Neuroscience research in AIDS.

1. The human immunodeficiency virus invades the central nervous system early after infection where it later gives rise to cognitive, motor, and behavioral manifestations in children and adults. 2. Ranging from mild impairments to frank dementia, CNS manifestations can be diagnosed and measured with standard neuropsychological test batteries. 3. Great strides have been made with treatment: CNS manifestations are treatable, as are depression, psychosis, and delirium which sometimes accompany HIV disease at different stages. 4. With startling advances in antiretroviral therapy and lower mortality, patients face a constellation of new concerns stemming from HIV's transformation to a more chronic disease. 5. There are many compelling research directions ahead, including the psychosocial impact of living with HIV as a chronic disease, the development of medications expressly targeted to the CNS, and basic research on neuropathogenesis, including trafficking of virus into the CNS.

Randomized double-blind placebo-controlled trial of peptide T for HIV-associated cognitive impairment.

BACKGROUND: Cognitive impairment is a common consequence of human immunodeficiency virus (HIV) infection, and dementia is one of the diseases that defines the acquired immunodeficiency syndrome. Peptide T (d-ala-peptide-T-amide) has been reported to block the binding of gp120 to brain tissue and to protect neurons from the toxic effects of gp120 in vitro. In pilot studies, administration of peptide T to HIV-positive patients with cognitive impairment was associated with improvement in cognition and constitutional symptoms. OBJECTIVE: To determine whether the intranasal administration of peptide T would improve cognitive function of HIV-positive patients with cognitive impairment. PATIENTS AND METHODS: This was a 3-site, double-blind, placebo-controlled trial of peptide T given intranasally at a dosage of 2 mg 3 times a day for 6 months. Participants were HIV-seropositive persons with evidence of cognitive deficits on a screening test battery. Concomitant antiretroviral therapy was allowed. Randomization to the 2 study arms was balanced according to several stratification variables, such as CD4+ cell count, severity of cognitive impairment, and antiretroviral therapy at study entry. A comprehensive neuropsychological (NP) battery, which yielded 23 scores, was administered at baseline and the study end point. The primary outcome measure was a global NP score derived from the 23 standardized scores. The efficacy end point was the change in NP score at 6 months compared with baseline. Secondary efficacy measures were 7 cognitive domain scores and deficit scores of global and domain performance. The patients who completed the baseline and final NP evaluations (after at least 4 months in the randomized treatment arm) were included in the efficacy analyses. Additional analyses were conducted on subgroups of patients according to the CD4+ count and baseline NP deficit. The incidence of NP improvement in the 2 treatment arms was also compared. RESULTS: There was no statistically significant difference between the peptide T and placebo groups on the global NP change score, the individual domains, or the deficit scores. Because of an imbalance in the baseline CD4+ cell count between treatment arms, analyses were also adjusted for this variable. These CD4+-adjusted analyses suggested (P = .07; analysis of covariance [ANCOVA]) a greater improvement in the peptide T group. Subgroup analyses indicated a treatment effect for patients whose CD4 cell count was above 0.200 x 10(9)/L (200 cells/microL) at baseline. Moreover, peptide T treatment was associated with overall cognitive improvement in patients with baseline global deficit scores of at least 0.5, while overall deterioration was more common among the placebo group (P = .02; Mantel-Haenszel chi(2) test). CONCLUSIONS: Peptide T was not significantly different from placebo on the study primary end points. However, additional analyses indicated that peptide T may be associated with improved performance in the subgroup of patients with more evident cognitive impairment (ie, NP global deficit score > or = 0.5) or with relatively preserved immunological status (ie, CD4+ cell count > 0.200 x 10(9)/L).

Psychopharmacology in HIV-positive patients: research perspectives.

Psychotropic medications play an important role in the treatment of human immunodeficiency virus (HIV)-positive subjects suffering from neuropsychiatric disorders or other acquired immunodeficiency syndrome (AIDS)-related symptomatology. The quality of life of these patients can be significantly improved by the appropriate use of these agents. Various aspects of psychopharmacology that are relevant to HIV-positive patients include assessment of efficacy, tolerability, drug-drug interactions, and effects on cognition. These topics need further investigation and require focused research efforts. This report highlights current research needs and presents specific recommendations that emerged at a recent meeting on psychopharmacology for HIV-positive patients organized by the National Institute of Mental Health (NIMH).

Perspectives from the National Institute of Mental Health: Preventing or living with aids.

This article provides a succinct overview of the history and current and future research priorities of the Office on AIDS at the National Institute of Mental Health (NIMH). Throughout its history and currently, the Office on AIDS has encouraged and supported research on primary prevention of human immunodeficiency virus (HIV) transmission, effects of HIV disease on the central nervous system, and coping with the sequelae of infection. Future directions for the NIMH include the dissemination of research fmdings to the community, investigation of mechanisms for involving and retaining participants in large-scale vaccine trials, and continued attention to the prevention of HIV transmission through behavior change.