Improved neuropsychological and neurological functioning across three antiretroviral regimens in diverse resource-limited settings: Aids clinical trials group study A5199, the international neurological study

K. Robertson*, H. Jiang, J. Kumwenda, K. Supparatpinyo, S. Evans, T. B. Campbell, R. Price, S. Tripathy, N. Kumarasamy, A. La Rosa, B. Santos, M. T. Silva, S. Montano, C. Kanyama, S. Faesen, R. Murphy, C. Hall, C. M. Marra, C. Marcus, B. BerzinsR. Allen, M. Housseinipour, F. Amod, I. Sanne, J. Hakim, A. Walawander, A. Nair

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

38 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)868-876
Number of pages9
JournalClinical Infectious Diseases
Volume55
Issue number6
DOIs
StatePublished - Sep 2012

ASJC Scopus subject areas

  • Microbiology (medical)
  • Infectious Diseases

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