Background
There is a global need to explore novel interventions conferring sustained HIV control without antiretroviral therapy (ART). The only current strategy to test efficacy is through an analytical treatment interruption (ATI). Inclusion of ‘placebo’ controls in future clinical trials poses ethical, logistical, and economic challenges and might be unnecessary if sufficient up-to-date data exists from non-intervention cohorts of people with HIV (PWH) who stop ART. To understand viral rebound dynamics and rates of post-treatment control (PTC) in the absence of any intervention, we undertook an individual-level participant data meta-analysis on time to viremia after ATI.
Methods
We included data from clinical studies with ≥5 separate available plasma HIV RNA viral load (pVL) measurements within the first 84 days post-ATI in PWH receiving either placebo or no intervention. Eligible prospective studies were identified through literature search on PubMed. Early-ART was defined as ART initiation within 6 months of HIV acquisition; others were classified as late-ART or unknown. Our data was used as reference to calculate the number of participants needed in either a single arm or 2-group randomized controlled trial design with a power of 90% to detect specified prolonged time to viremia or proportion of PTC at a 5% significant level, one-sided.
Results
In total, 24 studies with 382 individuals were included. 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% for early-ART and 1% for late-ART). If the expected outcome of an intervention is a frequency of 25% PTC among early-ART participants, 36 individuals would need to be included in a single arm design and 128 individuals in a 2-group randomized trial design.
Conclusions
Sustained control of pVL <50 copies/ml after 84 days off ART is rare in PWH who stop therapy, especially in those starting ART late. When designing future interventional HIV cure/remission trials, these findings help inform study size and design, potentially removing the need for a placebo arm thereby minimizing unnecessary risks to participants and their partners, while optimising resources.
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