Immune dysfunction drives adverse mpox outcomes among people living with human immunodeficiency virus: a systematic review and meta-analysis with CD4-based risk stratification.

BACKGROUND: People living with human immunodeficiency virus (HIV) accounted for a large share of cases during the 2022 multinational mpox outbreak, but whether adverse outcomes are attributable to HIV infection itself or to the degree of immune dysfunction remains uncertain. METHODS: We conducted a systematic review and meta-analysis according to PRISMA 2020 and Cochrane methods. PubMed, Embase, and Web of Science were searched from inception through January 31, 2026, with targeted literature updating through May 27, 2026. Observational studies reporting mpox outcomes stratified by HIV status were eligible. The primary outcome was hospitalization. Risk ratios (RRs) were pooled using DerSimonian-Laird random-effects models. RESULTS: Twenty studies were included in the qualitative synthesis and 13 studies comprising 32,685 participants were included in the hospitalization meta-analysis. HIV infection was associated with increased hospitalization risk (RR, 1.40; 95% CI, 1.07-1.85; I2 = 81%). The 95% prediction interval was wide (0.54-3.65), indicating that context, case mix, and hospitalization thresholds influenced observed effects. CD4-stratified evidence was not sufficiently uniform for a valid pooled CD4-specific effect estimate, but available studies consistently indicated that low CD4 count, uncontrolled HIV viremia, and disengagement from HIV care identify the subgroup at greatest risk for hospitalization, severe disease, prolonged infection, and death. CONCLUSION: Adverse mpox outcomes among people living with HIV are better explained by immune status and HIV disease control than by HIV serostatus alone. CD4-based risk stratification provides a clinically actionable framework for triage, follow-up intensity, antiviral-treatment consideration, and integration of mpox management with HIV care.