Antiretroviral Therapy Intensification for Neurocognitive Impairment in Human Immunodeficiency Virus

Year: 2023

Type: article

Abstract: BACKGROUND: Neurocognitive impairment (NCI) in people with HIV (PWH) on antiretroviral therapy (ART) is common and may result from persistent HIV replication in the central nervous system. METHODS: A5324 was a randomized, double-blind, placebo-controlled, 96-week trial of ART intensification with dolutegravir (DTG) + MVC, DTG + Placebo, or Dual - Placebo in PWH with plasma HIV RNA <50 copies/mL on ART and NCI. The primary outcome was the change on the normalized total z score (ie, the mean of individual NC test z scores) at week 48. RESULTS: Of 357 screened, 191 enrolled: 71% male, 51% Black race, 22% Hispanic ethnicity; mean age 52 years; mean CD4+ T-cells 681 cells/µL. Most (65%) had symptomatic HIV-associated NC disorder. Study drug was discontinued due to an adverse event in 15 (8%) and did not differ between arms (P = .17). Total z score, depressive symptoms, and daily functioning improved over time in all arms with no significant differences between them at week 48 or later. Adjusting for age, sex, race, study site, efavirenz use, or baseline z score did not alter the results. Body mass index modestly increased over 96 weeks (mean increase 0.32 kg/m2, P = .006) and did not differ between arms (P > .10). CONCLUSIONS: This is the largest, randomized, placebo-controlled trial of ART intensification for NCI in PWH. The findings do not support empiric ART intensification as a treatment for NCI in PWH on suppressive ART. They also do not support that DTG adversely affects cognition, mood, or weight.

Source: Clinical Infectious Diseases

DOI: 10.1093/cid/ciad265

Institutions: University of California San Diego, Harvard University, DLH Corporation (United States), University of North Carolina at Chapel Hill, University of California, Los Angeles, The Lundquist Institute, Los Angeles Medical Center, Northwestern University, University of California, San Francisco, University of Washington, University of Colorado Anschutz, University of Colorado Denver, University at Buffalo, State University of New York, Rutgers New Jersey Medical School, University of Pittsburgh, National Institutes of Health, Office of AIDS Research, University of Missouri–St. Louis, Yale University

Language: English

Topic: HIV Research and Treatment

Subfield: Virology

Field: Immunology and Microbiology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: bronze

Funders: Gilead Sciences, AIDS Clinical Trials Group, University of Rochester, ViiV Healthcare, ACT Government, National Institutes of Health, National Institute on Aging, National Institute of Mental Health, National Institute on Drug Abuse, National Institute of Allergy and Infectious Diseases, National Institute of Neurological Disorders and Stroke, National Center for Advancing Translational Sciences

OpenAlex ID: W4376616719