Definition of Virological Endpoints Improving the Design of Human Immunodeficiency Virus (HIV) Cure Strategies Using Analytical Antiretroviral Treatment Interruption
PRAGUE, Melanie
Statistics In System biology and Translational Medicine [SISTM]
Bordeaux population health [BPH]
Statistics In System biology and Translational Medicine [SISTM]
Bordeaux population health [BPH]
LHOMME, Edouard
Statistics In System biology and Translational Medicine [SISTM]
Bordeaux population health [BPH]
See more >
Statistics In System biology and Translational Medicine [SISTM]
Bordeaux population health [BPH]
PRAGUE, Melanie
Statistics In System biology and Translational Medicine [SISTM]
Bordeaux population health [BPH]
Statistics In System biology and Translational Medicine [SISTM]
Bordeaux population health [BPH]
LHOMME, Edouard
Statistics In System biology and Translational Medicine [SISTM]
Bordeaux population health [BPH]
Statistics In System biology and Translational Medicine [SISTM]
Bordeaux population health [BPH]
WITTKOP, Linda
Statistics In System biology and Translational Medicine [SISTM]
Bordeaux population health [BPH]
Statistics In System biology and Translational Medicine [SISTM]
Bordeaux population health [BPH]
RICHERT, Laura
Statistics In System biology and Translational Medicine [SISTM]
Bordeaux population health [BPH]
Statistics In System biology and Translational Medicine [SISTM]
Bordeaux population health [BPH]
THIEBAUT, Rodolphe
Statistics In System biology and Translational Medicine [SISTM]
Bordeaux population health [BPH]
< Reduce
Statistics In System biology and Translational Medicine [SISTM]
Bordeaux population health [BPH]
Language
EN
Article de revue
This item was published in
Clinical Infectious Diseases. 2024-05-31p. ciae235
English Abstract
BACKGROUND: Analytical treatment interruption (ATI) is the gold standard in HIV research for assessing the capability of new therapeutic strategies to control viremia without antiretroviral treatment (ART). The viral ...Read more >
BACKGROUND: Analytical treatment interruption (ATI) is the gold standard in HIV research for assessing the capability of new therapeutic strategies to control viremia without antiretroviral treatment (ART). The viral setpoint is commonly used as endpoint to evaluate their efficacy. However, in line with recommendations from a consensus meeting, to minimize the risk of increased viremia without ART, trials often implement short ATI phases and stringent virological ART restart criteria. This approach can limit the accurate observation of the setpoint. METHODS: We analyzed viral dynamics in 235 people with HIV from 3 trials, examining virological criteria during ATI phases. Time-related (eg time to rebound, peak, and setpoint) and viral load magnitude-related criteria (peak, setpoint, and time-averaged AUC [nAUC]) were described. Spearman correlations were analyzed to identify (1) surrogate endpoints for setpoint and (2) optimal virological ART restart criteria mitigating the risks of ART interruption and the evaluation of viral control. RESULTS: Comparison of virological criteria between trials showed strong dependencies on ATI design. Similar correlations were found across trials, with nAUC the most strongly correlated with the setpoint, with correlations >0.70. A threshold >100 000 copies/mL for 2 consecutive measures is requested as a virological ART restart criterion. CONCLUSIONS: Our results are in line with recommendations and emphasize the benefits of an ATI phase >12 weeks, with regular monitoring, and a virological ART restart criterion of 10 000 copies/mL to limit the risk for patients while capturing enough information to keep nAUC as an optimal proxy to the setpoint.Read less <
English Keywords
HIV Cure
Analytical Treatment Interruption
Antiretroviral Treatment
Clinical Trials
Virological Endpoint
European Project
European HIV Vaccine Alliance (EHVA): a EU platform for the discovery and evaluation of novel prophylactic and therapeutic vaccine candidates
ANR Project
Initiative for the creation of a Vaccine Research Institute