Epidemiology of new cases of HIV-1 infection in children referred to the metropolitan pediatric hospital in Washington, DC.

Between 2000 and 2005, 84 HIV-infected children were referred to Children's National Medical Center; 28 were born to immigrant mothers, 89% of whom were of African descent. Rates of antiretroviral prophylaxis were low regardless of maternal origin. Nonimmigrant mothers (30.4%) used illicit drugs (P < 0.001), and 50% of immigrant mothers breast-fed their children (P < 0.001). These data can guide intervention strategies.

Hospitalization trends among children and youths with perinatal human immunodeficiency virus infection, 1990-2002.

BACKGROUND: Major improvements in disease progression among HIV-infected children have followed the adoption of combination antiretroviral therapy. METHODS: We examined trends in hospitalization rates between 1990-2002 among 3,927 children/youths with perinatal HIV infection, ranging in age from newborn to 21 years. We used Poisson regression to test for trends in hospitalization rates by age and year; binomial regression to test for trends in intensive care unit (ICU) admissions and hospitalization at least once and more than once, by age and year; and multivariate logistic regression to examine factors associated with hospitalization, ICU admission, and hospitalization longer than 10 days. RESULTS: Statistically significant downward trends in hospitalization rates and multiple hospitalizations were observed in all age groups from 1990-2002. The proportion of HIV-infected children/youths who were hospitalized at least once declined from 30.4% in 1990 to 12.9% in 2002, with a steady decline occurring after 1996, when the U.S. Public Health Service issued guidelines recommending triple-drug antiretroviral therapy (triple therapy) for HIV-infected children. ICU admissions declined significantly in all age groups except among children younger than 2 years. Logistic regression results indicated that black and Hispanic children/youths were significantly more likely to be hospitalized than white children/youths and that children/youths receiving triple therapy were significantly more likely to be hospitalized than therapy-naive children; the latter association was not observed among children monitored from 1997-2002. CONCLUSIONS: Substantial reductions in rates of hospitalization, multiple hospitalizations, and ICU admission have occurred among HIV-infected children/youths from 1990-2002, particularly after 1996, with increased use of triple therapy.

Trends in antiretroviral therapy use and survival rates for a large cohort of HIV-infected children and adolescents in the United States, 1989-2001.

BACKGROUND: In the United States, HIV-infected children and adolescents are aging and using antiretroviral (ARV) therapy for extended periods of time. OBJECTIVE: To assess trends in ARV use and long-term survival in an observational cohort of HIV-infected children and adolescents in the United States. METHODS: The Pediatric Spectrum of HIV Disease Study (PSD) is a prospective chart review of more than 2000 HIV-infected children and adolescents. Patients were included in the analysis from enrollment until last follow-up. RESULTS: Triple-ARV therapy use (for 6 months or more) increased from 27% to 66% during 1997 to 2001 (P < 0.0001, chi for trend). The proportion of patients receiving 3 or more sequential triple-therapy regimens also increased from 4% to 17% during 1997 to 2001 (P < 0.0001, chi for trend), however, and the durability of triple-therapy regimens decreased from 13 to 7 months from the first to third regimen. Survival rates for the 1997 to 2001 birth cohorts were significantly better than for the 1989 to 1993 and 1994 to 1996 cohorts (P < 0.0001). CONCLUSIONS: Survival rates in the PSD cohort have increased in association with triple-ARV therapy use. With continued changes in ARV regimens, effective modifications in ARV therapy and the sustainability of gains in survival need to be determined.

A 20-year history of childhood HIV-associated nephropathy.

In 1984, physicians in New York and Miami reported HIV-infected adult patients with heavy proteinuria and rapid progression to end-stage renal disease. These patients showed large edematous kidneys with a combination of focal segmental glomerulosclerosis (FSGS) and tubulointerstitial lesions. This renal syndrome, named HIV-associated nephropathy (HIVAN), was found predominantly in African Americans. Subsequent studies confirmed the presence of HIVAN in children, who frequently develop nephrotic syndrome in association with FSGS and/or mesangial hyperplasia with microcystic tubular dilatation. Since then, substantial progress has been made in our understanding of the etiology and pathogenesis of HIVAN. This article reviews 20 years of research into the pathogenesis of HIVAN and discusses how these concepts could be applied to the treatment of children with HIVAN. HIV-1 infection plays a direct role in the pathogenesis of childhood HIVAN, at least partially by affecting the growth and differentiation of glomerular and tubular epithelial cells and enhancing the renal recruitment of infiltrating mononuclear cells and cytokines. An up-regulation of renal heparan sulfate proteoglycans seems to play a relevant role in this process, by increasing the recruitment of heparin-binding growth factors (i.e., FGF-2), chemokines, HIV-infected cells, and viral proteins (i.e., gp120, Tat). These changes enhance the infectivity of HIV-1 in the kidney and induce injury and proliferation of intrinsic renal cells. Highly active anti-retroviral therapy (HAART) appears to be the most promising treatment to prevent the progression of childhood HIVAN. Hopefully, in the near future, better education, prevention, and treatment programs will lead to the eradication of this fatal childhood disease.

Missed opportunities for perinatal HIV prevention among HIV-exposed infants born 1996-2000, pediatric spectrum of HIV disease cohort.

OBJECTIVE: Despite dramatic reductions in perinatal human immunodeficiency virus (HIV) transmission in the United States, obstacles to perinatal HIV prevention that include lack of prenatal care; failure to test pregnant women for HIV before delivery; and lack of prenatal, intrapartum, or neonatal antiretroviral (ARV) use remain. The objective of this study was to describe trends in perinatal HIV prevention methods, perinatal transmission rates, and the contribution of missed opportunities for perinatal HIV prevention to perinatal HIV infection. METHODS: We analyzed data obtained from infant medical records on 4755 HIV-exposed singleton deliveries in 1996-2000, from 6 US sites that participate in the Centers for Disease Control and Prevention's Pediatric Spectrum of HIV Disease Project. HIV-exposed deliveries refer to deliveries in which the mother was known to have HIV infection during the pregnancy. RESULTS: Of the 4287 women with data on prenatal care, 92% had prenatal care. From 1996 to 2000, among the 3925 women with prenatal care, 92% had an HIV test before delivery; the use of prenatal zidovudine (ZDV) alone decreased from 71% to 9%, and the use of prenatal ZDV with other ARVs increased from 6% to 70%. Complete data on maternal and neonatal ARVs were available for 3284 deliveries. Perinatal HIV transmission was 3% in 1651 deliveries with prenatal ZDV in combination with other ARVs, intrapartum ZDV, and neonatal ZDV; 6% in 1111 deliveries with prenatal, intrapartum, and neonatal ZDV alone; 8% in 152 deliveries with intrapartum and neonatal ZDV alone; 14% of 73 deliveries with neonatal ZDV only started within 24 hours of birth; and 20% in 297 deliveries with no prenatal, intrapartum, and neonatal ARVs. Complete data on prenatal events were available in 328 HIV-infected and 3258 HIV-uninfected infants. A total of 56% of mothers of HIV-infected infants had missed opportunities for perinatal HIV prevention versus 16% of mothers of HIV-uninfected infants. Forty-four percent of the infected infants were born to mothers who had prenatal care, a prenatal HIV diagnosis, and documented prenatal ARV therapy. Seventeen percent of women with reported illicit drug use had no prenatal care versus 3% of women with no reported drug use. In a multivariate analysis, maternal illicit drug use was significantly associated with lack of prenatal care. In a multivariate analysis, year of infant birth and the combination of lack of maternal HIV testing before delivery and lack of prenatal antiretroviral therapies were significantly associated with perinatal HIV transmission. CONCLUSIONS: Missed opportunities for perinatal HIV prevention contributed to more than half of the cases of HIV-infected infants. Prenatal care and HIV testing before delivery are major opportunities for perinatal HIV prevention. Illicit drug use was highly associated with lack of prenatal care, and lack of HIV testing before delivery was highly associated with perinatal HIV transmission.

Increasing trend of Cesarean deliveries in HIV-infected women in the United States from 1994 to 2000.

BACKGROUND: Meta-analysis and randomized clinical trial results reported in June 1998 indicated a significant reduction in perinatal HIV transmission rates among mothers undergoing a cesarean section (C-section). OBJECTIVE: The objective of this study was to examine recent trends in and factors associated with C-section deliveries among HIV-infected women in the United States. DESIGN: A multisite pediatric medical record review of a cohort of HIV-exposed and HIV-infected infants in the Pediatric Spectrum of HIV Disease (PSD) Cohort study (n = 6467) and the national Pediatric HIV/AIDS Reporting System (HARS) (n = 8,306) was conducted. SETTING/PATIENTS: All infants born between 1994 and 2000 to HIV-positive mothers referred to the PSD study or to a Pediatric HARS hospital or clinic site were enrolled. RESULTS: The proportion of deliveries by C-section was steady at about 20% from 1994 through June 1998. From July 1998 through December 2000, this proportion increased to 44% in the PSD study and to nearly 50% in the Pediatric HARS. On analysis by multiple logistic regression, delivery of infants by C-section was associated with the release of study results (OR = 2.83), delivery in four PSD sites in reference to Texas (OR: 2.02-1.43), having private medical care reimbursement (OR = 1.62), and having maternal prenatal care (OR = 1.43). CONCLUSIONS: The PSD and Pediatric HARS data demonstrate a sharp increase in C-section rates mainly among HIV-infected women in the United States after the release of the meta-analysis and randomized clinical trial results in 1998. This finding highlights the rapid impact of study results on obstetric practice. It underscores the critical role of prenatal care in offering perinatal interventions such as scheduled C-section when indicated to reduce the likelihood of HIV transmission.