Marilyn Doyle

Congenital Cytomegalovirus Infection in Infants Infected with Human Immunodeficiency Virus Type 1

OBJECTIVES To determine the rate of in utero transmission of cytomegalovirus (CMV) in perinatally HIV-exposed infants and to determine whether coinfection with CMV in early life affects outcome. METHODS Infants born to HIV-infected women between March, 1988, and March, 1995, were evaluated (n = 206). Congenital or in utero CMV infection was defined as a positive CMV culture or shell vial assay on urine obtained in the first 3 weeks of life. HIV-infected infants either had positive serology beyond 18 months of age or, for an infant younger than 18 months, had a positive HIV PCR or HIV culture on at least two separate occasions. RESULTS There were 30 HIV-infected and 171 uninfected infants (144 who seroreverted and 27 infants with at least 2 negative HIV PCR or culture results and normal immunologic studies during the first 6 months of age). Urine culture for CMV was obtained during the first 3 weeks of life on 154 infants: 24 of 30 (80%) HIV-infected infants; and 130 of 171 (76%) HIV-uninfected infants. Overall 10 of 154 (6.5%) infants were infected with CMV: 5 of 24 (21%) HIV-infected and 5 of 130 (3.8%) HIV-uninfected infants. The rate of in utero CMV infection was significantly higher in HIV-infected infants (P = 0.008). Dually infected infants were more immunosuppressed than their CMV-negative counterparts. At 3 months of age the percentage of CD4+ T lymphocytes (P = 0.0021) and CD4:CD8 ratios (P = 0.0018) were significantly lower in the CMV-infected infants than in the CMV-uninfected infants. At 6 months of age the absolute CD4+ T lymphocyte counts (P = 0.0038), percentage of CD4+ T lymphocytes (P = 0.044) and CD4:CD8 ratios (P = 0.037) were significantly lower in the CMV-infected infants. The mean survival of HIV-infected infants who were coinfected with CMV in early life (5 in utero and 1 perinatally infected infant identified at 7 weeks) was 24.77 months. Kaplan-Meier survival analysis indicated a trend toward decreased survival in the infants who were coinfected with CMV in early life (P = 0.088). CONCLUSIONS Congenital CMV infection is more common in HIV-infected infants than in HIV-uninfected infants. Infection with CMV in early life is associated with greater immunosuppression and may be associated with a more rapid progression of HIV infection in infants.

Safety of 2 recombinant human immunodeficiency virus type 1 (HIV-1) envelope vaccines in neonates born to HIV-1-infected women.

To determine the safety of 2 candidate vaccines against human immunodeficiency virus type 1 (HIV-1), a randomized, placebo-controlled, multicenter trial compared low, medium, and high doses of the vaccines or an adjuvant among infants born to HIV-infected women. No local or systemic reactions of grade 2 or greater were reported 48 h after the subjects underwent immunization. Grade 3 or 4 chemistry toxicities occurred in 5 (3%) and grade 3 or 4 hematologic toxicities in 17 (11%) of 154 vaccinated subjects (not significantly different from 29 adjuvant recipients). CD4(+) cell percentages of < or = 20% occurred at least once in 9 vaccinated subjects and 1 control subject. Sustained CD4(+) cell percentages of < or = 20% occurred in 4 HIV-infected children. Fourteen infants (8%) were confirmed to be HIV-infected; median CD4(+) cell counts among these children were 2074, 1674, 1584, and 821 cells/mm(3) at birth and weeks 24, 52, and 104, respectively. Thus, both vaccines were safe and well tolerated in neonates, and there was no evidence of accelerated immunologic decline in HIV-infected infants.

Growth hormone improves protein catabolism and growth in prepubertal children with HIV infection

Introduction  Poor linear growth and weight loss are well documented in children with human immunodeficiency virus (HIV) infection and past studies in adults and children have reported that loss of lean tissue mass (LTM) associated with accelerated rates of protein catabolism. We undertook this study to test the hypothesis that human recombinant GH would improve linear height in HIV‐infected children. Our second goal was to determine if GH could reverse protein catabolism in HIV‐infected children.

Protease inhibitor therapy improves protein catabolism in prepubertal children with HIV infection

UNLABELLED Past studies in adults have reported that loss of lean tissue mass (LTM) is associated with accelerated rates of protein catabolism. To date, studies of protein kinetics from pediatric patients infected by HIV have not been published; however, poor linear growth and weight loss are well-documented. The first aim of this study was to test the hypothesis that protein catabolism is high in pediatric patients with HIV. Protease inhibitors (PI) have proven to be effective therapy for pediatric HIV patients. One action of these drugs is that of lowering the viral burden, and several studies suggest that these drugs result in increased growth and weight velocity. Our second aim was to determine whether PI therapy improves protein catabolism. METHODS We studied eight children infected with HIV (ages 2.9-6.2 years, Tanner stage I, CD4 counts 100,000-300,000, 5 F/3 M) and eight healthy age- and gender-matched controls. Measures of protein turnover were conducted using the stable isotope [1-(13C)]leucine. Body composition was measured by dual X-ray absorptiometry (DXA) scan for determination of LTM, and indirect calorimetry for measurement of resting energy expenditure. Children with HIV infection were studied at baseline and after 6 weeks of PI therapy; control children were studied only once. RESULTS Protein catabolism, represented as leucine rate of appearance (Ra) in the fasted state, was higher in the HIV-infected children at baseline compared to control children. After 6 weeks of PI therapy, leucine Ra decreased, but not to the range found in control children. Leucine Ra correlated with viral burden. LTM significantly improved in all patients. CONCLUSION These results suggest that similar to HIV-infected adults, HIV-infected children have higher than normal protein catabolism. Furthermore, our measures suggest that short-term PI therapy results in improved protein catabolism and LTM.

Mother-to-child transmission of the human immunodeficiency virus in Texas

Background. The Pediatric Spectrum of HIV Diseases (PSD) project has been collecting data on HIV-exposed children in Texas since 1989. These data have now been analyzed to describe mother-to-child transmission in Texas and to provide much needed information on the magnitude of the pediatric HIV epidemic in the state. Methods. We examined trends in the numbers of perinatally exposed children and perinatally acquired cases of HIV in the Texas PSD cohort. We calculated transmission rates and relative risks for 656 children born from January, 1995, to July, 1998, that received all or part of the ACTG 076 regimen. Results. Only a small proportion (38%) of pairs of an HIV-infected mother and her HIV-exposed child received the full AIDS Clinical Trial Group 076 (ACTG 076) regimen; only 73% of the mothers received at least some prenatal care. In recent years, however, the numbers of perinatally exposed children and perinatally acquired cases of HIV have decreased in Texas. Univariate analyses showed that a reduction in the vertical transmission of HIV was associated with receipt of a full ACTG 076 regimen, receipt of a partial ACTG 076 regimen and residence in Dallas County. Conclusions. Findings identify a gap in meeting the health care needs of pregnant HIV-infected women and suggest missed opportunities to prevent mother-to-child transmission of HIV. At the same time this study confirms progress in prevention efforts to reduce mother-to-child transmission of HIV in Texas.

RSV Infection among HIV-exposed infants: Is RSV-IGIV indicated?|[dagger]| 807

Introduction: The risk of severe infection with RSV in HIV-infected infants is not known. Therefore, it is unclear whether HIV-infected infants should be prophylaxed with RSV-IGIV. The purpose of this study was to determine the incidence of hospitalization for RSV and the severity of RSV illness among our HIV-exposed population.

Early Zidovudine plus Lamivudine Therapy of HIV Infected Asymptomatic Infants† 847

Although treatment with a combination of antiretroviral agents is the recommended therapy for HIV infected symptomatic children, little data are available on the effects of early combined antiretroviral therapy in asymptomatic infants. We report viral load and lymphocyte subset data obtained before and during 180 days of treatment with zidovudine and lamivudine for 6 infants. Standard clinical laboratory procedures were used to obtain viral and immunologic data.