Our sample consisted of 101 participants, including 26 individuals who are HIV+ with cocaine dependence (HIV+/CD+), 18 individuals who are HIV+ without cocaine dependence (HIV+/CD-), 30 individuals who are HIV-negative with cocaine dependence (HIV-/CD+), and 27 individuals who are HIV-negative without cocaine dependence (HIV-/CD-).
Inclusion/Exclusion Criteria. All participants were required to be 21 to ensure complete cognitive development and a maximum age of 55 to limit potential aging effects. Participants had to be fluent in English, travel to the study visits, and provide informed consent. Exclusion criteria were as follows: a positive urine drug screen, current or lifetime DSM-IV diagnosis of schizophrenia or psychosis, AIDS-defining CD4 count (< 200), current or history of dementia or other AIDS-defining CNS disorders, history of a head injury with a loss of consciousness for more than 30 minutes, or vision problems that eyeglasses or contact lenses could not correct.
All individuals in the cocaine-dependent groups (i.e., HIV+/CD+, HIV-/CD+) were required to meet DSM-IV criteria for a diagnosis of cocaine dependence within the past two years. Exclusion criteria were a current or lifetime DSM-IV diagnosis of abuse or dependence on opioids or methamphetamine; DSM-IV diagnosis of dependence on any other illegal or prescription drug within the past five years; and DSM-IV diagnosis of alcohol dependence within the past year. The specific substance use criteria are consistent with the existing literature [8, 32, 33], which has demonstrated the specific amount of time following abstinence from a substance in which the substance continues to impact an individual both behaviorally and neurochemically.
HIV+ groups were required to be adherent to HIV medications for the past three months, as verified by the Medication Adherence Self-Report Inventory (MASRI), have a CD4 count >200, and have an undetectable HIV RNA viral load (<50 copies/mL). The specific criteria for those in the HIV+ groups were set in place to ensure that all individuals with HIV were asymptomatic, according to the Center of Disease Control and Prevention (CDC) and the World Health Organization (WHO) HIV disease severity staging system . HIV-negative groups were required to provide documentation verifying that they were seronegative. For those unable to do so, a rapid oral HIV test was given to confirm their negative HIV status. Our aim with the extensive criteria was to ensure that other comorbidities could not better explain our findings. The HIV specific criteria are consistent with previous studies that aimed at minimizing confounding factors potentially related to HIV-associated neurocognitive disorders .
The authors' Institutional Review Boards approved this study. Participants were recruited from local clinics (i.e., Chicago Developmental Center for AIDS Research (D-CFAR), the UIC Infectious Disease Clinic, Ruth M. Rothstein CORE Center) within the very focused 560-acre Illinois Medical District located in Chicago’s Near West Side. Interested participants initiated contact with the study coordinator, who completed a phone screen with potential participants to assess for initial eligibility. If the individual met criteria based on the telephone screen and agreed to abstain from using any drugs or alcohol for 48 hours before their on-site screening, they were invited to schedule their first visit. At the beginning of the first visit, informed consent was obtained before completing any of the study procedures. The participant then completed a urine toxicology test and an alcohol breathalyzer test. If the individual did not pass the urine toxicology test or the alcohol breathalyzer test, the individual's visit ended and was rescheduled for a later date. If an individual passed the urine toxicology and breathalyzer procedures, the screening visit proceeded. Participants completed a series of clinical and demographic questionnaires to obtain information on demographics, medical history, psychiatric disorder history, drug use, and medication adherence (HIV+ groups). Participants also completed the Structured Clinical Interview for the DSM-IV-TR (SCID-IV-TR) and a fixed neuropsychological test battery. Participants were paid $30 for their participation.
Screening Measures. All participants completed a brief demographic questionnaire and the full Structured Clinical Interview for DSM-IV-TR (SCID-IV-TR)  to determine any psychiatric diagnoses that would make them ineligible for the current study (see Inclusion/Exclusion Criteria). Module E of the SCID-IV-TR was explicitly utilized to determine specific current and lifetime substance abuse and dependence. Participants also completed the KMSK (Kreek – McHugh – Schluger – Kellogg Scale) to assess current (i.e., within the past month) and historical substance use (i.e., within their lifetime). The KMSK provides critical values, calculated from the participant’s frequency (i.e., number of times used in past month and lifetime), amount of substance use or amount of money spent daily, and duration of use for each specific substance . A urine toxicology screen and breathalyzer were also given as all individuals could not be under the influence of any substance at the time of testing.
Medical Record Review. All participants provided a release of information for medical records to be obtained that are related to our study aims. For participants who are HIV-positive, HIV variables including date of HIV diagnosis, most recent (within the past six months) CD4 count, HIV RNA viral load (copies/mL), and current list of medications were all recorded. Participants who were HIV-positive also completed a Medication Adherence Self-Report Inventory (MASRI) to assess adherence to their HIV medication. For participants who are HIV-negative, if they could not confirm their HIV status with medical documentation within the past six months, participants were given the OraQuick© rapid HIV test to confirm their negative HIV status.
Neurocognitive Functioning. Trained research assistants administered a brief neuropsychological test battery to assess neurocognitive functioning. Two research assistants double scored all measures. To obtain an estimate of the participants' premorbid cognitive functioning, each participant completed the Wide Range Achievement Test, Fourth Edition: Word Reading subtest (WRAT-4: WR) . On this task, participants were provided a sheet of increasingly difficult words and were asked to read as many words as possible. This task provided a well-validated way to estimate premorbid cognitive functioning .
To assess executive functioning, we utilized both the Stroop Color and Word Test (Stroop) as well as the Trail Making Test (TMT). The Stroop Color and Word Test, Comalli-Kaplan version , consists of three trials. The Color-Naming trial (Trial 1) and the Word-Reading trial (Trial 2) are primarily measures of attention and processing speed. The Interference trial (Trial 3) is primarily a measure of response inhibition and cognitive flexibility. Completion time for each trial was recorded in seconds, with the discontinue rule being four minutes on each of the three trials. The number of errors made on each of the trials was also recorded. Errors were defined as those mistakes that participants did not self-correct. The existing norms for the Stroop have been found to over pathologize African Americans , which is the majority of our sample. Because the Kaplan-Comalli version of the Stroop Color-Word Test does not have up-to-date published norms representative of this study's sample, we utilized the raw scores instead of converting the raw scores to demographically corrected z-scores.
The Trail Making Test (TMT) has two parts, TMT-A and TMT-B. TMT-A consists of 25 total numbered circles in which a person draws a line connecting each of the numbered circles in numerical order. TMT-B consists of both numbers (1-13) and letters (A-L) in which a person is to draw a line connecting numbers and letters in order switching from a number to a letter (i.e., 1-A-2-B-3-C). The participant's completion time was recorded in seconds. The number of errors made was also recorded. An additional derived ratio score (B/A) was computed to measure executive functioning more directly while controlling for the impact of visual-motor speed [30, 31]. The TMT-A primarily measures visual-motor processing speed, and TMT-B primarily measures cognitive switching [41, 42]. We utilized the Heaton norms, which took sex, age, race/ethnicity, and level of education into consideration to convert raw scores to demographically corrected z-scores .
Chi-square tests were used to determine significant differences between categorical variables, and two-way analysis of variance (ANOVA) was used for all the continuous variables. For the HIV-positive participants, t-tests were used to determine if there were significant differences in the mean CD4 count, HIV RNA viral load (copies/mL), and years since HIV diagnosis. Levene's F test was used to determine if the variances between groups were equal.
A series of 2 (HIV+/HIV-) × 2 (CD+/CD-) analyses of covariance (ANCOVA’s) were used to test for differences between groups on completion time and the number of errors on the Stroop (i.e., Color-Word Reading, Word Reading, Color-Word Interference) while controlling for age and premorbid IQ. Although premorbid IQ was not significantly different between groups, it was significantly correlated with our dependent variables, and therefore it was included along with age in our model. Since we utilized demographically corrected z-scores for the TMT, we did not need to include age as a covariate. Therefore, we conducted a series of analyses of variance (ANOVA’s) to test the differences between groups on TMT-A and TMT-B z-scores, the number of errors, and the B/A ratio score. To further examine if the Stroop and TMT measures assessed similar underlying cognitive processes, we performed correlation analyses between the TMT and Stroop. To control for multiple comparisons, we utilized a Tukey’s HSD correction to determine the significance of these omnibus tests. For all statistical analyses, we utilized the Statistical Package for the Social Sciences (SPSS) 24.0.