Marukh Bamji

Distinct Risk Factors for Intrauterine and Intrapartum Human Immunodeficiency Virus Transmission and Consequences for Disease Progression in Infected Children

Predictors and prognosis of intrauterine and intrapartum human immunodeficiency virus (HIV) transmission were investigated among 432 children of HIV-infected women in the Perinatal AIDS Collaborative Transmission Study. Timing of transmission was inferred from polymerase chain reaction or viral culture within 2 days of birth. Proportions of infections due to intrauterine transmission were similar among women using (29%) or not using zidovudine (30%). Preterm delivery was strongly associated with intrapartum transmission (relative risk, 3.7; 95% confidence interval [CI], 2.2-6.1), particularly among infants delivered longer after membrane rupture, but was not associated with intrauterine transmission. Progression to AIDS or death increased 2.5-fold (95% CI, 1.1-5.8) among intrauterine infected children, adjusting for preterm delivery, and maternal CD4 cell count. Early transmission appears unlikely to explain instances of zidovudine failure. Preterm infants may be more vulnerable to HIV acquisition at delivery, especially if membrane rupture is prolonged. Intrauterine infection does not appear to increase risk of preterm delivery.

Effect of Bimonthly Supplementation With Oral Cholecalciferol on Serum 25-Hydroxyvitamin D Concentrations in HIV-Infected Children and Adolescents

OBJECTIVE. Vitamin D insufficiency occurs commonly in HIV-infected youth in the United States. In light of the importance of vitamin D for skeletal and nonskeletal health, including innate immunity, developing methods for improving vitamin D status in HIV-infected children and adolescents is an important area of clinical research. The objective of this study was to evaluate the effect of administration of oral cholecalciferol, 100000 IU every 2 months, and 1 g/day calcium on serum 25-hydroxyvitamin D concentrations, serum and urine calcium, and HIV disease progression during a 12-month period. METHODS. HIV-infected children and adolescents who were aged 6 to 16 years were randomly assigned to receive vitamin D (100000 IU bimonthly) and calcium (1 g/day; n = 29) or double placebo (n = 27). Serum 25-hydroxyvitamin D concentrations as measured by radioimmunoassay, albumin-corrected calcium concentrations, and spot urinary calcium-creatinine ratios were determined monthly. RESULTS. No abnormalities in serum calcium concentration were observed. One participant who received placebo developed hypercalciuria. No group differences were seen in the change in CD4 count or CD4% or viral load during 12 months. The overall mean monthly serum 25-hydroxyvitamin D concentrations were higher in the group that received vitamin D and calcium than in the placebo group, as was the monthly serum 25-hydroxyvitamin D area under the curve. After completing 12 months of study, 2 (6.7%) participants in the group that received vitamin D and calcium had a trough serum 25-hydroxyvitamin D concentration <20 ng/mL compared with 14 (50%) in the placebo group. Twelve (44.4%) in the group that received vitamin D and calcium had a trough serum 25-hydroxyvitamin D concentration of ≥30 ng/mL compared with 3 (11.1%) in the placebo group. CONCLUSIONS. Administration of oral cholecalciferol to HIV-infected children and adolescents at a dosage of 100000 IU every 2 months, together with 1 g/day calcium, is safe and results in significant increases in serum 25-hydroxyvitamin D concentrations.

Effect of maternal CD4 + cell count, acquired immunodeficiency syndrome, and viral load on disease progression in infants with perinatally acquired human immunodeficiency virus type 1 infection

Among a cohort of 152 infants perinatally infected with human immunodeficiency virus type 1, and their mothers, we correlated infant outcome with material CD4+ lymphocyte count and the presence of maternal acquired immunodeficiency syndrome near delivery. In a subset of 50 mother-infant pairs, we also correlated infant outcome with maternal quantitative viral burden as measured by the nucleic acid sequence based amplification system. We found that low maternal CD4+ cell count and high viral burden were associated with decreased time to category C disease or death in infants infected with human immunodeficiency virus type 1. In a multivariate analysis, high maternal viral load and maternal acquired immunodeficiency syndrome were independently associated with shorter time to category C disease or death in infants with human immunodeficiency virus type 1 infection. High viral load in pregnant women, independent of the presence of advanced maternal disease, appears to increase the risk of rapidly progressive disease in their infected offspring.

Longitudinal changes in regional fat content in HIV-infected children and adolescents

Background:Alterations in regional fat are often reported in HIV infection. Prior studies have not distinguished between normal changes in regional fat related to sexual maturation and those due to HIV. The study aim was to compare changes in regional fat distribution in HIV-infected (HIV+) and healthy (HIV−) children and adolescents living in the United States. Methods:Serial dual energy X-ray absorptiometry was performed at baseline and two annual follow-up visits in 64 HIV+ and 147 HIV− participants aged 6–16 years. Total, leg, arm, and trunk fat masses (kg) and regional fat distribution as the percentage of total body fat (%) were compared. Results:HIV+ and HIV− participants did not differ in total fat mass, but the HIV+ group had significantly lower leg and greater arm fat and trunk fat percentage at all time points. Over time, decreases in leg fat percentage and increases in arm fat percentage were more marked among the HIV+ group. Differences between HIV+ and HIV− groups in arm and leg fat percentage remained significant when age, sex, race, height, and pubertal stage were accounted for by mixed effect modeling. Apart from prior treatment with stavudine, no differences in fat distribution were observed according to treatment or degree of immunodeficiency or viremia. Conclusion:Although no single pattern of change in regional fat distribution was uniquely associated with HIV, perinatally HIV-infected youth manifest significantly decreased leg fat and increased arm and trunk fat. These differences increase over time and may contribute to cardiovascular disease risk.

Lack of detectable human immunodeficiency virus infection in antibody-negative children born to human immunodeficiency virus-infected mothers.

More than one-half of the children born to women with human immunodeficiency virus (HIV) infection are not infected with HIV. Most of these children, although born antibody-positive, lose maternal antibody and remain asymptomatic. However, it has been unclear how many antibody-negative children of HIV-infected women may truly be infected despite the loss of passively acquired maternal antibody. One hundred nine children who lost maternal antibody after birth to HIV-infected women recruited in four United States maternal HIV transmission studies were examined for HIV infection. Polymerase chain reaction (PCR) was used to determine whether children had HIV proviral DNA in peripheral blood mononuclear cells. A total of 268 samples from 109 children were tested. Clinical status and other laboratory findings were also evaluated. The median age at last follow-up was 25 months (range, 12 to 48 months). One hundred seven (98%) children were negative by PCR on all samples tested. None (95% confidence interval, 0.0 to 1.9%) of 109 children had a repeatedly positive PCR. Two children had single positive PCR results that could not be confirmed on subsequent testing. No other laboratory or clinical findings supported HIV infection in either of these children. The loss of HIV antibody in an asymptomatic child born to an HIV-infected woman strongly suggests that the child is not infected with HIV. Single positive PCR results, particularly in the absence of other clinical or laboratory evidence of HIV infection, should not be used alone to diagnose HIV infection.

Energy balance, viral replication and growth in HIV-infected children|[dagger]| 558

The determinants of growth failure (GF) in pediatric HIV infection are uncertain. We measured dietary intake (DI), resting energy expenditure (REE), total energy expenditure (TEE), and HIV plasma RNA (viral load: VL) in 15 prepubescent HIV+ subjects with and 21 without GF, ages 4-12 years. GF was defined as 12 month growth velocity ≤5th percentile. DI was measured by 3 day food records, REE by indirect calorimetry, TEE by the doubly-labelled water technique, VL by a PCR method (Roche), and fat free mass (FFM) by dual X-ray absorptiometry. The GF+ group was older (p=0.014), had lower CD4+ lymphocyte count, and had higher VL than the GF- group. The GF+ group had lower values for height-for-age (p<0.0001), weight-for-age (p=0.001), and age-adjusted FFM (p=0.0003) than the GF-group. DI was significantly lower in GF+ children, while REE and TEE were similar in the two groups. In conclusion, decreased DI is the most important mediator of GF in HIV+ children. The mechanism underlying decreased DI may be related to viral replication. Abnormalities in REE and TEE do not appear to be factors in HIV-associated GF. Table