Improved neuropsychological and neurological functioning across three antiretroviral regimens in diverse resource-limited settings: AIDS Clinical Trials Group study a5199, the International Neurological Study.

TitleImproved neuropsychological and neurological functioning across three antiretroviral regimens in diverse resource-limited settings: AIDS Clinical Trials Group study a5199, the International Neurological Study.
Publication TypeJournal Article
Year of Publication2012
AuthorsRobertson K, Jiang H, Kumwenda J, Supparatpinyo K, Evans S, Campbell TB, Price R, Tripathy S, Kumarasamy N, La Rosa A, Santos B, Silva MT, Montano S, Kanyama C, Faesen S, Murphy R, Hall C, Marra CM, Marcus C, Berzins B, Allen R, Housseinipour M, Amod F, Sanne I, Hakim J, Walawander A, Nair A
Corporate Authors5199 study team, AIDS Clinical Trials Group
JournalClin Infect Dis
Volume55
Issue6
Pagination868-76
Date Published2012 Sep
ISSN1537-6591
KeywordsAcquired Immunodeficiency Syndrome, Adult, AIDS Dementia Complex, Anti-Retroviral Agents, Antiretroviral Therapy, Highly Active, Female, HIV-1, Humans, Male, Neurologic Examination, Psychological Tests, Treatment Outcome
Abstract

BACKGROUND: AIDS Clinical Trials Group (ACTG) A5199 compared the neurological and neuropsychological (NP) effects of 3 antiretroviral regimens in participants infected with human immunodeficiency virus type 1 (HIV-1) in resource-limited settings.

METHODS: Participants from Brazil, India, Malawi, Peru, South Africa, Thailand, and Zimbabwe were randomized to 3 antiretroviral treatment arms: A (lamivudine-zidovudine plus efavirenz, n = 289), B (atazanavir, emtricitabine, and didanosine-EC, n = 293), and C (emtricitabine-tenofovir-disoproxil fumarate plus efavirenz, n = 278) as part of the ACTG PEARLS study (A5175). Standardized neurological and neuropsychological (NP) screening examinations (grooved pegboard, timed gait, semantic verbal fluency, and finger tapping) were administered every 24 weeks from February 2006 to May 2010. Associations with neurological and neuropsychological function were estimated from linear and logistic regression models using generalized estimating equations.

RESULTS: The median weeks on study was 168 (Q1 = 96, Q3 = 192) for the 860 participants. NP test scores improved (P < .05) with the exception of semantic verbal fluency. No differences in neurological and neuropsychological functioning between treatment regimens were detected (P > .10). Significant country effects were noted on all NP tests and neurological outcomes (P < .01).

CONCLUSIONS: The study detected no significant differences in neuropsychological and neurological outcomes between randomized ART regimens. Significant improvement occurred in neurocognitive and neurological functioning over time after initiation of ARTs. The etiology of these improvements is likely multifactorial, reflecting reduced central nervous system HIV infection, better general health, and practice effects. This study suggests that treatment with either of the World Health Organization -recommended first-line antiretroviral regimens in resource-limited settings will improve neuropsychological functioning and reduce neurological dysfunction.

CLINICAL TRIALS REGISTRATION: NCT00096824.

DOI10.1093/cid/cis507
Alternate JournalClin. Infect. Dis.
PubMed ID22661489
PubMed Central IDPMC3491853
Grant List5 U01AI069401 / AI / NIAID NIH HHS / United States
5U01 AI069438-03 / AI / NIAID NIH HHS / United States
5U01AI069417-03 / AI / NIAID NIH HHS / United States
5U01AI069426-03 / AI / NIAID NIH HHS / United States
AI-068634 / AI / NIAID NIH HHS / United States
AI069399 / AI / NIAID NIH HHS / United States
AI069432 / AI / NIAID NIH HHS / United States
AI069450 / AI / NIAID NIH HHS / United States
AI069518 / AI / NIAID NIH HHS / United States
AI69476 / AI / NIAID NIH HHS / United States
P30 AI050410 / AI / NIAID NIH HHS / United States
U01A1069518 / / PHS HHS / United States
U01AI068636 / AI / NIAID NIH HHS / United States