The effect of antiretroviral therapy with high central nervous system penetration on HIV-related cognitive impairment: a systematic review and meta-analysis

ABSTRACT

Chronic complications are a significant concern for people living with HIV/AIDS (PLWHA) infection. HIV-associated neurocognitive disorders (HAND) are prevalent in PLWHA. Yet, the efficacy of medications that penetrate the central nervous system (CNS) at preventing or slowing the progression of HAND remains largely unknown. The objective of this study was to determine whether high CNS penetration effectiveness (CPE) regimens improve neurocognitive test scores in PLWHA on combined antiretroviral therapy (cART). Primary literature evaluating cognitive outcomes based on CPE score of cART regimens in PLWHA was assembled from PubMed/Medline and EMBASE. Both randomized controlled trials and observational studies with at least 12 weeks of follow-up were included. A meta-analysis was conducted to calculate the standardized mean difference. Eight trials including a total of 3,303 patients with 13,103 person-years of follow-up were included in the systematic review. Four trials (n = 366 patients) met our inclusion criteria and were included in the meta-analysis. In the meta-analysis, HIV regimens with a high CPE score did not affect NPZ-4 or GDS scores (standardized mean difference (SMD) 0.10, 95% CI −0.19, 0.38; I²= 26%). Future studies with larger sample sizes are warranted to prospectively evaluate the relationship between CPE and progression of HAND.

KEYWORDS:

• HIV
• AIDS dementia complex
• HIV associated neurocognitive disease
• central nervous system penetration
• cognitive impairment

Acknowledgements

Contents of this study was presented as a poster at the ACCP Global Conference on Clinical Pharmacy from October 20-23, 2018 in Seattle, WA. Cross et al provided their data set for use in this analysis. We would like to thank all of the study participants, investigators, and data management teams of the included studies. Their study was funded by the South African Research Foundation, Medical Research Council of South Africa, Biological Psychiatry Special Interest Group of SASOP and the NIMH (R01 Grant MH085604).

Disclosure statement

No potential conflict of interest was reported by the author(s).

Institutional review board status

This study was deemed exempt by the Investigational Review Board at the University of Rhode Island.

Additional information

Funding

Buchanan was partially supported by the Avenir Award Program for Research on Substance Abuse and HIV/AIDS Award Number DP2DA046856 from National Institute on Drug Abuse of the National Institutes of Health. Buchanan and Vyas were partially supported by Institutional Development Award Number U54GM115677 from the National Institute of General Medical Sciences of the National Institutes of Health, which funds Advance Clinical and Translational Research (Advance-CTR). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.