Safety of Bacillus Calmette-Guérin Vaccination and Impact on HIV-1 Latent Reservoir Size in People With Treated HIV-1 Infection.

Background: Bacillus Calmette-Guérin (BCG) vaccination, used against tuberculosis, is recognized for its immunomodulatory properties, a phenomenon referred to as "trained immunity." Given these effects, there is increasing interest in evaluating its safety and impact on immune function in people living with HIV-1 (PWH). Historically, BCG was contraindicated in PWH due to safety concerns in immunocompromised individuals. This study aims to assess both the safety of BCG in PWH and its effects on the HIV-1 latent reservoir size. Methods: This Phase IIA randomized, double-blind, placebo-controlled, single-center trial enrolled 60 PWH with a suppressed viral load and CD4 T-cell count >350/μL. Participants were randomized in a stepped-wedge design into equal groups for early or late BCG vaccination. Each participant received a single intradermal dose of BCG vaccine followed by a placebo 3 months later, or vice versa. The HIV-1 latent reservoir was quantified at 3-month intervals to day 270. The primary endpoint was the HIV-1 reservoir size 6 months postvaccination, with secondary endpoints including safety outcomes. Results: No significant differences were found in intact proviral HIV-1 DNA levels at 6 months compared to baseline. Local reactions occurred in 96% of participants, leading to scarring in 73%. No systemic infections or serious BCG-related adverse events were observed. Conclusions: BCG vaccination is safe in PWH, but local skin reactions including scarring are common. There was no significant effect on the HIV-1 reservoir. These findings provide valuable insights into the safety profile of BCG vaccination in PWH, emphasizing its potential for broader immunological studies.