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Objectives: Cognitive impairment remains frequent in HIV, despite combination antiretroviral therapy (cART). Leading theories implicate peripheral monocyte HIV DNA reservoirs as a mechanism for spread of the virus to the brain. These reservoirs remain present despite cART. The objective of this study was to determine if the level of HIV DNA in CD14(+) enriched monocytes predicted cognitive impairment and brain injury., Methods: We enrolled 61 cART-naïve HIV-infected Thais in a prospective study and measured HIV DNA in CD14(+) enriched monocyte samples in a blinded fashion. We determined HAND diagnoses by consensus panel and all participants underwent magnetic resonance spectroscopy (MRS) to measure markers of brain injury. Immune activation was measured via cytokines in cerebrospinal fluid (CSF)., Results: The mean (SD) age was 35 (6.9) years, CD4 T-lymphocyte count was 236 (139) and log10 plasma HIV RNA was 4.8 (0.73). Twenty-eight of 61 met HAND criteria. The log10 CD14(+) HIV DNA was associated with HAND in unadjusted and adjusted models (p = 0.001). There was a 14.5 increased odds ratio for HAND per 1 log-value of HIV DNA (10-fold increase in copy number). Plasma CD14(+) HIV DNA was associated with plasma and CSF neopterin (p = 0.023) and with MRS markers of neuronal injury (lower N-acetyl aspartate) and glial dysfunction (higher myoinositol) in multiple brain regions., Interpretation: Reservoir burden of HIV DNA in monocyte-enriched (CD14(+)) peripheral blood cells increases risk for HAND in treatment-naïve HIV+ subjects and is directly associated with CSF immune activation and both brain injury and glial dysfunction by MRS.

International studies of HIV-associated neurocognitive disorder (HAND) are needed to determine the viral and host factors associated with cognitive impairment particularly as more than 80% of HIV+ subjects reside in resource-limited settings. Recent diagnostic nomenclature of HAND requires comparison of cognitive performance specifically to local normative data. To evaluate this need for local norms, we compared normative data obtained locally in Thailand to Western norms. The current study examined cognitive performance in 477 seronegative Thai participants (male = 211, female = 266) who completed a battery of tests sensitive to cognitive changes in HIV. The cohort was divided into three age brackets (20-34; 35-49; 50-65 years) and four educational levels (no education or primary education, less than secondary certificate, high-school/associates degree, bachelor's degree or greater). The Thai cohort was compared (using analysis of covariance, ANCOVA) on a number of measures to a seronegative US cohort (n = 236; male = 198, female = 38) to examine cultural differences in performance. Normative data are provided with age and education stratification. The Thai and US groups performed significantly differently on all neuropsychological measures with the exception of verbal fluency. The Thai group performed better on measures of verbal learning (p < .001) and memory (p < .001) and measures of psychomotor speed (p < .001). Education was a more powerful predictor of performance in the Thai cohort than in the US group. These results highlight the continued need for the development of normative data within local populations. The use of Western norms as a comparison group could lead to inaccurate identification of HAND in culturally distinct groups.

The effect that HIV type 1 (HIV) has on neurocognition is a dynamic process whereby peripheral events are likely involved in setting the stage for clinical findings. In spite of antiretroviral therapy (ART), patients continue to be at risk for HIV-associated neurocognitive disorders (HAND), which might be related to persistence of inflammation. In a yearly assessment of HIV DNA levels in activated monocytes, increased HIV DNA copies were found in patients with persistent HAND. Furthermore, activated monocytes from patients with high HIV DNA copies secreted more inflammatory cytokines. Since these activated monocytes traffic to the CNS and enter the brain, they may contribute to an inflammatory environment in the CNS that leads to HAND.

Both HIV and aging impact performance on neuropsychological testing; however, evidence for differences between HIV effects in younger compared to older subjects (interaction effects) is limited and the findings have been inconsistent. Coexisting morbidities that contribute to cognitive impairment in HIV include those not directly referable to infection, per se, and are more prevalent with advancing age, increasing the likelihood that HIV and age effects may be largely independent. As individuals survive with HIV into geriatric age groups, greater clarity on these relationships is essential. We present cross-sectional data from a large (n = 450) cohort designed to analyze HIV, age, and interaction effects using a well-matched cohort of HIV-negative individuals. Results reveal limited evidence for interaction effects between HIV and age on neuropsychological performance. We conclude that older age does not significantly influence neuropsychological performance among HIV patients when seronegative controls are largely composed of individuals from a similar socioeconomic background.

This research is a cross-sectional study to determine the frequency of neurocognitive impairment and psychiatric comorbidity among Thais maintained on highly active antiretroviral therapy (HAART) with undetectable plasma human immunodeficiency virus (HIV) RNA in the 2NN Cohort. Sixty-four subjects were evaluated with neurological examinations, neuropsychological testing, and psychiatric questionnaires. Twenty-four subjects (37.5%) were found to have neurocognitive impairment, with 13 (20.3%), 10 (15.6%), and 1 (1.6%) classified as asymptomatic neurocognitive disorder (ANI), mild neurocognitive disorder (MND), and HIV-associated dementia (HAD), respectively. Three subjects (4.7%) had depression and no cases had significant symptoms of anxiety. A notable proportion of well-controlled individuals exhibited neurocognitive impairment. Anxiety and depression were uncommon.

Human immunodeficiency virus (HIV) DNA in peripheral blood mononuclear cells was previously associated with neuropsychological function. By including individuals encompassing the full range of HIV-1-associated neurocognitive disorders, this study reports results from subjects with normal cognition, minor cognitive motor disorder, and HIV-1-associated dementia. Individuals with normal cognition had relatively low HIV DNA levels compared to those with minor cognitive motor disorder and HIV-1-associated dementia. Neuropsychological deficits were significantly associated with entry HIV DNA in all domains. These findings demonstrate for the first time that the severity of HIV-1-associated neurocognitive disorders is proportional to the amount of circulating HIV DNA.

Human immunodeficiency virus (HIV) dementia remains as an important cause of neurological morbidity among HIV-seropositive (HIV+) individuals. Differences in the neuropsychological profiles between older and younger HIV+ individuals have not been examined extensively. The objective of this study was to examine the neuropsychological test performance between old and young HIV+ individuals (a) with and without cognitive impairment (total cohort) and (b) with dementia. One hundred thirty-three older (age >or= 50 years) HIV+ individuals and 121 younger (age 20 to 39 years) HIV+ individuals were evaluated with a standardized neuropsychological test battery. Differences between age groups in the mean z score for each neuropsychological test were determined. The older HIV+ (total) cohort had greater impairment in tests of verbal memory (P = .006), visual memory (P < .002), verbal fluency (P = .001), and psychomotor speed (P < .001) compared to the young HIV+ (total) cohort. After adjusting for differences in education, older HIV+ patients with dementia (n = 31) had a greater deficit in the Trail Making test Part B (P = 0.02) compared to younger HIV+ patients with dementia (n = 15). Age was associated with lower performance in tests of memory, executive functioning, and motor performance in older HIV+ individuals with and without cognitive impairment (total cohort), compared to younger HIV+ individuals. Among HIV+ patients with dementia, age may be associated with greater impairment in a test of executive functioning. These differences could be a result of advanced age itself or age-associated comorbidities such as coexisting cerebrovascular or neurodegenerative disease.

Low CD4 lymphocyte count was a marker for neurological disease in human immunodeficiency virus type 1 (HIV-1); but is now less common among patients with access to highly active antiretroviral therapy. In this study, the authors determine the reliability of self-reported CD4 nadir and its predictive value for neurological status. The authors identify a high degree of reliability (r = .90). After adjusting for age, current CD4 count, and duration of HIV-1, CD4 nadir relates to a current diagnosis of HIV-associated dimentia (HAD) (odds ratio [OR]: 1.395 (1.106-1.761), P = .005) and distal symmetric polyneuropathy (DSPN) (OR: 1.479 (1.221-1.769, P < .001).