Safety of the M72/AS01 Tuberculosis Vaccine in People Living With HIV: A Systematic Review and Meta-Analysis

Abstract

Abstract Background Tuberculosis (TB) remains a leading cause of morbidity and mortality among people living with HIV (PLHIV). Although M72/AS01 demonstrated efficacy against active TB in HIV-negative adults, its safety in PLHIV is uncertain. As AS01 induces strong innate immune activation, evaluating tolerability in immunocompromised individuals is essential. We assessed the safety of M72/AS01 in PLHIV receiving antiretroviral therapy (ART). Methods We systematically searched MEDLINE, Embase, CENTRAL, and Web of Science for randomized controlled trials (RCTs) of PLHIV receiving M72/AS01 or placebo (last search 28 September 2025). Risk of bias was assessed using RoB 2 and certainty of evidence with GRADE. The protocol was registered in PROSPERO (CRD420251180412). Primary outcomes were risks of solicited local and systemic adverse events (AEs), any grade and grade 3, within 7 days postvaccination. Pooled risk ratios (RRs) were estimated using random-effects inverse-variance models. Results Three RCTs (510 participants; M72/AS01 = 263, placebo = 247) were included. M72/AS01 increased risk of pain (RR 3.24, 95% CI 1.87–5.62), swelling (RR 4.64, 95% CI 2.93–7.34), headache (RR 1.83, 95% CI 1.52–2.20), myalgia (RR 2.36, 95% CI 1.80–3.10), and fever (RR 1.95, 95% CI 1.45–2.63). Events were predominantly mild-to-moderate and self-limited. No meaningful difference was observed in unsolicited AEs, and no vaccine-related serious AEs (SAEs) were reported. Certainty ranged from high (common events) to low (rare grade 3 AEs) due to imprecision. Conclusions M72/AS01 demonstrated a favorable safety profile in immunologically stable, virologically suppressed adults living with HIV on ART, with no increase in SAE or unsolicited AEs. These findings support its safe use and justify future studies evaluating its efficacy for TB prevention in this population.