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Intermediate (12 Months) and Long-term (6 Years) Cognitive Response to HAART in 2 Thai Cohorts
V Valcour1,2,3, P Sithinamsuwan4, W Pumpradit5, J Ananworanich1,3, S Nidhinandana4, W Apateerapong3, K Robertson6, R Paul7, U Siangphoe3, Cecilia Shikuma*1,3, and Southeast Asia Res Collaboration with Hawaii (SEARCH) 001 Protocol Team
1Hawaii AIDS Clinical Res Prgm, Univ of Hawaii, Honolulu, US; 2Univ of California, San Francisco, US; 3South East Asia Res Collaboration with Univ of Hawaii, Bangkok, Thailand; 4Phramongkutklao Hosp, Bangkok, Thailand; 5HIV Netherlands Australia Thailand Res Collaboration, Bangkok; 6Univ of North Carolina at Chapel Hill, US; and 7Univ of Missouri, St Louis, US
Background: Few data are available regarding
HIV-associated cognitive impairment in non-clade B virus after successful HAART.
These 2 studies were designed to define the 12-month cognitive, immunological,
and virological response to HAART (SEARCH 001) and the frequency of cognitive
disorders in a well-characterized plasma HIV RNA undetectable 2NN Cohort (SEARCH
005) from Bangkok, Thailand.
Methods: SEARCH 001 enrolled 15 HIV-1-associated
dementia (HAD) and 15 non-HAD patients who underwent careful longitudinal
neuropsychological characterization at 0, 6, and 12 months following NNRTI-based
HAART. SEARCH 005 was a cross-sectional evaluation approximately 6 years after
first initiation of HAART among patients only treated with NNRTI and all with long-term
undetectable plasma HIV RNA levels. All participants completed the World Health
Organization/National Institute of Mental Health international HIV neuropsychological
battery and compared to 170 HIV– Thai controls. All SEARCH 001
participants were hepatitis C negative, free of drug use, and confirmed to be
infected with CRF 01_AE HIV.
Results: Among the 19 SEARCH 001 participants with
undetectable plasma HIV RNA at both 6 and12 months, the mean (range) global
deficit score (GDS) improved in both HAD and non-HAD groups, but remained
inferior to that of controls at 12 months among HAD patients (see the figure).
Among 22 participants in SEARCH 005, 8 had mild impairment on
neuropsychological testing (4 of 22 with asymptomatic neurocognitive impairment,
and 4 of 22 with minor neurocognitive disorder). Median CD4 (IQR) was 429 (312 to
588) cells/mm3 and did not differ by impairment group. The mean
global deficit score (range) was 0.51 (0.11 to 1.05) for impaired and 0.20 (0
to 1.00) for unimpaired individuals (p = 0.048). Greatest impairment was
seen in the digit symbol test (p = 0.038) and the grooved pegboard test
(p = 0.026 for dominant and p = 0.079 for non-dominant hand).
Conclusions: Dementia patients in SEARCH 001 have a
robust but incomplete cognitive response to HAART at 12 months despite at least
6 months of undetectable plasma HIV RNA levels. In SEARCH 005, cognitive
impairment can be identified in about a third of participants at 6 years
despite successful HAART. These findings have implications for cognitive
limitations of HAART in CRF 01_AE HIV virus.
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