The rate of new human immunodeficiency virus (HIV) infections globally is alarming. Although antiretroviral therapy (ART) improves the quality of life among this group of patients, ARTs are associated with risk of cardiovascular diseases (CVD). Moreover, virally suppressed patients still experience immune activation associated with HIV migration from reservoir sites. Statins are widely recommended as therapeutic agents to control ART-related CVD; however, their impacts on the cluster of differentiation (CD)4 count and viral load are inconsistent. To assess the effect of statins on markers of HIV infections, immune activation and cholesterol, we thoroughly reviewed evidence from randomised controlled trials. We found 20 relevant trials from three databases with 1802 people living with HIV (PLHIV) on statin–placebo treatment. Our evidence showed no significant effect on CD4 T-cell count standardised mean difference (SMD): (−0.59, 95% confidence intervals (CI): (−1.38, 0.19),p= 0.14) following statin intervention in PLHIV on ART. We also found no significant difference in baseline CD4 T-cell count (SD: (−0.01, 95%CI: (−0.25, 0.23),p= 0.95). Our findings revealed no significant association between statins and risk of viral rebound in PLHIV with undetectable viral load risk ratio (RR): (1.01, 95% CI: (0.98, 1.04),p= 0.65). Additionally, we found a significant increase in CD8+CD38+HLA-DR+T-cells (SMD (1.10, 95% CI: (0.93, 1.28),p< 0.00001) and CD4+CD38+HLA-DR+T-cells (SMD (0.92, 95% CI: (0.32, 1.52),p= 0.003). Finally, compared to placebo, statins significantly reduced total cholesterol (SMD: (−2.87, 95% CI: (−4.08, −1.65),p< 0.0001)). Our results suggest that the statin lipid-lowering effect in PLHIV on ART may elevate immune activation without influencing the viral load and CD4 count. However, due to the limited evidence synthesised in this meta-analysis, we recommend that future powered trials with sufficient sample sizes evaluate statins’ effect on CD4 count and viral load, especially in virally suppressed patients.