Although the incidence of HIV in the United States is higher among men compared to women, the global proportion of women versus men who are infected has been approximately 50% since the late 1990s. Women have been under-represented in neuropsychological studies of HIV. A small number of studies have reported a significantly higher prevalence of neurocognitive impairment among HIV+ women compared to HIV− controls regardless of symptom status and with or without an AIDS diagnosis. Impairment was most evident on psychomotor tasks. The risk of neuropsychological impairment was increased among HIV+ women not on antiretroviral therapy. Age and depressive symptoms also increase neurocognitive risk. New neurocognitive studies of ovarian steroid hormones, PTSD and other psychiatric conditions are critical for addressing potential female-specific aspects of HIV-Associated Neurocognitive Disorder. Such studies will also address questions regarding involvement of the hippocampus and verbal memory, which may be of particular significance among HIV+ women.

Substance abuse and co-infection with hepatitis C (HCV) are two highly relevant determinants of neurocognitive and neuroimaging abnormalities associated with HIV. Substance abuse and HCV are common in the HIV population and there is increasing evidence that the CNS is directly compromised by these comorbid conditions via additive or synergistic processes. In this article we review the current literature regarding mechanisms of neuronal injury as well as the neuropsychological and neuroimaging signatures associated with substance abuse and HCV status among HIV patients. We discuss specific methodological challenges and threats to validity associated with studies of HIV and comorbid substance use disorders or HCV and review potential strategies for minimizing their confounding effects. Efforts to understand the interactions between HIV, substance abuse and HCV co-infection will lead to more complete models of neuropathogenesis of HIV and a greater understanding of the variability in neuropsychological expression of HIV Associated Neurocognitive Disorder.

HIV+ substance-dependent individuals (SDIs) show emotional distress and executive impairment, but in isolation these poorly predict sexual risk. We hypothesized that an executive measure sensitive to emotional aspects of judgment (Iowa Gambling Task; IGT) would identify HIV+ SDIs whose sexual risks were influenced by emotional distress. We assessed emotional distress and performance on several executive tasks in 190 HIV+ SDIs. IGT performance interacted significantly with emotional distress, such that only in better performers were distress and risk related. Our results are interpreted using the somatic marker hypothesis and indicate that the IGT identifies HIV+ SDIs for whom psychological distress influences HIV risk.

HIV+ individuals have been shown to demonstrate deficits on the Iowa Gambling Task (IGT), a complex measure of "decision-making." Little remains known about what other neurocognitive processes may account for variability in IGT performance among HIV+ samples or the role of procedural learning (PL) in IGT performance. A sample of 49 HIV+ individuals with a history of substance use disorders was examined to explore the relationship between IGT performance and three measures of PL: The Rotary Pursuit, Mirror Star Tracing, and Weather Prediction tasks. We found no statistically significant relationships between IGT performance and any of the PL tasks, despite finding significant correlations among the PL tasks. This pattern of results persisted when analyzing IGT performance in various ways (e.g., performance on earlier trial blocks or impairment classifications). Although other nondeclarative processes (e.g., somatic markers) may be important for IGT performance, these findings do not support PL as an important component neurocognitive process for the IGT. Similarly, these results suggest that differences in PL performance does not account for the decision-making deficits or variability in performances observed on the IGT among HIV+ individuals with a history of substance dependence.