Human immunodeficiency virus (HIV)-associated cognitive impairment, a significant cause of morbidity, affects up to 30% of HIV-infected people. Its prevalence doubled as patients began to live longer after the introduction of highly active retroviral therapy. Women are now one of the fastest growing groups with acquired immunodeficiency syndrome (AIDS) in the United States and Puerto Rico, but relatively little is known about the prevalence and characteristics of cognitive dysfunction in HIV-infected women. In this study the authors investigated its prevalence in a group of HIV-1-seropositive Hispanic women in Puerto Rico. Forty-nine women with a nadir CD4 cell count of < or = 500 cells/mm3 were enrolled. Cognitive impairment was defined according to the American Academy of Neurology criteria for HIV dementia as modified to identify an "asymptomatic cognitively impaired" group. Observed prevalence was compared with prevalence in other populations in United States, Europe, and Australia. Differences in clinical markers and neuropsychological test performance among the cohort stratified by cognitive impairment were tested. Cognitive impairment was observed in 77.6% (38/49) of cases; asymptomatic cognitive impairment in 32.7% (16/49); minor cognitive motor disorders in 16.3% (8/49); and HIV-associated dementia (HAD) in 28.6% (14/49). Cognitive impairment did not correlate with age, CD4 cell count, viral load, or treatment modality. The cross-sectional prevalence of HIV-associated cognitive impairment was 77.6% (28.6% for HAD). These findings should enhance awareness of the prevalence of HIV-associated cognitive impairment, both clinically apparent and "asymptomatic," in Hispanic women and lead to improvements in areas such as education and compliance and to reevaluation of treatment interventions.

HIV infection is increasing in minority groups, particularly in African American and Hispanic women. Although the incidence of HIV dementia has decreased since the advent of highly active antiretroviral treatment, prevalence of neurocognitive complications has increased as patients are now living longer. This study's purpose was to determine the psychometric properties of the Spanish-language HIV Dementia Scale (HDS) in a group of HIV-infected women. We recruited 96 women: 60 HIV-seropositive and 36 HIV-seronegative. Modification of the HDS into a Spanish-language version consisted of translating the instructions, substituting four words in Spanish (gato, media, azul, piña), increasing 1 second in the psychomotor speed because the Spanish alphabet has more letters than the English alphabet, and not offering clues for memory recall. Cognitive impairment (CI) was defined according to the modified American Academy of Neurology HIV-dementia criteria including an asymptomatic CI group. Statistical analysis consisted of analysis of variance to determine group differences and receiver operator characteristics (ROC) to determine the optimal cutoff point for the screening of CI. HDS-Spanish total score and subscores for psychomotor speed and memory recall showed significant differences between HIV-seronegative and women with HIV-dementia (p < 0.001) and between HIV-seropositive women with normal cognition and those with HIV-dementia (p < 0.001). The optimal cutoff point of 13 or less had performance characteristics of 87% sensitivity and 46% specificity for HIV-associated CI (50.0% positive predictive value, 85.0% negative predictive value). The HDS-Spanish translation offers a useful screening tool with value for the identification of Hispanic women at risk of developing HIV-associated symptomatic neurocognitive disturbances.

Background Insulin resistance occurs in HIV-infected individuals and is associated with HIV-associated neurocognitive disorders (HAND). However, the mechanisms involved are not well understood. Previously we showed a correlation between soluble insulin receptor (sIR) and HAND. Here we investigated if binding of free insulin to sIR and soluble insulin-like growth factor-1 receptor (sIGF1-R) levels are associated with sIR in HAND. Methods Thirty-four (34) HIV-seropositive women stratified by cognitive status and 5 HIV-seronegative women were evaluated. In a subgroup of 20 HIV positive and 5 donors, binding of plasma insulin to sIR was determined by ELISA assay of residual insulin levels in plasma immuno-depleted with anti–IR-monoclonal antibody-Sepharose beads. sIR and sIGF1-R levels were determined by ELISA. Nonparametric statistics were used. Results Higher percentages of insulin bound to sIR significantly correlated with sIR levels and were associated with HAND status. Higher levels of plasma sIGF1-R had a positive correlation with sIR levels (p=0.011) and were associated with HAND (p=0.006). No correlations were observed with age, viral-immune profile, antiretroviral therapy, or TNF. Conclusion This study suggests that changes in sIGF1-R levels and insulin binding to sIR may contribute to HAND.

HIV-associated neurocognitive disorders (HAND) continue to be a neurological complication of HIV infection in the era of combined antiretroviral therapy (cART). Hippocampal neurodegeneration and dysfunction occurs as a result of HIV infection, but few studies to date have assesses spatial learning and memory function in patients with HAND. We used the Memory Island (MI) Test to study the effects of HIV infection, Apolipoprotein E (ApoE) allele status, and CSF ApoE protein levels on spatial learning and memory in our cohort of Hispanic women. The MI Test is a virtual reality-based computer program that tests spatial learning and memory, and was designed to resemble the Morris Water Maze (MWM) test of hippocampal function widely used in rodent studies. In the current study, HIV-seropositive women (n=20) and controls (n=16) were evaluated with neuropsychological (NP) tests, the MI Test, ApoE, and CSF ApoE assays. On the MI, the HIV-seropositive group showed significant reduced learning and delayed memory performance compared with HIV-seronegative controls. When stratified by cognitive performance on NP tests, the HIV-seropositive, cognitively impaired group performed worse than HIV-seronegative controls in ability to learn and in the delayed memory trial. Interestingly, differences were observed in the results obtained by the NP tests and the MI Test for ε4 carriers and non-carriers: NP tests showed effects of the ε4 allele in HIV-seronegative women but not HIV-seropositive ones, whereas as the converse was true for the MI Test. Our findings suggest that the MI test is sensitive in detecting spatial deficits in HIV-seropositive women, and that these deficits may arise relatively early in the course of HAND.

YWHAE (14-3-3ε) protein levels are considered to be a reliable biomarker for neurodegeneration. The YWHAE protein interacts both directly and indirectly with human immunodeficiency virus (HIV) accessory proteins, leading to cell death. The purpose of this study was to examine the relationship between YWHAE polymorphisms and HIV-associated neurocognitive disorder (HAND) and the relationship between YWHAE protein levels and HAND. A cross-sectional study using random samples of HIV-seropositive (n=20) and HIV–seronegative (controls) (n=16) women from the Hispanic-Latino Longitudinal Cohort of Women was conducted. Individuals who are HIV-seropositive and heterozygous at the rs4790084/rs1204828 loci in the YWHAE gene were 3X more likely to display reduced cognitive functioning, to have received a HAND diagnosis, and to have less YHWAE protein expressed than homozygotes. Western blots from cerebral spinal fluid (CSF) indicate that the HIV-seropositive women with HAND expressed 4.5X less YWHAE compared to HIV-seropositive cognitively normal women (94% sensitivity, 84% specificity; HIV-seropositive vs. controls). Therefore, polymorphism in YWHAE may be a genetic risk factor for HAND and levels of YWHAE protein are a likely biomarker for neurocognitive status in HIV-seropositive women.