An analysis of select emerging executive skills in perinatally HIV-1-infected children.

This study examined the effect of perinatal HIV-1 infection on emerging executive skills in children (n = 161) ages 8 to 12 years. HIV-positive (n = 76) and HIV-negative (n = 85) children were eligible to participate. The HIV-positive children included those who had experienced a CDC Class C event (greater severity, n = 22) and those who were HIV-positive but who had not experienced a CDC Class C event (less severity, n = 54). Measures of emerging executive functions completed by the children included subtests from the Developmental Neuropsychological Assessment (NEPSY), the Trail-Making Test-Part B, and a subtest from the Woodcock-Johnson Battery-Revised. Ratings of executive functions were obtained from caretakers using the Behavior Rating Inventory of Executive Functions. Generalized estimating equations methods, discriminate analyses, and global deficit score analyses were performed to determine whether differences emerged between the three clinical groups while using strict controls. The present results revealed significant group differences in unadjusted mean scores measuring executive functioning. However, such differences did not remain statistically significant when moderating variables were taken into consideration in the models. The apparent deficit in executive functioning for the HIV-positive children was found to be largely due to differential psychosocial and environmental factors rather than HIV disease and its severity, and in this cohort, the effects of HIV-1 infection on emerging executive functions appeared to be negligible when controlling for treatment and moderating psychosocial variables.

Characteristics of HIV infected adolescents in Latin America: results from the NISDI pediatric study.

OBJECTIVE: HIV-infected adolescents are a heterogeneous population; source of infection, immunodeficiency severity and antiretroviral (ARV) experience vary. Here, we describe youth followed in an observational study at Latin American sites of the NICHD International Site Development Initiative (NISDI). METHODS: The NISDI pediatric protocol is an ongoing prospective cohort study that collects demographic, clinical, immunologic, virologic and medication data. Youth were enrolled at 15 sites in Brazil, Argentina and Mexico between 2002 and 2006. HIV-infected subjects aged 12-21 years at the time of enrollment were analyzed. RESULTS: Data from 120 HIV-infected youth were analyzed. Sixty-nine (58%) had acquired HIV through vertical transmission (VT); 51(42%) via horizontal transmission (HT). Twenty-eight percent of the VT group were not diagnosed until they were ≥10 years of age. Ninety-one percent of the VT group and 46% of the HT were receiving ARV at enrollment. Modes of HT included sexual (ST), blood product transfusion (BPT) and unknown (U). Severe immunodeficiency was frequent (21%) in the ST group. Low BMI was frequent in the VT and BPT sub-groups. Utilization of HAART increased over the course of the study, but viral suppression was present in only 38% of the VT group and 37% of the HT group at study end. CONCLUSIONS: This cohort of HIV-infected adolescents in Latin America displayed a diverse epidemiologic pattern. Care providers must be prepared to address the diverse needs and challenges of this population. The levels of virologic suppression achieved were inadequate. Further research into appropriate interventions for this population is urgently needed.

Prevalence of pain and association with psychiatric symptom severity in perinatally HIV-infected children as compared to controls living in HIV-affected households.

This cross-sectional study evaluated the prevalence of pain and psychiatric symptoms in perinatally HIV-infected children at entry into P1055, a multicenter investigation of the prevalence and severity of psychiatric symptoms in HIV-infected children. Subjects 6-17 years of age and their primary caregivers were recruited from 29 International Maternal Pediatric Adolescent AIDS Clinical Trials sites in the USA and Puerto Rico. A total of 576 children (320 HIV and 256 HIV- children) were enrolled from June 2005 to September 2006. Subject self-reports of pain were measured by the Wong-Baker visual analog scale and Short-Form McGill Pain Questionnaire. Symptomatology for anxiety, depression, and dysthymia was assessed through Symptom Inventory instruments. Caregiver's assessment of their child's pain and psychiatric symptomatology was similarly measured. Logistic regression models were used to evaluate predictors of pain. We found that a higher proportion of HIV-infected than uninfected subjects reported pain in the last two months (41% vs 32%, p=0.04), last two weeks (28% vs 19%, p=0.02), and lasting more than one week (20% vs 11%, p=0.03). Among HIV-infected youth, females (OR=1.53, p=0.09), White race (OR=2.15, p=0.04), and Centers for Disease Control (CDC) Class C (OR=1.83, p=0.04) were significantly more likely to report pain. For all subjects, only 52% of caregivers recognized their child's pain and just 22% were aware that pain affected their child's daily activities. The odds of reported pain in HIV increased with higher symptom severity for generalized anxiety (OR=1.14, p=0.03), major depression (OR=1.15, p=0.03), and dysthymia (OR=1.18, p=0.01). This study underscores the importance of queries concerning pain and emotional stressors in the care of HIV and uninfected children exposed to HIV individuals. The discordance between patient and caregiver reports of pain and its impact on activities of daily living highlights that pain in children is under-recognized and therefore potentially under-treated.

Increased incidence of asthma in HIV-infected children treated with highly active antiretroviral therapy in the National Institutes of Health Women and Infants Transmission Study.

BACKGROUND: Immunoreconstitution of HIV(+) patients after treatment with highly active antiretroviral therapy (HAART) appears to provoke inflammatory diseases. OBJECTIVE: We sought to determine whether HIV(+) children receiving HAART (HIV(+) HAART(+)) have a higher incidence of asthma than HIV(+) children not receiving HAART (HIV(+) HAART(-)). METHODS: Two thousand six hundred sixty-four children (193 HIV(+) and 2471 HIV(-) children) born to HIV(+) women were evaluated for the incidence and prevalence of asthma (ie, asthma medication use) and change of CD4(+) T-cell percentage with time. RESULTS: The HIV(+) HAART(+) children had higher CD4(+) T-cell percentages, lower CD8(+) T-cell percentages, and lower viral burdens than the HIV(+) HAART(-) children (P < or = .05 to P < or = .01). The cumulative incidence of asthma medication use in HIV(+) HAART(+) children at 13.5 years increased to 33.5% versus 11.5% in HIV(+) HAART(-) children (hazard ratio, 3.34; P = .01) and was equal to that in the HIV(-) children. In children born before the HAART era, the prevalence of asthma medication use for HIV(+) HAART(+) children at 11 years of age was 10.4% versus 3.8% for HIV(+) HAART(-) children (odds ratio, 3.38; P = .02) and was equal to that of the HIV(-) children. The rate of change of CD4(+) T cells around the time of first asthma medication for HIV(+) HAART(+) versus HIV(+) HAART(-) children was 0.81%/y versus -1.43%/y (P = .01). CONCLUSION: The increased incidence of asthma in HIV(+) HAART(+) children might be driven by immunoreconstitution of CD4(+) T cells.

Long-term safety and efficacy of a once-daily regimen of emtricitabine, didanosine, and efavirenz in HIV-infected, therapy-naive children and adolescents: Pediatric AIDS Clinical Trials Group Protocol P1021.

BACKGROUND: Compliance with complex antiretroviral therapy regimens is a problem for HIV-1-infected children and their families. Simple, safe, and effective regimens are important for long-term therapeutic success. METHODS: A novel, once-daily dosing regimen of 3 antiretroviral drugs, emtricitabine, didanosine, and efavirenz, was tested in 37 therapy-naive HIV-infected children and adolescents between 3 and 21 years of age (inclusive). Subjects were followed for > or = 96 weeks on an intention-to-treat basis. Signs, symptoms, plasma HIV-1 RNA viral load, CD4 counts, and safety laboratories were followed regularly. End points were the proportion of subjects with plasma HIV < 400 or 50 HIV copies per mL and safety and tolerability of the regimen. RESULTS: Thirty-seven subjects enrolled at 16 sites. Two subjects with rashes during the first 2 weeks of therapy were the only adverse events leading to study-drug discontinuation. Other early (before protocol-scheduled conclusion) study discontinuations included 3 viral failures on treatment and 5 patients who stopped therapy for apparently nonmedical reasons. Possible drug-related adverse events included 1 grade 4 low-glucose and 5 varied grade 3 events. There were no deaths. Virologic outcomes demonstrated that 32 (85%) of 37 subjects achieved viral suppression to < 400 RNA copies per mL, and 26 (72%) of 37 subjects maintained sustained suppression at < 50 copies per mL through week 96. The median baseline CD4 count was 310 per microL (17%), which increased at week 96 by a median of +329 cells per microL (by +18% CD4). Pharmacokinetic results were as predicted for emtricitabine, didanosine, and efavirenz capsules, whereas efavirenz concentrations in children receiving efavirenz oral solution were lower than anticipated, requiring a dose escalation after the planned assessment point. CONCLUSIONS: A once-daily regimen of emtricitabine, didanosine, and efavirenz proved to be safe and tolerable and demonstrated good immunologic and virologic efficacy in this 2-year study.