. Literature indicated CAB-LA during HIV carries a 50%'100% risk of resistance development, and INSTI resistance reduces viral transmissibility by 30%'40%. The study compares CAB-LA implementation to the current situation (0%-5% resistance during viral failure with a dolutegravir containing regimen, no transmission of INSTI resistance). The model assumed CAB-LA use for one year with HIV testing every two months. Three HIV testing scenarios were assessed: 1) the most sensitive scenario in which all new infections are identified, and two less sensitive testing scenarios: 2) acute infections undetected, and 3) 50% of infections undiagnosed during the first year.
RESULTS: Without CAB-LA, 40,000 new infections occur between 2024 and 2034, and 524 individuals are expected to have INSTI drug resistance during viral failure with a dolutegravir containing regimen. CAB-LA can avert 1,600-6,200 infections (20%'100% uptake) but increases INSTI drug resistance cases by 28'94 individuals during viral failure (increase 5-18%) and by 4'15 individuals through transmitted INSTI resistance. More sensitive HIV testing reduced resistance during viral failure by 9'36 (reduction 32-38%) individuals and transmitted resistance by 2'6 individuals (40-50%).
CONCLUSIONS: CAB-LA introduction in Thailand can reduce new HIV infections but may simultaneously increase drug resistance to INSTIs. More sensitive HIV testing will prevent INSTI resistance. However, given the low INSTI resistance incidence, more sensitive testing is not critical for CAB-LA rollout.