Efavirenz-based Treatment Effects on CD4+ Cell Count Changes in People Living with HIV/AIDS: Assessing Heterogeneity and Publication Bias

Abstract

Background: Efavirenz (EFV)–based regimens have long been integral to antiretroviral therapy (ART). The extent to which EFV contributes to immunologic recovery remains clinically relevant, where EFV is still prescribed. Objective: To quantify CD4+ T-cell count change associated with EFV-based treatment and to assess heterogeneity and publication bias. Methods: We systematically searched PubMed, Scopus, Web of Science, Cochrane Library, and Google Scholar from 2000 to Aug 31, 2025, screened per PRISMA 2020, and included randomized or observational studies reporting baseline and follow-up CD4+ counts (or change/SD) for EFV-based arms. Random-effects meta- analysis summarized mean change; heterogeneity (Q, I²), leave-one-out sensitivity, and funnel plots/Egger’s test evaluated robustness and bias. Results: Five studies met criteria. The pooled mean CD4+ increase with EFV-based therapy was 184.5 cells/μL (95% CI 65.1–303.9), with I² = 0%. Sensitivity analyses did not materially alter estimates. Funnel-plot visual inspection showed no clear asymmetry, though power was limited (n = 5). Conclusions: EFV-based ART is associated with a clinically meaningful rise in CD4+ count—exceeding typical first-year gains observed after ART initiation— though precision is limited by the small evidence base. Findings should be interpreted alongside contemporary guidelines that prefer INSTI-based first-line regimens; nonetheless, results inform settings where EFV remains in use or is clinically indicated