Antiretroviral Therapy Intensification for Neurocognitive Impairment in HIV

• Published in: Clinical infectious diseases
• Main Authors: Letendre, Scott L, Chen, Huichao, McKhann, Ashley, Roa, Jhoanna, Vecchio, Alyssa, Daar, Eric S, Berzins, Baiba, Hunt, Peter W, Marra, Christina M, Campbell, Thomas B, Coombs, Robert W, Ma, Qing, Swaminathan, Shobha, Macatangay, Bernard J C, Morse, Gene D, Miller, Thomas, Rusin, David, Greninger, Alexander L, Ha, Belinda, Alston-Smith, Beverly, Robertson, Kevin, Paul, Robert, Spudich, Serena
• Format: Journal Article
• Language: English
• Published: 15.05.2023
• ISSN: 1537-6591; 1537-6591
• DOI: 10.1093/cid/ciad265

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.BACKGROUNDNeurocognitive 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.A5324 was a randomized, double-blind, placebo-controlled 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. Assessments were repeated at 24, 48, 72, and 96 weeks. The primary outcome was the change from baseline to week 48 on the normalized total z-score (i.e., the mean of the individual NC test z-scores).METHODSA5324 was a randomized, double-blind, placebo-controlled 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. Assessments were repeated at 24, 48, 72, and 96 weeks. The primary outcome was the change from baseline to week 48 on the normalized total z-score (i.e., the mean of the individual NC test z-scores).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=0.19). 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=0.006) and did not differ between arms (p>0.10).RESULTSOf 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=0.19). 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=0.006) and did not differ between arms (p>0.10).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.CONCLUSIONSThis 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.