Youth and primary caregivers completed DSM-IV
–referenced rating scales. The Child and Adolescent Symptom Inventory–4R (CASI-4R)13–15
is a validated 147-item, caregiver-completed scale for evaluating children and adolescents aged 5 to 18 years; individual items correspond to DSM-IV
symptoms and are rated on a 4-point Likert scale (0 indicates never; 3, very often). Items are summed to generate a symptom severity score for each disorder. Items rated “often” and “very often” are used to determine whether an individual meets DSM-IV
symptom criteria for a specific disorder (ie, symptom criteria). Finally, for each disorder, informants are asked whether symptoms interfere with social or academic functioning (ratings of “often” or “very often” indicate functional impairment). Individuals who have the prerequisite number of DSM-IV
symptoms (symptom criteria) plus functional impairment meet clinical criteria for a specific disorder. Primary caregivers also completed a validated parallel self-assessment tool, the Adult Self-report Inventory–4.16
Youth self-reports of psychiatric symptoms were collected by 2 instruments according to prespecified age groups. The Youth’s (Self-report) Inventory–417,18
is a 128-item self-report rating scale for youth aged 12 to 18 years, with items parallel to those in the CASI-4R. The Child (Self-report) Inventory–419
contains 34 items parallel to the Youth’s (Self-report) Inventory–4 but for young children (8–11 years) and does not assess impairment. All screening tools used were available in validated Spanish translations.
Two subscales of the Wechsler Intelligence Scale for Children–Fourth Edition Integrated (WISC-IV)20
were administered to provide an indication of the participant’s working memory (Letter-Number Sequencing) and processing speed (Coding Recall). These subscales were selected to minimize language, cultural, or educational influences and response burden.
Additional measures were completed by caregivers. These included assessment of the youth’s quality of life, including overall, physical, and emotional health and performance of daily activities (scored 0–10, with 10 representing the best health); the School Functioning Scale,21
which assesses academic performance, special education, and grade retention (scored 0–10; a high value indicates poor functioning); the Social Functioning Scale,21
which assesses peer relations (scored 0–10; a high value indicates poor functioning); and the Parent Questionnaire,21
which obtains information about treatment history (eg, psychotropic medication, behavioral therapies, and hospitalization).
Laboratory data related to HIV infection included lifetime nadir and current CD4 counts and CD4 percentages and lifetime peak and current viral loads. Each participant’s HIV classification and treatment data included CDC-C classification, current receipt of HAART (defined as ≥3 antiretroviral medications from ≥2 classes), years of HAART exposure, and current or past exposure to efavirenz. Information regarding family demographics and characteristics, including the participant’s relationship to household members who were known to be HIV+, was also recorded.
We assessed the presence and severity of 7 psychiatric conditions within 4 broad psychiatric domains: attention-deficit/hyperactivity disorder (ADHD), depression (major depressive episode or dysthymia), disruptive behavior disorder (oppositional defiant disorder [ODD] or conduct disorder [CD]), and anxiety (generalized anxiety disorder or separation anxiety disorder). Outcomes included symptom severity scores (youth and caregiver assessments) for psychiatric symptoms, WISC-IV sub-scale scores, academic and social functioning, and QOL.
We explored the relationship between the child’s psychiatric status and the child’s severity of HIV disease by using general estimating equation linear regression models for continuous outcomes and multiple logistic regression analyses for dichotomous outcomes, controlling for a priori potential confounders: age group (<12 vs ≥12 years), sex, relation to caregiver (whether the caregiver was a biological parent), caregiver educational level, life stressors in the preceding year (≥1 vs none), and caregiver psychiatric symptoms (ie, whether the caregiver met symptom criteria for ≥1 targeted disorder vs none). Participant IQ was not considered a potential confounder because an IQ of 70 or lower was an exclusion criterion and an IQ higher than 70 is minimally correlated with psychiatric symptoms.
A separate analysis was conducted for each combination of a psychiatric condition and a group of HIV disease severity markers reflecting past HIV disease (peak HIV RNA VL, nadir CD4 percentage, age [in years] at peak RNA VL, and nadir CD4 percentage) and current HIV disease (HIV RNA VL and CD4 percentage at study entry). For all analyses, we controlled for the absence or presence of CDC-C; therefore, the estimated effects of the other markers are over and above any effects of that variable. All models also evaluated possible links between prior use of efavirenz, a nonnucleoside reverse transcriptase inhibitor (NNRTI) considered to be associated with increased neuropsychiatric complications, and psychiatric outcomes. In a sensitivity analysis, we explored the independent effect of each of the HIV disease markers after controlling for personal and family characteristics and efavirenz exposure. Finally, to understand the ameliorating effects of treatment, we explored regression models based on current HIV treatment: HAART with a protease inhibitor (PI) only, HAART with an NNRTI only, HAART with a PI and an NNRTI, and past HIV treatment (≥5 years of HAART or ≥5 years of treatment with a PI).
In hypothesis testing, 2-sided P<.05 was considered statistically significant. However, given the large number of models fitted and predictors evaluated, the results are considered exploratory, and particular attention in interpretation was paid to consistency across analyses. All analyses were performed using SAS statistical software, version 9.1 (SAS Institute, Inc), and are based on data submitted as of October 2007.