Relationships between HIV disease history and blood HIV-1 DNA load in perinatally infected adolescents and young adults: the ANRS-EP38-IMMIP study.

BACKGROUND: Our aim was to study the impact of lifelong human immunodeficiency virus (HIV) disease history on the current immune and virological status of perinatally infected patients reaching adulthood. We evaluated blood cell-associated HIV DNA load as an indicator of cell-associated HIV reservoirs and an independent predictor of disease progression. METHODS: The ANRS-EP38-IMMIP Study included 93 patients aged 15-24 years who were infected with HIV during the perinatal period. HIV DNA load was quantified by real-time polymerase chain reaction. RESULTS: Eighty-five percent of patients were receiving highly active antiretroviral therapy (HAART), and HIV RNA was undetectable in the plasma of 75% of these patients. The median HIV DNA load was 2.84 (interquartile range, 2.51-3.16) log(10) copies per 10(6) peripheral blood mononuclear cells. In patients with viral suppression, HIV DNA load was independently associated with cumulative HIV RNA viremia over the last 5 years. HIV DNA load was negatively correlated with CD4 cell count in patients with active replication but not in those with undetectable HIV RNA. CONCLUSIONS: In perinatally infected youths who are successfully treated, sustained viral suppression is associated with a low HIV DNA load. The absence of association between current HIV DNA load and CD4 cell counts suggests that the unique physiological characteristics of pediatric infection persist after adolescence. CLINICAL TRIALS REGISTRATION: NCT01055873.

Decreased risk of congenital cytomegalovirus infection in children born to HIV-1-infected mothers in the era of highly active antiretroviral therapy.

BACKGROUND: We evaluated the prevalence of congenital cytomegalovirus (CMV) infection before and after highly active antiretroviral therapy (HAART) availability among neonates born to human immunodeficiency virus type 1 (HIV-1)-infected mothers. We also identified maternal risk factors associated with in utero CMV transmission. METHOD: Routine screening for congenital CMV infection was performed from 1993 through 2004 in children born to HIV-1-infected mothers included in the French Perinatal Cohort (Enquête Périnatale Française). Interpretable tests on urine samples collected within the first 10 days of life were available for 4797 of the 7563 live-born infants. Prevalence was estimated for different time periods. Univariate and multivariate logistic regression analyses were performed to identify factors associated with CMV transmission in the HAART era. RESULTS: Among live-born children, the overall prevalence of CMV infection was 2.3% (95% confidence interval, 1.9%-2.8%). Prevalence was higher among HIV-1-infected neonates (10.3%; 95% confidence interval, 5.6%-17.0%) than among HIV-1-uninfected neonates (2.2%; 95% confidence interval, 1.8%-2.7%; P < .01). Among HIV-1-uninfected neonates, the prevalence of CMV infection decreased over time, from 3.5% in 1997-1998 to 1.2% in 2003-2004. Delivery period, maternal age, time at antiretroviral treatment initiation, and maternal CD4(+) cell count <200 cells/mm(3) close to delivery were independently associated with CMV infection in logistic regression analysis. The percentage of symptomatic CMV infections was 23.1% among HIV-1-infected newborns and 6.7% among HIV-1-uninfected neonates. CONCLUSIONS: The prevalence of congenital CMV infection was high and associated with high morbidity rates among HIV-1-infected neonates. Conversely, the prevalence of CMV infection decreased over time among neonates not infected with HIV-1, reaching levels similar to those observed in the general population, following the introduction and increasing use of HAART for prevention of mother-to-child HIV-1 transmission.

Long-term nonprogression of HIV infection in children: evaluation of the ANRS prospective French Pediatric Cohort.

BACKGROUND: Some children who are infected with human immunodeficiency virus type 1 (HIV-1) during the perinatal period remain asymptomatic for very long periods in the absence of antiretroviral treatment, as is the case for some adults. Our objective was to estimate the proportion of children who developed neither symptoms nor major immunological perturbations to the age of > or = 10 years in a prospective cohort of infected children who had been observed since birth. METHODS: The ongoing prospective French Pediatric Cohort includes 568 HIV-1-infected children. Here, we report the follow-up data for all 348 HIV-1-infected children who were born before 1 January 1994. Children with long-term nonprogression of infection (LTNPs) were defined as HIV-1-infected children who had been observed for at least 10 years, never received antiretroviral treatment other than zidovudine monotherapy, never developed symptoms of Centers for Disease Control and Prevention clinical category C or B, and had a CD4+ cell percentage of < 25% no more than once during follow-up. Other definitions were compared. RESULTS: The Kaplan-Meier estimate of long-term nonprogression was 2.4% (95% confidence interval, 1.1%-4.6%) at 10 years of age, and 7 children were classified as LTNPs. The Kaplan-Meier estimates decreased slightly with age, to 1.8% at 12 years of age and 1.4% at 14 years of age. Plasma HIV-1 replication rates were low (< 1000 copies RNA/mL) for 2 of the 7 LTNPs at the age of 10 years (0.6% of the total denominator). None of the routinely measured maternal or perinatal markers were significantly linked to long-term nonprogression, with the exception of the mother's Centers for Disease Control and Prevention clinical category at the time of delivery. CONCLUSIONS: Approximately 2% of children who were infected during the perinatal period displayed no immunological or clinical progression by the age of 10 years. This figure is close to that reported for adults in studies that have used similar definitions.