CD4 Count and Clinical Outcomes of Mpox in People Living With HIV: A Systematic Review and Meta-Analysis

HIV causes immunosuppression by targeting CD4+ T lymphocytes, which may influence susceptibility and clinical outcomes of coinfections such as the Mpox virus (MPXV). Despite conflicting evidence, understanding the relationship between CD4 counts and MPXV severity in people living with HIV (PLWH) remains critical. This study systematically reviews and meta-analyzes available evidence to elucidate this association.

Following PRISMA guidelines, a comprehensive search from a variety of databases was conducted for studies published between January 2014 and August 2025. Inclusion criteria encompassed observational studies reporting on HIV and MPXV co-infection with data on CD4 counts and clinical outcomes. Six studies, including 1254 participants, were included. Data extraction focused on immune parameters, disease severity, and clinical manifestations. The Newcastle-Ottawa Scale assessed study quality, and meta-analyses evaluated pooled associations, heterogeneity, and publication bias.

Meta-analysis revealed no statistically significant association between CD4 counts and MPXV disease severity (p = 0.1072). The pooled mean CD4 count was 692.38 cells/mm³ (95% CI: 647.73 to 737.03). Most HIV-positive patients, particularly those on ART, experienced mild disease courses with favorable outcomes, with no mortality reported. Although there was a trend indicating that lower CD4 counts (< 200 or 500 cells/mm³) might be associated with increased complications, these differences were not statistically significant.

CD4 count alone was not found to be a statistically significant factor associated with MPXV severity among HIV-coinfected individuals on ART. Effective viral suppression and immune reconstitution through ART appear protective, emphasizing the need to prioritize ART adherence over reliance on CD4 metrics and validation in well-designed prospective studies.