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


BACKGROUND
NCT00096824.
University of North Carolina, Chapel Hill, 27599-7025, USA. kevinr@neurology.unc.edu
K
K
Robertson
H
H
Jiang
J
J
Kumwenda
K
K
Supparatpinyo
S
S
Evans
T B
TB
Campbell
R
R
Price
S
S
Tripathy
N
N
Kumarasamy
A
A
La Rosa
B
B
Santos
M T
MT
Silva
S
S
Montano
C
C
Kanyama
S
S
Faesen
R
R
Murphy
C
C
Hall
C M
CM
Marra
C
C
Marcus
B
B
Berzins
R
R
Allen
M
M
Housseinipour
F
F
Amod
I
I
Sanne
J
J
Hakim
A
A
Walawander
A
A
Nair
D015526:AIDS Dementia Complex / Q000453:epidemiology* / Q000517:prevention & control*; D000163:Acquired Immunodeficiency Syndrome / Q000150:complications* / Q000188:drug therapy* / Q000821:virology; D000328:Adult; D044966:Anti-Retroviral Agents / Q000627:therapeutic use*; D023241:Antiretroviral Therapy, Highly Active / Q000379:methods*; D005260:Female; D015497:HIV-1 / Q000472:pathogenicity; D006801:Humans; D008297:Male; D009460:Neurologic Examination; D011581:Psychological Tests; D016896:Treatment Outcome
D044966:Anti-Retroviral Agents