Antiretroviral Therapy Intensification for Neurocognitive Impairment in Human Immunodeficiency Virus

被引：21

作者：

Letendre, Scott L. ^{[1
]}

Chen, Huichao ^{[2
]}

McKhann, Ashley ^{[2
]}

Roa, Jhoanna ^{[3
]}

Vecchio, Alyssa ^{[4
]}

Daar, Eric S. ^{[5
]}

Berzins, Baiba ^{[6
]}

Hunt, Peter W. ^{[7
]}

Marra, Christina M. ^{[8
]}

Campbell, Thomas B. ^{[9
]}

Coombs, Robert W.

Ma, Qing ^{[10
]}

Swaminathan, Shobha ^{[11
]}

Macatangay, Bernard J. C. ^{[12
]}

Morse, Gene D.

Miller, Thomas

Rusin, David

Greninger, Alexander L. ^{[8
]}

Ha, Belinda ^{[13
]}

Alston-Smith, Beverly ^{[14
]}

Robertson, Kevin ^{[4
]}

Paul, Robert ^{[15
]}

Spudich, Serena ^{[16
]}

机构：

[1] Univ Calif San Diego, San Diego, CA USA

[2] Harvard TH Chan Sch Publ Hlth, Boston, MA USA

[3] DLH Corp, Silver Spring, MD USA

[4] Univ N Carolina, Chapel Hill, NC USA

[5] Univ Calif Los Angeles, Lundquist Inst Harbor, Med Ctr, Torrance, CA USA

[6] Northwestern Univ, Chicago, IL USA

[7] Univ Calif San Francisco, San Francisco, CA USA

[8] Univ Washington, Sch Med, Seattle, WA USA

[9] Univ Colorado, Sch Med, Denver, CO USA

[10] SUNY Buffalo, Buffalo, NY USA

[11] Rutgers New Jersey Med Sch, Newark, NJ USA

[12] Univ Pittsburgh, Pittsburgh, PA USA

[13] ViiV Healthcare Ltd, Res Triangle Pk, NC USA

[14] NIH, Div AIDS, Rockville, MD USA

[15] Univ Missouri, St Louis, MO USA

[16] Yale Sch Med, New Haven, CT USA

来源：

CLINICAL INFECTIOUS DISEASES | 2023年 / 77卷 / 06期

关键词：

HIV; cognition; brain; antiretroviral therapy; CENTRAL-NERVOUS-SYSTEM; HIV-INFECTED PATIENTS; CEREBROSPINAL-FLUID; PENETRATION-EFFECTIVENESS; NEUROPSYCHOLOGICAL IMPAIRMENT; IMMUNE ACTIVATION; ADVERSE EVENTS; MARAVIROC; DOLUTEGRAVIR; PERFORMANCE;

D O I：

10.1093/cid/ciad265

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

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/mu L. 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/m(2), 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.

引用

页码：866 / 874

页数：9