Nancy A. Wade

Mitochondrial damage and DNA depletion in cord blood and umbilical cord from infants exposed in utero to Combivir.

Objective: Although most uninfected infants born to women infected with HIV-1 show no clinical evidence of mitochondrial compromise, mitochondrial dysfunction has been reported in children born to women receiving zidovudine and/or lamivudine during pregnancy. In this pilot study we examined mitochondrial integrity in HIV-1-uninfected infants born to HIV-1-infected women receiving Combivir during pregnancy. Design: Samples of umbilical cord and cord blood were obtained from HIV-1-uninfected infants born to either HIV-1-infected women receiving Combivir therapy during pregnancy (n = 10) or HIV-1-uninfected women (n = 9). Methods: Mitochondrial morphological integrity was examined in umbilical cords (n = 16) by electron microscopy and mtDNA quantity was determined in DNA from cord blood (n = 18) and umbilical cord (n = 18) by PCR-chemiluminescence immunoassay detection. Results: In umbilical cords from six of nine infants born to HIV-1-infected mothers taking Combivir moderate to severe mitochondrial morphological damage was observed (P = 0.011), while none of seven unexposed infants showed similar damage. Compared to unexposed infants, statistically significant mtDNA depletion was observed in umbilical cord (P = 0.006) and cord blood (P = 0.003) from drug-exposed infants. Conclusions: A cohort of HIV-1-uninfected Combivir-exposed infants with no clinical symptoms showed morphological and molecular evidence of mitochondrial damage.

Decline in perinatal HIV transmission in New York State (1997-2000).

Background:Perinatal HIV transmission has declined significantly in New York State (NYS) since implementation of a 3-part regimen of zidovudine prophylaxis in the antenatal, intrapartum, and newborn periods. This study describes the factors associated with perinatal transmission in NYS from 1997 to 2000, the first 4 years of NYS’s comprehensive program in which all HIV-exposed newborns were identified through universal HIV testing of newborns. Methods:This population-based observational study included all HIV-exposed newborns whose infection status was known and their mothers identified in NYS through the universal Newborn HIV Screening Program (NSP) from February 1997 to December 2000. Antepartum, intrapartum, newborn, and pediatric medical records of HIV-positive mothers/infants were reviewed for history of prenatal care, antiretroviral therapy (ART), and infant infection status. Risks associated with perinatal HIV transmission were examined. Results:Perinatal HIV transmission declined significantly from 11.0% in 1997 to 3.7% in 2000 (P < 0.05). Prenatal ART was associated with a decline in perinatal HIV transmission both for monotherapy (5.8%, relative risk [RR] = 0.3, 95% confidence interval: 0.2%–0.5%) and combination therapy [2.4%, RR = 0.1, 95% confidence interval: 0.1%–0.2%) compared with no prenatal antiretroviral prophylaxis (P < 0.05). Conclusions:Public health policies to improve access to care for pregnant women and advances in clinical care, including receipt of appropriate preventive therapies, have contributed to declines in perinatal HIV transmission in NYS.

Intravenous immune globulin treatment of pulmonary exacerbations in cystic fibrosis

The effect of intravenously administered immune globulin (IVIG) on patients with cystic fibrosis with an acute exacerbation of pulmonary infection was evaluated in a double-blind study. Patients at least 12 years of age, with chronic respiratory tract colonization with Pseudomonas aeruginosa and hospitalized with a reduction in pulmonary function, were randomly assigned to receive 20% dextrose (control subjects: n = 8) or 100 mg/kg IVIG (Gamimune) (experimental subjects: n = 8) on days 1, 2, and 3; all patients received intravenous antibiotics and chest physiotherapy. There were no differences between groups on admission; patients had moderate to severe disease as measured by Shwachman-Kulczycki scores and pulmonary function tests. Both groups improved clinically. The IVIG treatment was associated with significant increases in forced vital capacity and forced expiratory volume in 1 second (p less than 0.01) and with greater percent improvement in forced expiratory volume and forced expiratory flow (25% to 75%) (p less than 0.05). There was no effect on length of hospitalization (18.3 +/- 11.9 days control vs 17.6 +/- 6.5 experimental). The C3 level was decreased at discharge in IVIG-treated patients; circulating immune complex levels were unchanged. One patient in each group experienced side effects. There were no differences on follow-up at 6 weeks. We conclude that IVIG infusion early in treatment for pulmonary exacerbations in cystic fibrosis patients with moderate to severe disease may be associated with greater improvement in pulmonary function than standard treatment alone.

Pharmacokinetics and Safety of Stavudine in HIV-Infected Pregnant Women and Their Infants: Pediatric AIDS Clinical Trials Group Protocol 332

This study evaluates the safety, tolerance, and pharmacokinetics of stavudine (d4T) in human immunodeficiency virus (HIV)-infected zidovudine (ZDV)-intolerant/refusing pregnant women and of single-dose d4T in their infants. Women received d4T and lamivudine (3TC) from enrollment until labor. During labor, women received oral 3TC and either intravenous or oral d4T. Infants received ZDV and 3TC for 6 weeks and a single dose of oral d4T at weeks 1 and 6. Mean maternal antenatal d4T pharmacokinetics (terminal plasma half-life [T1/2], 83.5+/-16.8 min; area under the plasma-concentration time curve [AUC0-infinity), 81.6+/-22.0 microg.min/mL; n=6) were not significantly different from those during labor (T(1/2), 87.3+/-24.7 min; AUC0-infinity, 88.1+/-16.6 microg.min/mL; n=6). Umbilical-cord and maternal plasma concentrations were not significantly different from one another. The oral clearance of d4T in infants was significantly greater at week 6 versus week 1 (6.8+/-1.0 vs. 5.6+/-1.2 mL/min/kg). There were no toxicities, in women or infants, that required discontinuation or modification of the study drug. No infants had positive HIV viral diagnostic tests. d4T with or without 3TC is a potential alternative to ZDV for HIV-infected pregnant women.

Immunologic considerations in pediatric HIV infection

Summary The pervasive effect of HIV infection on the immune system requires that the clinician be alert to the variety of immunologic abnormalities that can result from this disease. The tests described in this section provide guidelines for testing the HIV-infected child. Additional information on immunologic evaluations in the child with indeterminate HIV infection status can be found in the article on ambulatory care.

Myeloradiculopathy associated with wasp sting

A 12-year-old girl developed a reversible myeloradiculopathy 1 week after a wasp sting. Delayed neurologic hypersensitivity reactions to Hymenopteran stings occur primarily in adults. Reactions involving both the peripheral and central nervous systems are extremely rare and have never been reported in a child. The mechanisms underlying this uncommon reaction may be related to age-dependent differences in immunologic responses.