George Todak

An Observed Performance Test of Medication Management Ability in HIV: Relation to Neuropsychological Status and Medication Adherence Outcomes

Neuropsychological assessment may identify mild deficits in HIV-infected persons, but it is sometimes unclear if such deficits compromise functional competencies, such as the ability to adhere to complex medication regimens. We examined the relationship between neuropsychological status (NP), observed performance on a medication management test (MMT), and antiviral medication adherence as elicited in a 3-day recall measure. Two samples of HIV+ subjects (n = 20, n = 41) were used to develop and validate the MMT. An additional 57 HIV+ patients taking antivirals were assessed to examine NP, MMT, and adherence outcomes. NP performance was scored according to age- and education-based norms. Adherence was assessed by comparing reported medication use to medication insert information. Poorer performance on the MMT was associated with scores <−1 SD below norms in tests of memory (RAVLT), executive function (Odd Man Out), and psychomotor skill (Grooved Pegboard). Half the sample made >1 adherence error, as reported in the recall measure. Number of errors was related to both NP and MMT performance. Deficits identified in NP assessment and captured in an observed performance test of medication management are related to HIV medication adherence.

Mortality risks in gay men with human immunodeficiency virus infection and cognitive impairment

We obtained data from 111 gay men who entered a longitudinal study of the natural history of human immunodeficiency virus (HIV) without clinical evidence of acquired immunodeficiency syndrome (AIDS), and examined them regularly over a 36-month period. Using a Cox proportional-hazard regression model to compare cumulative risk of mortality in subjects with and without cognitive impairment and several putative risk factors present at baseline, we found that the mortality risk ratio (RR) associated with poor neuropsychologic test performance was significantly increased (RR = 2.9; 95% confidence interval [CI], 1.1 to 7.8), and increased further (RR = 4.1; 95% CI, 1.3 to 12.5) when adjusted for other factors associated with mortality (a history of a disturbance in movement or gait, CD4-lymphocyte and red blood-cell counts, and age). A significant increase in symptoms related to cognitive impairment and gait, a decline in neuropsychologic test performance, and declines in CD4-lymphocyte and red-cell counts occurred over the study period. A second model was constructed to adjust for changes in CD4-lymphocyte and red-cell counts, age, medical stage, and motor symptoms over the study period, but the mortality RR for poor neuropsychologic test performance at baseline changed very little (RR = 4.7; 95% CI, 1.5 to 14.9). We conclude that the presence of cognitive impairment, manifest by poor neuropsychologic test performance in both asymptomatic and symptomatic gay men with HIV infection, is associated with a significantly increased risk of death. This effect progresses in parallel with the immunologic and systemic effects of HIV.

Oral manifestations of HIV infection in homosexual men and intravenous drug users: Study design and relationship of epidemiologic clinical, and immunologic parameters to oral lesions☆

This article describes the baseline findings from a study designed to compare the oral manifestations of HIV infection in homosexual men and intravenous drug users. Both seropositive and seronegative persons were studied. A standard examination instrument was developed to record indexes of oral disease as well as to record the presence of oral lesions. The two groups differed in terms of education, race, socioeconomic status, employment status, housing, and smoking experience. The prevalence and type of oral lesions differed in the two seropositive groups. In seropositive homosexual men, white lesions on the tongue (28.4%) predominated; whereas for the seropositive intravenous drug users, oral candidiasis (43.0%) and gingival marginal erythema (33.3%) were most often detected. We also observed that seronegative intravenous drug users displayed a greater number of oral lesions than seronegative homosexual men. For seropositive homosexual men, lesion presence was significantly associated with decreased levels of CD4; positive associations were seen with current smoking, antiviral drug use, and antibiotic use, and a negative association was observed with current employment. In contrast, only exposure to antiviral drugs was significantly correlated with lesion presence for seropositive intravenous drug users. This baseline analysis from our longitudinal study suggests clear differences in oral manifestations of HIV infection between seropositive homosexual men and intravenous drug users and between seronegative homosexual men and intravenous drug users. Among other parameters, it is apparent that lifestyle, access to health care, and the condition of the oral cavity before infection influence the development of oral lesions in persons with HIV infection.

A randomized clinical trial of CPI-1189 for HIV-associated cognitive-motor impairment.

Background: CPI-1189 is a compound with antioxidant properties that blocks tumor necrosis factor-α (TNFα) effects in animal models. It has neuroprotective properties in model systems for HIV-associated neurotoxicity and thus is a candidate for neuroprotective therapy in humans with HIV-associated CNS disease. Objective: To assess the tolerability and safety of CPI-1189 in treating HIV-associated cognitive–motor impairment. Methods: Sixty-four subjects with mild to moderate HIV-associated cognitive–motor impairment were randomized to receive either placebo or 50 or 100 mg daily of CPI-1189 in addition to optimal HIV therapy. Subjects were followed prospectively in a double-masked study for 10 weeks. The primary assessment was tolerability and safety of the compound. Secondary objectives examined neuropsychological and functional change associated with this treatment. Results: The study compound was well tolerated, with 91% of CPI-1189-treated subjects and 76% of placebo-treated subjects completing the trial. Skin rash was seen equally in placebo and active arms, but the only study withdrawals due to skin rash occurred in CPI-1189-treated subjects (n = 2). One subject developed a cataract on drug (100 mg/day). CD4 lymphocyte counts and plasma HIV viral load remained stable in all groups throughout the trial. No significant treatment effects were observed on the change in composite Z-scores for eight neuropsychologic measures (NPZ-8). The Grooved Pegboard Test (nondominant) showed improved performance with CPI-1189 at 100 mg/day (p = 0.01), but no other neuropsychometric or functional measures demonstrated significant improvement. Conclusions: CPI-1189 was well tolerated in HIV subjects with cognitive–motor disorder. This study was not powered to conclusively determine efficacy and showed no consistent treatment-associated improvement in cognitive or functional measures.

Neuropsychological Changes in a Prospectively Followed Cohort of Homosexual and Bisexual Men With and Without HIV Infection

Article abstract-We evaluated neuropsychological test performance of 168 homosexual and bisexual men with and without human immunodeficiency virus (HIV) infection (113 HIV+ subjects and 55 HIV- controls) over 4.5 years of semiannual follow-up. Analyses of the longitudinal data were performed by applying generalized estimating equations (GEEs) to regression analyses with repeated measures. Compared with the HIV- men, the HIV+ subjects performed more poorly on memory testing. Performance on all tests tended to improve over time, but this improvement was attenuated or eliminated in the HIV+ group for tests of language and attention. Within the HIV+ subjects, improvement over time in tests of memory, executive function, language, and attention was attenuated or eliminated in patients with lower CD4 levels; more advanced HIV disease was associated with poorer memory and executive function and with attenuated or reduced learning effects for memory, motor speed, and language tests. Clinically significant neurologic findings were associated with worse memory and orientation and with attenuated or reversed learning effects for memory, language, and attention tests. There were 33 deaths in the HIV+ group. In the men who died, there was more rapid decline in executive, language, and attentional test performance. These observations remained significant after controlling for HIV disease severity. We conclude that HIV infecting the CNS results in progressive cognitive change that is closely associated with neurologic findings. In addition, our findings suggest a relation between more rapid cognitive progression and death. NEUROLOGY 1995;45: 467-472

Neurologic Signs and Symptoms in a Cohort of Homosexual Men Followed for 4.5 Years

Article abstract—We traced the development of neurologic impairment in 207 homosexual men (123 human immunodeficiency virus [HIV]-positive and 84 HIV-negative controls) over 4.5 years of follow-up. We applied generalized estimating equations to logistic regression analyses with repeated measures to examine the differences between HIV-positive and HIV-negative subjects with respect to the likelihood of developing six neurologic outcomes derived from a factor analysis, significant neurologic impairment (modified Kurtzke disability score of ≥3), or significant neuropsycholog-ical impairment. We found that, over time, HIV-positive subjects were more likely to develop clinically significant ex-trapyramidal signs and frontal release signs than HIV-negative subjects. Controlling for age or education, as CD4 count declined, the odds of developing significant extrapyramidal signs, abnormalities in alternating movements, frontal release signs, and a Kurtzke score ≥3 increased. HIV-positive subjects were almost five times as likely (odds ratio [OR], 4.6; 95% CI, 1.6 to 13.4) as HIV-negative subjects to stay the same or worsen neurologically on the next visit, and those with CD4 ≥200 were 4.8 times as likely (OR, 4.8; 95% CI, 2.2 to 10.7) to maintain or worsen neurologically relative to those with higher CD4 counts. We conclude that neurologic impairment becomes increasingly apparent over time in HIV-infected men, especially in those with low CD4 counts.

Medication management skill in HIV: I. Evidence for adaptation of medication management strategies in people with cognitive impairment. II. Evidence for a pervasive lay model of medication efficacy.

People with HIV-related cognitive impairment may change the way they manage medication regimens, relying on a fixed medication schedule each day to avoid missed doses. Using a medication recall diary, we identified people who took medication on exactly the same schedule over 3 days and those with more variable medication schedules. Patients with low scores on executive and psychomotor tests were more likely to report fixed medication schedules; memory performance, by contrast, was not associated with reported medication regimen. Patients with low scores on executive and psychomotor tests were also less accurate in pouring medicines in the Medication Management Test. More than three fourths of these HIV+ patients assumed that medicines with higher milligram dosages were stronger than medicines with smaller milligram dosages, even across different classes of medicines. In a non-HIV sample, 28% endorsed the belief, suggesting it is a widespread way of thinking about medication strength. A performance test of medication management sheds light on the ways patients take medicines and how beliefs about medicines affect medication regimens.

Time allocation and disability in HIV infection: A correlational study

Abstract Disability in disease is likely to be reflected in daily time use. Subjects seropositive for human immuno deficiency virus (HIV) were expected to show reduced time in physically demanding activities and increased time in unavoidable obligatory activities, compared to seronegative controls. In addition, deficits in neurologic and neuropsychological function were expected to affect different components of everyday activity. To explore these hypotheses, a daily time diary was filled out by respondents in an established gay and bisexual mens cohort (n=72). Seropositive subjects spent a significantly greater proportion of the waking day resting, in at‐home activities, and in non‐work activities. Seropositive subjects were also awake, on average, one hour less than seronegative subjects. The two groups did not differ in time allocated to basic self‐care activities. Controlling for number of HIV symptoms, neurological and neuropsychologic deficits are associated with time allocated to important everyda...

The stability of neuropsychological test performance in a group of parenteral drug users

The stability of neuropsychological performance in a sample of drug abusers was investigated for a wide range of neuropsychological tests, using a test-retest paradigm with 16 parenteral drug users. The battery administered included tests of general intellectual function, abstract reasoning, verbal memory, language, attention, visuospatial ability, set switching, speeded performance, and manipulative dexterity. Stability coefficients were of a moderate to high magnitude for most of the tests and were comparable to coefficients found in other studies of non-drug-users. Two exceptions, however, were the Selective Reminding Test and the Perdue Pegboard. Possible reasons for instability with these two tests are discussed. It is concluded that neuropsychological investigations of drug abusers can yield consistent and reliable data, although further studies should employ alternative and/or supplementary measures of verbal memory and motor function.