Time to HIV viral rebound and frequency of post-treatment control after analytical interruption of antiretroviral therapy: an individual data-based meta-analysis of 24 prospective studies
Jesper Damsgaard Gunst, Jesal Gohil, Jonathan Z. Li, Ronald J. Bosch, Caitlin White, Tae‐Wook Chun, Beatriz Mothe, Kathleen Gittens, Lauren Praiss, Marie‐Angélique De Scheerder, Linos Vandekerckhove, Kevin Escandón-Vargas, Ann Thorkelson, Timothy W. Schacker, Devi SenGupta, Christian Brander, Emmanouil Papasavvas, Luis J. Montaner, Javier Martínez‐Picado, Ruxandra Câlin, Antonella Castagna, Camilla Muccini, Wesley de Jong, Lorna Leal, Felipe García, Rob A. Gruters, Timothy Tipoe, John Frater, Ole S. Søgaard, Sarah Fidler
Abstract
The only current strategy to test efficacy of novel interventions for sustained HIV control without antiretroviral therapy (ART) among people with HIV (PWH) is through an analytical treatment interruption (ATI). Inclusion of ‘placebo’ controls in ATIs poses ethical, logistical, and economic challenges. To understand viral dynamics and rates of post-treatment control (PTC) after ATI among PWH receiving either placebo or no intervention, we undertook an individual-participant data meta-analysis. In total, 24 eligible prospective studies with 382 individuals with ≥5 plasma HIV RNA viral loads (pVLs) within the first 84 days post-ATI were included. Early-ART was defined as ART initiation within 6 months of HIV acquisition; others were classified as late-ART or unknown. Median age was 42 years, 91% male, 75% white, 45% received early-ART. Median time to pVL >50, >400, and >10,000 copies/mL was 16 days (interquartile range [IQR]:13–25), 21 (IQR:15–28), and 32 (IQR:20–35), respectively. PTC defined as pVL <50 copies/mL at day 84 occurred in 4% (n = 14) of participants (6% early-ART and 1% late-ART). Sustained PTC of pVL <50 copies/ml after 84 days is rare in PWH, especially in those starting ART late. Our findings inform future interventional HIV cure/remission trials on study size and design. Clinical trials testing efficacy of novel HIV treatments rely on analytical treatment interruption (ATI). Using data from 24 prospective studies, the authors here show that the virus becomes detectable after around 16 days of ATI and that only 4% of individuals have sustained control of HIV, providing information for future clinical trial design.