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HIV DNA Correlates with HIV-1-associated Dementia in ART-naive Patients
Bruce Shiramizu*1, S Nidhinandana2, P Sithinamsuwan2, W Apateerapong1, S Ratto-Kim1,3, G Watt1, K Robertson4, R Paul5, C Shikuma1, V Valcour1, and South East Asia Research Collaboration with Hawaii (SEARCH)
1Univ of Hawaii, John A Burns Sch of Med, Honolulu, US; 2Phramongkutklao Med Ctr, Bangkok, Thailand; 3Armed Forces Res Inst of the Med Sci, Bangkok, Thailand; 4Univ of North Carolina at Chapel Hill, US; and 5Brown Med Sch, Miriam Hosp, Providence, RI, US
Background: Increase in HIV-1 proviral DNA (HIV DNA) is strongly
associated (OR = 2.83, 1.57 to 5.08) with a diagnosis of HIV-1-associated
dementia (HAD) vs normal cognition among patients heavily treated with ART.
There is extensive controversy as to whether the HAD currently seen in
populations with ready-access to ART are similar to that seen in the era prior
to the availability of potent ART, and no data are available on whether an
association of HIV DNA and HAD would be seen in ART-naïve individuals presenting
with HAD. A unique opportunity exists to study the phenomena among ART-naive HIV-1-infected
patients with and without HAD in Thailand prior to initiation of
treatment. The goal of the study was to determine if baseline HIV DNA is
associated and a marker for HAD in ART-naïve subjects.
Methods: Following
informed-consent, subjects enrolled in the SEARCH Cohort as per guidelines
established by local IRB. From the cohort, patients with HAD (n = 12), HIV-1-infected non-HAD patients
(n = 12), matched for age, gender,
education, and CD4 cell count; and matched HIV-1-seronegative controls (n = 12) for comparison had peripheral
blood mononuclear cells obtained and analyzed for HIV DNA at entry. HIV DNA was
assessed by real-time polymerase chain reaction. Diagnosis of dementia was
based on AAN 1991 criteria. The Student’s t-test
was used to analyze the HIV-1-infected groups.
Results: HIV DNA was significantly
higher in HAD (n = 12, mean 2.20 [0.25])
vs non-HAD (n = 12, mean 0.73 [0.39]),
calculated as log10 HIV DNA copy/106 cells, p = 0.024. No HIV DNA was found in seronegative
controls (n = 12). Mean baseline HIV-1
RNA levels (copies/mL):CD4 cell counts (cells/mL)
from HAD and non-HAD subjects were 274,000 (range 23,000 to 750,000):73 (range 3
to 318) and 288,000 (range 892,000 to 750,000):61 (range 8 to 222),
respectively, showing no difference.
 
Conclusions: High HIV DNA is a marker of HAD, not only in
subjects on potent ART, as previously reported but also in ART-naïve subjects. Subjects
enrolled in the SEARCH Cohort, diagnosed with HAD at baseline, showed a
significant elevation in HIV DNA compared to individuals without HAD. This
suggests that high HIV DNA may be a novel marker suggesting a potential role in
the pathogenesis of HAD.
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