Over the last 10 years, the use of combination antiretroviral therapy has led to declines in the incidence of complications of human immunodeficiency virus (HIV) infection.^1-3 During this same period, the prevalence of neurologic disease has remained stable or increased,^4,5 suggesting that treatment of central nervous system (CNS) disease may be suboptimal. One explanation for this may be poor antiretroviral (ARV) penetration into the CNS. Pharmacodynamic models¹ and in vivo evidence² suggest that the tissue-specific concentrations of ARV drugs are important determinants of their effectiveness in that tissue. Whether this is true for specific tissues in humans has been difficult to demonstrate because of technical limitations in sampling and determining tissue drug concentrations and viral loads (VLs). Many investigators have speculated that ARV concentrations in the CNS may be particularly important in treating nervous system disease, but no widely accepted or clinically useful approach to estimating CNS effectiveness exists. This has impeded clinical progress in managing the neurologic complications of HIV.

Many practical clinical questions regarding the management of human immunodeficiency virus (HIV)–associated neurocognitive disorder (HAND) remain unanswered. We sought to identify and develop practical answers to key clinical questions in HAND management. Sixty-six specialists from 30 countries provided input into the program, which was overseen by a steering committee. Fourteen questions were rated as being of greatest clinical importance. Answers were drafted by an expert group based on a comprehensive literature review. Sixty-three experts convened to determine consensus and level of evidence for the answers. Consensus was reached on all answers. For instance, good practice suggests that all HIV patients should be screened for HAND early in disease using standardized tools. Follow-up frequency depends on whether HAND is already present or whether clinical data suggest risk for developing HAND. Worsening neurocognitive impairment may trigger consideration of antiretroviral modification when other causes have been excluded. The Mind Exchange program provides practical guidance in the diagnosis, monitoring, and treatment of HAND.

HIV can infect the brain and impair central nervous system (CNS) function. Combination antiretroviral therapy (cART) has not eradicated CNS complications. HIV-associated neurocognitive disorders (HAND) remain common despite cART, although attenuated in severity. This may result from a combination of factors including inadequate treatment of HIV reservoirs such as circulating monocytes and glia, decreased effectiveness of cART in CNS, concurrent illnesses, stimulant use, and factors associated with prescribed drugs, including antiretrovirals. This review highlights recent investigations of HIV-related CNS injury with emphasis on cART-era neuropathological mechanisms in the context of both US and international settings.

To determine the effects of hepatitis C virus (HCV) infection on neuropsychological (NP) performance. Cross-sectional analysis of a prospectively enrolled cohort. A total of 239 HIV-seropositive and 287 HIV-seronegative subjects enrolled in prospective cohort studies at a single center. Subjects underwent standardized assessments, including comprehensive neuropsychological testing, substance use inventory neuromedical examination, venipuncture, and lumbar puncture. HCV antibody was measured in serum. In seropositive individuals, HCV RNA was measured in plasma and cerebrospinal fluid (CSF). HCV-seropositive subjects performed worse on neuropsychological testing and were almost twice as likely to be diagnosed as globally impaired, compared with those who were HCV seronegative. In a multivariate analysis, HCV, HIV, and methamphetamine dependence were independently associated with worse performance, even after adjusting for Centers for Disease Control stage and antiretroviral use. HCV-RNA levels in plasma were higher in those with memory, but not global, impairment. In cerebrospinal fluid, HCV RNA was below 100 copies/ml in all specimens. In HIV-infected subjects, HCV was associated with higher levels of HIV RNA in CSF, but not in plasma. HCV was also associated with higher levels of monocyte chemotactic protein 1, TNF-α, and soluble TNF receptor II. HCV-seropositive subjects did not appear to have advanced liver disease. HIV, HCV, and methamphetamine independently injure the central nervous system, leading to global neuropsychological impairment. HCV may injure the brain by viral or immune-mediated mechanisms. HCV-associated brain injury may be preventable or reversible because HCV infection is potentially curable.

Macrophages express the chemokine receptor CCR-5, a coreceptor for human immunodeficiency virus (HIV) entry. This receptor is ligated by β chemokines