The impact of analytical treatment interruptions and trial interventions on time to viral re-suppression in people living with HIV restarting ART in cure-related clinical studies: a systematic review and meta-analysis.
ATI
HIV
HIV cure
antiretroviral therapy
treatment interruption
viral suppression
Journal
Journal of the International AIDS Society
ISSN: 1758-2652
Titre abrégé: J Int AIDS Soc
Pays: Switzerland
ID NLM: 101478566
Informations de publication
Date de publication:
Aug 2024
Aug 2024
Historique:
received:
11
10
2023
accepted:
30
07
2024
medline:
19
8
2024
pubmed:
19
8
2024
entrez:
19
8
2024
Statut:
ppublish
Résumé
To assess the effectiveness of novel HIV curative strategies, "cure" trials require periods of closely monitored antiretroviral therapy (ART) analytical treatment interruptions (ATIs). We performed a systematic review and meta-analysis to identify the impact of ATI with or without novel therapeutics in cure-related studies on the time to viral re-suppression following ART restart. Medline, Embase and Web of Science databases were searched for human studies involving ATIs from 1 January 2015 till 22 April 2024. The primary outcome was time to first viral re-suppression (plasma HIV viral load [VL] <50 copies/ml) stratified by receipt of interventional drug with ATI (IA) or ATI-only groups. Random-effects proportional meta-analysis and multivariable Cox proportional hazards analysis were performed using R. Of 1073 studies screened, 13 were included that met the inclusion criteria with VL data available after restarting ART (n = 213 participants). There was no difference between time to viral suppression in IA or ATI-only cohorts (p = 0.22). For 87% of participants, viral suppression within 12 weeks of ART restart was achieved, and all eventually had at least one VL <50 copies/ml during follow-up. After adjusting for covariables, while participants in the IA cohort were associated with less rapid suppression (adjusted hazard ratio [aHR] 0.61, 95% CI 0.40-0.94, p = 0.026), other factors include greater log VL at ART restart (aHR 0.56, 95% CI 0.46-0.68, p<0.001), duration since HIV diagnosis (aHR 0.93, 95% CI 0.89-0.96) and longer intervals between HIV VL monitoring (aHR 0.66, 95% CI 0.59-0.74, p<0.001). However, the use of integrase inhibitors was associated with more rapid viral suppression (aHR 1.74, 95% CI 1.16-2.59). When designing studies involving ATIs, information on time to viral re-suppression after restarting ART is important to share with participants, and should be regularly monitored and reported, to assess the impact and safety of specific trial interventions in ATI studies. The majority of participants achieved viral suppression after restarting ART in ATI studies. ART regimens containing integrase inhibitors and frequent VL monitoring should be offered for people restarting ART after ATI studies to ensure rapid re-suppression.
Substances chimiques
Anti-HIV Agents
0
Types de publication
Journal Article
Systematic Review
Meta-Analysis
Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
e26349Subventions
Organisme : UK Medical Research Council
ID : MR/W024454/1
Informations de copyright
© 2024 The Author(s). Journal of the International AIDS Society published by John Wiley & Sons Ltd on behalf of International AIDS Society.
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