Phase I trial of interferon alfa-n3 in early-stage human immunodeficiency virus type 1 disease: evidence for drug safety, tolerance, and antiviral activity.

The safety and tolerance of interferon alfa-n3 (IFN-alpha n3) was tested in 20 adults with asymptomatic human immunodeficiency virus type 1 (HIV-1) infection (> 400 CD4 lymphocytes/mm3). IFN-alpha n3 was self-injected three times per week for 3-6 months: 5 patients received 1 mega-IU (MIU)/dose, 10 received 5 MIU/dose, and 5 escalated to their maximum tolerated dose. Subjects were evaluated every 2-4 weeks through 2 months after cessation of treatment. Neuropsychological tests were given at 3-month intervals. Markers of IFN activity, anti-IFN neutralizing antibodies, and antiviral response were measured monthly. IFN-alpha n3 was safe and well tolerated: influenza-like symptoms were uncommon, laboratory toxicity was minimal, no adverse neurobehavioral side effects were evident, and no patient developed neutralizing antibodies against IFN. IFN-alpha n3 induced IFN-specific biologic responses and dose-related antiviral activity against HIV-1. Subjects showed stabilization of CD4 cells for > 20 months. IFN-alpha n3 should be studied in combination with other antiretroviral agents and in persons with more advanced HIV-1 infection.

Neuropsychological effects of Interferon Alfa-n3 treatment in asymptomatic human immunodeficiency virus-1-infected individuals.

Eighteen asymptomatic HIV-1-infected (HIV+) individuals were evaluated neuropsychologically before and during Interferon Alfa-n3 treatment. All 18 were evaluated twice, and 9 were evaluated three times. Analyses revealed few significant effects of treatment on cognitive, motor, and affective function. Improvements occurred over visits on measures of attention and appeared to reflect practice effects. Decrements occurred over visits on measures of procedural and supraspan learning. Examination of the data suggested that decrements were due to procedural artifacts and were not medication effects. In contrast to prior studies reporting significant neuropsychiatric side effects of interferon alpha treatment, few such effects occurred when HIV+ individuals were treated with Interferon Alfa-n3 and were evaluated neuropsychologically in a systematic manner.

Reaction time slowing in HIV-1-infected individuals: role of the preparatory interval.

Psychomotor speed and directed attention were evaluated in 83 human immunodeficiency virus-1-infected individuals (HIV+) and 50 HIV-1 seronegative (HIV-) control participants using simple and choice reaction time (RT) tasks. The simple RT task included 1- and 3-s, irregularly varied preparatory intervals (PI) between the warning and target lights. Relative to the HIV- group, simple and choice RT were significantly slowed in the HIV+ group. Further, again relative to the HIV- controls, the HIV+ group did not show expected faster RT with increased response preparation time in the simple RT task. This also occurred in some HIV+ subjects who did not have psychomotor slowing. These findings suggest that RT performance in HIV-1-infected individuals may reflect separate processes associated with psychomotor slowing and impaired ability to direct attention. Possible neural mechanisms associated with control of these processes are discussed.

Working memory in individuals with HIV infection.

The central executive component (CE) of Baddeley's working memory model (Baddeley, 1992) was evaluated in 26 asymptomatic human immunodeficiency virus-infected individuals (HIV+) and 23 HIV-control subjects using a dual-task working memory paradigm. The HIV+ and HIV- groups showed an equivalent reduction in performance on both the primary task (visual vigilance) and the secondary task (letter span) when they were performed concurrently relative to when either task was performed alone. This result suggested normal CE functioning in these HIV+ subjects. In contrast, the HIV+ subjects had significantly longer response latencies on reaction time measures relative to the HIV- control group. These findings indicated that slowed processing in early stage HIV-infected individuals is not associated with a working memory deficit.

Measuring performance decrements in aviation personnel infected with the human immunodeficiency virus.

There is controversy over whether cognitive impairment occurs in early human immunodeficiency virus (HIV) disease. When impairment is reported, findings are typically subclinical, affect only a minority, and their relationship to occupational functioning has not been established. Despite such findings, it has been recommended that HIV-seropositive pilots be disqualified from flying. This paper reviews research relevant to measuring performance decrements in HIV-infected aviators. Based upon current data, we conclude that although subtle neurobehavioral dysfunction may occur in some asymptomatic HIV-seropositive individuals, there is no research which has demonstrated associated decrements in aviation-related skills. Thus, it may be premature to recommend medical disqualification of all HIV-seropositive aviators. We propose, instead, that sensitive neurocognitive measures, incorporated into a comprehensive neurodiagnostic evaluation, could be used to evaluate asymptomatic HIV-seropositive aviators. Only those who are impaired on evaluation would be disqualified from flying. Concurrently, research investigating the relationship between abnormalities and aviation abilities would be conducted.

Relating cognitive function to military aviator performance in early HIV infection.

There has been controversy about whether cognitive changes occur in early human immunodeficiency virus (HIV) disease. In those studies reporting cognitive changes, these are typically subclinical, and their relationship to daily and/or occupational functioning has not been addressed. The potential effects of changes may vary as a function of occupational demands. This is germane to military performance, where occupational demands cover a wide spectrum of complexity. In particular, such effects are important to consider in the many cognitively demanding specialties associated with military aviation. This paper will explore ways in which possible HIV-related military performance decrements in aviators may be measured empirically. First, studies from Walter Reed Army Medical Center (WRAMC), which have shown cognitive changes in early HIV disease, will be described. This will be followed by a summary of presentations and discussions at a conference in November 1990, entitled 'HIV and Military Performance: Assessment Methodologies' held at WRAMC. The third section of the paper will describe a programme of research, which is developing measures to detect cognitive difficulties in civilian aviators. The application of measures from this research to research on HIV will be discussed. Finally, a research programme being developed to examine the possible impact of HIV-related cognitive changes on military aviator performance will be described.

Neuropsychological performance, mood, and complaints of cognitive and motor difficulties in individuals infected with the human immunodeficiency virus.

Seventy-nine military medical beneficiaries infected with human immunodeficiency virus (HIV+) and 27 HIV-seronegative control subjects (HIV-) completed a neuropsychological evaluation and a semistructured interview inquiring about difficulties in function. More HIV+ than HIV- subjects reported difficulties. HIV+ subjects reporting difficulties were significantly more likely to be deficient on attention, response speed, motor function, and memory than those not reporting difficulties. Findings for early-stage HIV+ subjects were similar. HIV+ individuals who complained of difficulties reported depression and anxiety symptoms significantly more frequently than those who did not complain, but these symptoms were not related to neuropsychological performance. Complaints of difficulties by HIV+ individuals may reflect either actual neuropsychological deficiency or mood disturbance, but the effects of each appear to be independent.

Testing to detect brain damage: an alternative to what may no longer be useful.

Kane, Parsons, and Goldstein (1985) recently demonstrated that the Halstead-Reitan Battery, the Luria-Nebraska Neuropsychological Battery, and the Wechsler Adult Intelligence Scale are all equally effective when used to detect brain damage. This commentary raises the question of whether this type of testing and test development is still useful. Several arguments are made suggesting that it is not. First, it is shown that detecting brain damage alone is usually not clinically useful. Instead, it is argued that neuropsychological instruments more effectively contribute to clinical diagnosis and treatment when used to delineate cognitive function. Additionally, it is demonstrated that brain-damage detection has a number of pitfalls. A method to develop instruments to delineate cognitive function is proposed, and a recent example of such an approach is provided.

Microcomputer control of behavior and the acquisition of digital and analog data.

Advances in technology and decreasing costs are enabling microcomputers to displace more traditional devices in the scientific laboratory. The availability of various approaches to software-system development for the use of microcomputers in the on-line control of experiments has contributed to the trend. This report describes a software system developed to control conditioned behavior during schedules of reinforcement while simultaneously accumulating behavioral data and physiological (analog) data using a hardware system base on the Radio Shack TRS-80 Model I microcomputer. The software utilizes a high-level interpretive language (Microsoft BASIC), assembly language and compiled BASIC to attain an acceptable execution speed and ease of programming.

An analysis of problem areas and counseling experiences of gay white males.

An analysis of problem areas and counseling experiences of gay white males was performed in preparation for a larger study. Subjects were members of several gay organizations. A number of relationships among demographic variables and problem areas were found. Two factors, a general social functioning factor and a factor relating to acknowledging one's gayness to others (coming-out), accounted for almost 70% of the variance in a structure of problem areas. Approximately half of the respondents reported having had counseling experience. Of those reporting their satisfaction with the experience, the majority were satisfied. Results suggested that white, educated, middle-class gay males may not be underserved with respect to psychological service delivery.