ArticleEBioMedicine2024
Temporary increase in circulating replication-competent latent HIV-infected resting CD4+ T cells after switch to an integrase inhibitor based antiretroviral regimen.
Article in EBioMedicine, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
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Who cites it
5 citing papers in PubMed.
- In-depth Analysis of the HIV Reservoir Confirms Effectiveness and Safety of Dolutegravir/Lamivudine in a Phase 4 Randomized Controlled Switch Trial (RUMBA).The Journal of infectious diseases · 2025Trial
- Estimating HIV-1 Viremic Time From Reservoir Sequence Diversity With Uncertainty Quantification.The Journal of infectious diseases · 2026Article
- Article
- Development and validation of HIV SMRTcap for the characterization of HIV-1 reservoirs across tissues and subtypes.PLoS pathogens · 2026Article
- Association between HIV-1 Nef-mediated MHC-I downregulation and the maintenance of the replication-competent latent viral reservoir in individuals with virally suppressed HIV-1 in Uganda: an exploratory cohort study.The Lancet. Microbe · 2025Article
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27 authors.
Funding
Abstract
backgroundThe principal barrier to an HIV cure is the presence of the latent viral reservoir (LVR), which has been understudied in African populations. From 2018 to 2019, Uganda instituted a nationwide rollout of ART consisting of Dolutegravir (DTG) with two NRTI, which replaced the previous regimen of one NNRTI and the same two NRTI.
methodsChanges in the inducible replication-competent LVR (RC-LVR) of ART-suppressed Ugandans with HIV (n = 88) from 2015 to 2020 were examined using the quantitative viral outgrowth assay. Outgrowth viruses were examined for viral evolution. Changes in the RC-LVR were analyzed using three versions of a Bayesian model that estimated the decay rate over time as a single, linear rate (model A), or allowing for a change at time of DTG initiation (model B&C).
findingsModel A estimated the slope of RC-LVR change as a non-significant positive increase, which was due to a temporary spike in the RC-LVR that occurred 0-12 months post-DTG initiation (p < 0.005). This was confirmed with models B and C; for instance, model B estimated a significant decay pre-DTG initiation with a half-life of 6.9 years, and an ∼1.7-fold increase in the size of the RC-LVR post-DTG initiation. There was no evidence of viral failure or consistent evolution in the cohort.
interpretationThese data suggest that the change from NNRTI- to DTG-based ART is associated with a significant temporary increase in the circulating RC-LVR.
fundingSupported by the NIH (grant 1-UM1AI164565); Gilead HIV Cure Grants Program (90072171); Canadian Institutes of Health Research (PJT-155990); and Ontario Genomics-Canadian Statistical Sciences Institute.
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