Antiretroviral therapy improves neurocognitive impairment in people living with HIV? A meta-analysis

Despite the widespread use of effective antiretroviral therapy (ART), HIV-associated neurocognitive disorder (HAND) remains a prevalent complication, affecting quality of life and mortality. While ART is known to suppress viral replication and restore immune function, its direct impact on neurocognitive impairment (NCI) has remained a subject of controversy. This meta-analysis aimed to clarify whether ART improves cognitive function in people living with HIV (PLWH) by synthesizing data from both cross-sectional and cohort studies.

The authors conducted a systematic review and meta-analysis of 16 studies (14 cross-sectional and 2 cohort studies) published up to April 2019, involving 6,694 participants. The researchers compared cognitive outcomes between PLWH receiving ART and those who were ART-naïve. They also performed subgroup analyses based on age and clinical status to determine if specific populations derived greater cognitive benefit from treatment.

The study revealed a clear divergence in results based on research design. Cross-sectional studies generally failed to show that ART-treated individuals performed better than those not on treatment. In contrast, longitudinal cohort studies demonstrated significant cognitive improvement within three to six months of initiating ART. Further analysis suggested that these benefits are most pronounced in PLWH who have advanced HIV infection, poor physical condition, and compromised immune status at baseline. For the broader population of PLWH, particularly those with higher CD4 counts or better health, the cognitive benefits of ART were less clear.

These findings suggest that while ART is essential for managing HIV, it is not a universal cure for neurocognitive impairment. The results highlight that the most significant cognitive gains from ART occur in patients with severe disease, likely due to the reduction of HIV viremia and the recovery of cerebral health. This underscores the importance of early diagnosis and treatment, while also signaling that clinicians should look for other factors—such as comorbidities and aging—when managing cognitive issues in stable, long-term HIV patients.