Behavioral impairment and cognition in Thai adolescents affected by HIV.

BACKGROUND: Cognitive and behavioral impairment are common in children living with perinatally acquired HIV (pHIV) and children exposed to HIV in utero but uninfected (HEU). METHODS: We sought to determine the prevalence of adverse behavioral symptomatology using a Thai-translated and validated version of the SNAP-IV questionnaire and assess cognitive function utilizing the Children's Color Trails Test, Delis-Kaplan Executive Function System, and the Wechsler Intelligence Scales, in our cohort of Thai adolescents (10-20 years old) with well-controlled pHIV compared to HEU and HIV-unexposed, uninfected youth. We then evaluated the interaction between HIV status, behavioral impairment, and executive function outcomes independent of demographic variables. RESULTS: After controlling for demographic factors of age and household income, adolescents with pHIV had higher inattentive symptomatology and poorer neuropsychological test scores compared to uninfected controls. Significant interactions were found between inattention and executive function across multiple neurocognitive tests. CONCLUSIONS: Behavioral impairment and poor executive functioning are present in adolescents with well-controlled pHIV compared to HIV-uninfected matched peers. The SNAP-IV questionnaire may be a useful tool to identify those with attentional impairment who may benefit from further cognitive testing in resource-limited settings.

High prevalence of lipid abnormalities among antiretroviral-naive HIV-infected Asian children with mild-to-moderate immunosuppression.

BACKGROUND: Dyslipidaemia is a common complication among HIV-infected children after antiretroviral therapy (ART); however, HIV itself can cause abnormal lipid metabolism. There is limited information of lipid profiles among Asian HIV-infected children naive to ART. METHODS: A total of 274 HIV-infected ART-naive Thai and Cambodian children aged 1-12 years with CD4% between 15% and 24% were included. Patients were fasted for ≥4 h before blood was drawn. Abnormal lipid levels were defined as triglyceride (TG)>130 mg/dl, total cholesterol (TC)>200 mg/dl, low-density lipoprotein (LDL)>130 mg/dl and high-density lipoprotein (HDL)≤40 mg/dl. RESULTS: The mean (±SD) was 76.6 (33.8) months for age and -1.3 (1.0) for weight Z-score. Mean (±SD) CD4% was 19.9 (4.8) % and HIV RNA was 4.6 (0.6) log(10) copies/ml. The median (±SD) fasting time was 13.0 (2.7) h. Mean (±SD) for lipids were 116 (62) mg/dl for TG, 139 (29) mg/dl for TC, 73 (29) mg/dl for LDL and 45 (19) mg/dl for HDL. Overall 63.9% had dyslipidaemia with hypertriglyceridaemia and hypo-HDL being the most common (28% and 45%, respectively), while 2% had hypercholesterolaemia or hyper-LDL. After adjusting for age, having HIV RNA>5 log(10) copies/ml was associated with hypo-HDL with ORs of 8.1 (95% CI 2.7-24.3). CONCLUSIONS: Up to two-thirds of ART-naive, HIV-infected Asian children with mild-to-moderate immune suppression had dyslipidaemia. Low HDL was the most common and was associated with high HIV viraemia. The long-term consequence of low HDL deserves further investigation in children.

Characteristics of lymphocyte subsets in HIV-infected, long-term nonprogressor, and healthy Asian children through 12 years of age.

BACKGROUND: There are limited data on the immune profiles of HIV-positive children compared with healthy controls, and no such data for Asian children. OBJECTIVES: To immunophenotype HIV-positive Asian children, including long-term nonprogressors (LTNPs), compared with age-matched healthy controls. METHODS: We used flow cytometry to analyze 13 lymphocyte and monocyte subsets from 222 untreated, HIV-positive children with 15% to 24% CD4(+) T cells and no AIDS-related illnesses and 142 healthy children (controls). Data were compared among age categories. Profiles from LTNPs (n = 50), defined as children ≥8 years old with CD4(+) T-cell counts ≥350 cells/mm(3), were compared with data from age-matched non-LTNPs (n = 17) and controls (n = 53). RESULTS: Compared with controls, HIV-positive children had lower values (cell count per mm(3) and percent distribution) for T(H) cells and higher values for cytotoxic T cells, with reductions in populations of naive T(H) and cytotoxic T cells, B cells, and natural killer (NK) cells. HIV-positive children had high values for activated T(H) and cytotoxic T cells. Compared with non-LTNPs, LTNPs had higher values of T(H) and cytotoxic T cells, naive and memory T-cell subsets, and B and NK cells. Surprisingly, counts of activated T(H) and cytotoxic T cells were also higher among LTNPs. LNTPs were more frequently male. CONCLUSION: Untreated, HIV-infected Asian children have immune profiles that differ from those of controls, characterized by low values for T(H) cells, naive T cells, B cells, and NK cells but high values for cytotoxic, activated T(H), and cytotoxic T cells. The higher values for activated T cells observed in LTNPs require confirmation in longitudinal studies.

Long-term survival of HIV-infected children receiving antiretroviral therapy in Thailand: a 5-year observational cohort study.

BACKGROUND: There are scarce data on the long-term survival of human immunodeficiency virus (HIV)-infected children receiving antiretroviral therapy (ART) in lower-middle income countries beyond 2 years of follow-up. METHODS: Previously untreated children who initiated ART on meeting immunological and/or clinical criteria were followed in a prospective cohort in Thailand. The probability of survival up to 5 years from initiation was estimated using Kaplan-Meier methods, and factors associated with mortality were assessed using Cox regression analyses. RESULTS: Five hundred seventy-eight children received ART; of these, 111 (19.2%) were followed since birth. At start of ART (baseline), the median age was 6.7 years, 128 children (22%) were aged <2 years, and the median CD4 cell percentage was 7%. Median duration of follow-up was 53 months; 42 children (7%) died, and 38 (7%) were lost to follow-up. Age <12 months, low CD4 cell percentage, and low weight-for-height z score at ART initiation were independently associated with mortality (P < .001). The probability of survival among infants aged <12 months at baseline was 84.3% at 1 year and 76.7% at 5 years of ART, compared with 95.7% and 94.8%, respectively, among children aged ≥1 year. Low CD4 cell percentage and wasting at baseline had a strong association with mortality among older children but weak or no association among infants. CONCLUSIONS: Children who initiated ART as infants after meeting immunological and/or clinical criteria had a high risk of mortality which persisted beyond the first year of therapy. Among older children, those with severe wasting or low CD4 cell percentage at treatment initiation were at high risk of mortality during the first 6 months of therapy. These findings support the scale-up of early HIV diagnosis and immediate treatment in infants, before advanced disease progression in older children.

Growth of human immunodeficiency virus-uninfected children exposed to perinatal zidovudine for the prevention of mother-to-child human immunodeficiency virus transmission.

BACKGROUND: Perinatal human immunodeficiency virus (HIV) prevention programs have been implemented in several countries, and many children have been or will be exposed to antiretrovirals in utero and during their first weeks of life. Although reducing substantially the number of infected children, the potential adverse consequences of these treatments on the health of HIV-uninfected children need to be assessed. OBJECTIVE: To investigate the impact of in utero and postnatal zidovudine exposure on the growth of HIV-uninfected children born to HIV-infected women. METHODS: We used data prospectively collected in 1408 live born children participating in a clinical trial comparing zidovudine regimens of different durations to prevent perinatal transmission in Thailand (PHPT-1). We used a linear mixed model to analyze the anthropometric measurements (weight for age, height for age and weight for height Z-scores) until 18 months of age according to zidovudine treatment duration (mothers, <7.5 weeks versus more; infants, 3 days versus >4 weeks). RESULTS: Children exposed in utero for >7.5 weeks had a slightly lower birth weight (Z-score difference, 0.08; P = 0.003). However, zidovudine exposure had no effect on the evolution of Z-scores from 6 weeks to 18 months of age. CONCLUSIONS: Although a longer in utero zidovudine exposure may have had a negative impact on birth weight, the magnitude of this effect was small and faded over time. Neither the total nor the postnatal duration of exposure was associated with changes in infant Z-scores from 6 weeks to 18 months of age.