The Effect of Successful Antiretroviral Therapy on Immune Activation and Reconstitution in HIV Infected Adults: A Systematic Review and Meta-Analysis.

We performed a systematic review and meta-analysis to investigate the impact of antiretroviral therapy (ART) on immune activation and reconstitution in people living with human immunodeficiency virus (PLWH). The PubMed electronic database and gray literature were searched from inception until March 2020. Studies were included if they reported the levels of immune activation and reconstitution at baseline and post-treatment. The random-effect model was used to calculate effect sizes. We included a total of ten studies comprising of 1 553 PLWH with an average age of 38.02 ± 10.10 years and a male/female ratio of 3.76. Pooled estimates showed a modest increase in the level of immune activation post-treatment (SMD: 0.64 [95% CI: -1.34, 2.63]; I2 = 98%, pH < 0.00001). In addition, treatment with ART significantly reconstituted the immune system (SMD: 0.70 [95% CI: 0.27, 1.44]; I2 = 68%, pH = 0.009). Notably, the level of immune reconstitution was independent of viral load or the treatment duration but dependent on the class of ARV drugs. Consequently, protease inhibitors were associated with the highest degree of immune restoration, followed by chemokine antagonists and lastly integrase inhibitors. In conclusion, immune activation persists in PLWH despite viral suppression and the degree of immune reconstitution is dependent on the drug class. Therefore, inclusion of protease inhibitors in ART may be of great benefit in immune restoration in patients with very low CD4 count.