Predictors of immunological non-response despite virological suppression in people living with HIV on antiretroviral therapy: A systematic review and meta-analysis.

Immunological Nonresponse (INR) in people living with HIV (PLWH) is characterized by inadequate CD4+ T-cell recovery despite effective viral suppression through antiretroviral therapy (ART). This systematic review and meta-analysis identify key clinical, demographic, and molecular predictors of INR to optimize immune recovery strategies. A comprehensive literature search was conducted in accordance with PRISMA 2020 guidelines, yielding 59 eligible studies, with a total of 19,511 individuals with INR. Study quality was assessed using the Newcastle-Ottawa Scale (NOS), and pooled effect estimates were calculated as odds ratio (OR), mean difference (MD), or standardized mean difference (SMD). Significant predictors of INR included male sex [OR 1.33 (1.12-1.58)], older age [MD 2.61 (1.42-3.81)], intravenous drug use [OR 1.67 (1.15-2.42)], hepatitis B coinfection [OR 1.30 (1.08-1.57)], hepatitis C coinfection [OR 1.85 (1.50-2.28)], tuberculosis [OR 1.77 (1.41-2.21)], advanced HIV stage [OR 2.66 (2.34-3.02)], and lower baseline and nadir CD4+ counts [SMD -3.82 (-4.94-(-2.70)), SMD -1.69 (-2.69-(-0.68))], respectively. Additionally, 57 biomarkers were identified as potential predictors of INR, implicating several immunological pathways. These findings underscore the multifactorial nature of INR and the need for personalized approaches among ART-treated individuals.