The objective of the current study was to assess everyday functional ability in four groups of individuals stratified based upon their HIV status and history of METH dependence, using the UPSA-2 to assess the individual and interactive effects of HIV and METH dependence on specific and essential domains of everyday functioning. We hypothesized that participants with both HIV infection and a history of METH dependence would have lower scores on the UPSA-2 than subjects with either condition alone and non-infected non-METH dependent comparison subjects. A secondary aim was to assess to what extent performance on the UPSA-2 measures would correlate with HIV illness features , and METH use characteristics within our HIV+ and METH-dependent participants, respectively. This investigation was a component of the Translational Methamphetamine AIDS Research Center , which is a multi-project center grant focused on translational approaches to understanding the combined effects of HIV and methamphetamine dependence on brain structure and function. The UCSD Human Research Protections Program approved the study. All human participants in the TMARC cohort were included. Participants were stratified by HIV and METH dependence status into one of four groups: HIV−/METH− , HIV−/METH+ , HIV+/METH− , and HIV+/METH+ . HIV infection was determined by Enzyme-linked immunosorbent assay and a confirmatory Western blot. The presence and history of METH use disorders were determined via the DSM-IV criteria for METH abuse and dependence as assessed by the Composite International Diagnostic Interview Version 2.1 [CIDI; ]. Participants who met criteria for both lifetime METH dependence and METH abuse or dependence within the past 18 months were included in the two METH+ groups. Potential participants were excluded if they reported histories of psychosis or significant medical or neurological conditions known to affect cognitive functions.
To minimize the confounding effects of acute drug use ,cannabis vertical farming participants who tested positive for METH or any other illicit drugs were also excluded. In the first domain, comprehension and planning skills were assessed by having participants read a fictional article about the opening of a theme park and then described the activities at the park and planned a trip to the recreational facility. Financial ability was evaluated by a counting change task and having the subjects identify important aspects of a utility bill. Communication skills were assessed through role-playing tasks that asked participants to use telephone to schedule a medical appointment. The Transportation domain involved reading and interpreting a generic bus route and planning the use of a public bus system. Household skills were assessed by requiring preparation of a shopping list for a specific cooking task based on food items presented in a mock pantry. Finally, for the Medication Management domain, participants were required to organize a medication routine where they were asked to role-play how they would take a number of different medications over the course of a single day. Administration of the UPSA-2 requires about 30 minutes. Each of the UPSA-2 domains generates a raw score that is converted to a domain score ranging from 0 to 20 points. The 6 domain scores are summed to create a total UPSA-2 score up to a maximum of 120 points, with higher scores indicating better performance. For the purpose of examining the UPSA-2 measures in relation to HIV disease characteristics and METH use patterns, participant characterization data were drawn from the TMARC parent study. Selected HIV disease-related variables included current and nadir CD4+ T-cell counts, plasma viral loads, and self-reported duration of HIV infection. Self reported METH use characteristics were collected using a comprehensive timeline follow back procedure and included age of first use of METH, days since last use of METH, total days of METH use, and total quantity of METH used.UPSA-2 total and sub-scale scores were examined for outliers, normality of distribution, and homogeneity of variance. In order to preserve the relative value of these data points and retain power, outliers were truncated to within 3 standard deviations of the mean, per published methods . A total of ten outliers were truncated .
Main effects of HIV, METH, and their interaction on UPSA-2 performance were examined for the Total Score and sub-scale scores using Univariate Analysis of Variance . Three between-subjects factors were entered into the models, as well as their interaction: METH status , HIV status , and education level . Years of education was selected a priori as an additional between-subjects factor given the difference in education among the groups, the significant relationship between education and UPSA scores , and previous reports of a significant relationship between education and UPSA scores . Planned contrasts were conducted on the four groups. When other demographics were associated with the sub-scales, those factors were included in the analysis to account for their effects . Pearson’s correlation coefficients were used to assess the relationship among UPSA-2 scores and HIV disease characteristics as well as METH use features. An independent samples test was used to assess difference in UPSA-2 scores between participants with and without a detectable plasma viral load. The HIV viral load measure and METH use measures were significantly positively skewed; log transformations of those variables were thus entered into the analyses. All analyses were performed using SPSS 20. Significance values were set at p < .05, and effect sizes were calculated using partial Eta-squared and Cohen’s d.See Table 1 for demographic information and HIV and METH features. The groups did not differ by age or ethnicity, but a greater proportion of the HIV−/METH− group were women. The HIV−/METH+ group had significantly fewer years of education and lower scores on the Wide Range Achievement Test than the other three groups. Consistent with previous literature , all three risk groups had higher scores on a depression scale, the Beck Depression Inventory , than the HIV−/METH− group. Global Deficit Scores , a gross index of neurocognitive deficits , were lower in the HIV−/METH− group but not significantly different among the three risk groups. Participants in the METH groups had a higher prevalence of lifetime substance use disorder than the METH-negative groups. Ten participants had a positive urine toxicology for cannabis; these participants did not have significantly different UPSA-2 scores than the remainder of the cohort. Better-educated participants performed better on the Financial and Communication sub-scales , with a trend toward Medication Management and Comprehension sub-scales . Thus, education level was included as a between-subjects factor in the analyses.
Higher WRAT-4 scores were positively correlated with higher scores on the Medication Management, Financial, Communication, Transportation, and Household Management scales . Given that WRAT-4 performance is an index of premorbid verbal intelligence, which in turn is highly dependent on education level, including education in the analyses was intended to account for the group differences in premorbid intelligence as reflected by both education and WRAT-4 scores. Men and women did not differ on most UPSA-2 measures although women performed better than men on the Communication sub-scale. The analysis involving Communication was thus repeated with gender as a between-subjects factor in a univariate ANOVA to account for its influence. The two HIV+ groups did not differ on any HIV illness features,cannabis drying racks and the two METH+ groups did not significantly differ on self-reported METH use history and characteristics. Approximately 70% of the HIV+ subjects reported current use of ART medications ; this proportion did not differ in the METH− vs. METH+ groups nor did the groups significantly differ on duration of ART treatment. All participants were taking a nucleoside reverse transcriptase inhibitor ; 56% were also on a protease inhibitor ; 33% were on a non-nucleoside reverse transcriptase inhibitor ; 15% were on an integrase inhibitor ; and 6% were on an entry inhibitor . A small proportion of participants on ART had a detectable plasma viral load; these participants were equally distributed in the two METH groups.People with METH dependence evidence difficulty with tasks of daily living , as do those with HIV infection , and in combination these risk factors result in an additive effect on self-reported everyday functioning . However, the combined effect of METH dependence and HIV has not previously been investigated with the use of performance-based functional measures that are likely a better reflection of an individual’s actual real-world functioning than self-report. We expected that there would be an additive deleterious effect of METH and HIV given previous findings of worse neurocognitive impairment in dually-affected participants. Contrary to our hypotheses, people with both HIV infection and METH dependence showed impairment on a performance-based measure, the UPSA-2, which was equivalent to that evidenced by individuals with either condition alone. It is important to note that the three risk groups performed comparably and it is unclear why having two risk factors did not result in disproportionately worse performance relative to those with single risk factors.
The lower level of education in the HIV−/METH+ group does not account for the findings, nor does use of ART. The number of individuals with a detectable viral load despite ART use, which may reflect sub-optimal adherence to ART but may also indicate non-responsivity to ART, was not different in the two HIV groups. We were likely under powered to detect effects of ART non-adherence and differential effects of specific ART regimens. Although Blackstone and colleagues did observe additivity of HIV and METH on a composite measure of everyday functioning that was largely comprised of self-reported information , the present findings are consistent with an earlier report of a lack of additive effect of METH and HIV on self-reported measures of functioning . Our group and others have previously observed an additive effect of METH and HIV on neurological and neurocognitive functions , but the current results are consistent with findings based on other neurobehavioral and neuroimaging markers. For example, additive effects of HIV and METH were not observed for behaviors associated with frontal systems dysfunction, including sensation-seeking, impulsivity/disinhibition, and apathy; moreover, a similar pattern of results was observed for impulsivity/disinhibition such that an HIV-by-METH interaction revealed an effect of METH among HIV-negative participants but not in the HIV-positive group . There is also some neuroimaging evidence that the combination of these two conditions mitigates brain changes that are seen in HIV infection or METH dependence alone . Additionally, though not assessed in the current study, age may be relevant. Although some cognitive functions such as impulsivity and risky decision making may decrease with age in the general population , a recent study found that older HIV+ individuals with a history of METH dependence did have substantially poorer functioning than younger participants, possibly suggesting increased vulnerability to combined risk factors in the context of aging. The average age of the current sample was just 40 years thus we could not examine the effects of aging. Studies are in progress to further investigate the impact of aging on cognition and functioning in METH and HIV. An alternate reason that the dual-risk group does not appear to have worse everyday functioning than either risk group alone may be the fact that METH users who must manage their HIV disease face challenges of everyday living when compared to their METH– dependent, HIV-negative counterparts that force them to develop skills that would detected by the UPSA-2. For example, they must navigate the medical system in order to obtain and maintain healthcare—relevant tasks would include transporting themselves to medical appointments, managing extensive and sometimes complex medication regimens, and other challenges that could negatively impact treatment adherence . Therefore, participants in this group may be relatively “practiced” at meeting the demands of everyday living. Social factors may be relevant; e.g., having an HIV-positive partner could result in the modeling of adaptive health behaviors such as medication adherence and drug abstinence . A comparison of the demographic, HIV illness features, and METH use features of the current dually-affected cohort and the relevant cohort in the Blackstone et al. study suggests a somewhat more cognitively intact and healthier group in the current study with higher WRAT-4 scores, more education, higher CD4 counts, higher prevalence of ART use, and less METH use compared to the Blackstone et al. participants.