Background:  We previously reported an association between high HIV DNA and diagnosis of HIV-1-associated dementia (HAD) vs normal cognition; as well as a parallel association with deficits in neuropsychological function. To determine the spectrum of neurocognitive disorders influenced by HIV DNA, specimens not previously analyzed were obtained from the Hawaii Aging with HIV Cohort (HAHC) and assessed for HIV DNA.

Methods:  Peripheral blood mononuclear cells (PBMC) were obtained from HAHC participants, who previously had consented to have specimens stored for this study. Exclusion criteria included: current substance abuse or history of central nervous system (CNS) transient ischemic attack or stroke. Subjects underwent a battery of neuropsychological tests to assess cognitive domains; and a consensus conference was held to establish a neurocognitive diagnosis according to American Academy of Neurology 1991 criteria. HIV DNA was measured by real-time polymerase chain reaction (RT-PCR). A univariate logistic regression model was used with a generalized logits link function for the analyses.

Results:  PBMC from 189 HIV-infected subjects were available (83 normal cognition; 85 minor cognitive-motor disorder; 21 HAD). Neuropsychological deficits representing neurocognitive domains were significantly associated with baseline HIV DNA, adjusted for age, ethnicity, CD4 cell count, and premorbid IQ. Moreover, the univariate logistic regression model showed a strong probability of HIV DNA levels across a continuum of cognitive diagnosis (normal cognition; minor cognitive motor disorder, minor cognitive-motor disorder; or HAD).

Conclusions:  This is the first time that HIV DNA levels were shown as a continuum across neurocognitive diagnoses with low levels in normal cognition; moderate levels in minor cognitive-motor disorder; and high in HAD. These data support a hypothesis that HIV DNA may be an important factor in neuropathogenesis.