HIV DNA and Dementia in Treatment-Naïve HIV-1-Infected Individuals in Bangkok, Thailand

Abstract

High HIV-1 DNA (HIV DNA) levels in peripheral blood mononuclear cells (PBMC) correlate with HIV-1-associated dementia (HAD) in patients on highly active antiretroviral therapy (HAART). If this relationship also exists among HAART-naïve patients, then HIV DNA may be implicated in the pathogenesis of HAD. In this study, we evaluated the relationship between HIV DNA and cognition in subjects naïve to HAART in a neuro AIDS cohort in Bangkok, Thailand. Subjects with and without HAD were recruited and matched for age, gender, education, and CD4 cell count. PBMC and cellular subsets were analyzed for HIV DNA using real-time PCR. The median log10 HIV DNA copies per 106 PBMC for subjects with HAD (n=15) was 4.27, which was higher than that found in subjects without dementia (ND; n=15), 2.28, p<0.001. This finding was unchanged in a multivariate model adjusting for plasma HIV-1 RNA levels. From a small subset of individuals, in which adequate number of cells were available, more HIV DNA was in monocytes/macrophages from those with HAD compared to those with ND. These results are consistent with a previous report among HAART-experienced subjects, thus further implicating HIV DNA in the pathogenesis of HAD.

Vascular risk factors, HIV serostatus, and cognitive dysfunction in gay and bisexual men

“…Perhaps there are other HIV-associated factors not assessed in this study that are better markers of cognitive dysfunction than CD4 ϩ cell counts and HIV RNA levels. For example, the level of proviral HIV DNA in peripheral blood mononuclear cells may have a stronger association with HIV-associated dementia 18 and performance on individual neuropsychological tests 19 than either CD4 ϩ cell counts or viral load in plasma. Chronological age is often entered as a covariate in the analysis of neuropsychological test data.…”

HIV DNA in CD14+ reservoirs is associated with regional brain atrophy in patients naive to combination antiretroviral therapy

“…[16] Due to feasibility issues, subjects were screened for levels of PBMC HIV DNA rather than CD14+ HIV DNA, since this required less real-time work at screening and because PBMC HIV DNA had correlated strongly to CD14+ HIV DNA in previous studies. [14, 17] Based on the distribution of our preliminary data, and using a double-blind study design with all clinical staff blinded to HIV DNA levels and laboratory technicians to clinical data, our goal was to enroll 30 cases with more than and 30 cases with fewer than 1000 copies of HIV DNA per 10 6 PBMCs. We further stratified each HIV DNA group by age (greater or less than 35 years) to minimize clustering by age within HIV DNA strata, which could impact cognition.…”

Peripheral blood HIV DNA is associated with atrophy of cerebellar and subcortical gray matter

“…HIV DNA in peripheral blood mononuclear cells (PBMCs) constitutes a viral reservoir that may contribute to ongoing neurologic impairment. Detectable PBMC HIV DNA is associated with cognitive dysfunction in cART-naïve individuals 4 and in cART-treated subjects with undetectable plasma HIV RNA. 5,6 HIV DNA within the activated CD141 monocyte subset of PBMC correlates with neurocognitive decline.…”