Long-term nonprogression of HIV infection in children: evaluation of the ANRS prospective French Pediatric Cohort.
ABSTRACT 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.
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.
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.
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.
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ABSTRACT: The pediatrician plays a key role in the prevention of mother-to-child transmission of HIV-1 infection. For infants born to women with HIV-1 infection identified during pregnancy, the pediatrician ensures that antiretroviral prophylaxis is provided to the infant to decrease the risk of acquiring HIV-1 infection and promotes avoidance of postnatal HIV-1 transmission by advising HIV-1-infected women not to breastfeed. The pediatrician should perform HIV-1 antibody testing for infants born to women whose HIV-1 infection status was not determined during pregnancy or labor. For HIV-1-exposed infants, the pediatrician monitors the infant for early determination of HIV-1 infection status and for possible short- and long-term toxicity from antiretroviral exposures. Provision of chemoprophylaxis for Pneumocystis jiroveci pneumonia and support of families living with HIV-1 by providing counseling to parents or caregivers are also important components of care.PEDIATRICS 02/2009; 123(1):175-87. DOI:10.1542/peds.2008-3076 · 5.30 Impact Factor
- Medicina Clínica 04/2009; 132(13):505-506. DOI:10.1016/j.medcli.2008.12.021 · 1.25 Impact Factor
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ABSTRACT: Characterization of HIV-1 from slow progressors is important to facilitate vaccine and antiviral drug development. To identify virus attenuations that may contribute to slower rates of disease progression, the full-length viral genomes from primary isolates of six slow progressing HIV-positive children were sequenced. Proviral DNA was extracted from cocultured peripheral blood mononuclear cells and used to PCR amplify, sequence, and extensively analyze the near full-length genomes and LTR regions. All primary HIV-1 isolates were HIV-1 subtype C throughout their genome, and amino acid (AA) sequence analysis revealed open reading frames for all genes. However, all isolates had at least one unusual gene/protein. For example, isolate LT5 had a 2AA insertion in the Vpr mitochondriotoxic domain. Isolate LT21 contained an additional 5AA in the C-terminus of tat exon 2, while integrase in isolate LT39 had an additional 4AA at the C-terminus. Rev from isolates LT45 and LT46 did not have the characteristic subtype C 16AA truncation, and in addition, had a further 3AA. Furthermore, altered functional domains were noted in several isolates, such as the cAMP-dependent kinase PKA phosphorylation site in Nef (LT5), a Vpr mutation involved in decreased proapoptotic activity (all isolates), and the Nef ExxxLL motif involved in the interaction with AP-1 and AP-2 (LT46). The slower HIV-1 disease progression in these six children may be attributed to altered protein functions. For example, LT46 Nef is unable to bind AP-1 and AP-2 and therefore is inactive on CD4 endocytosis. The biological relevance of these findings requires further investigation.AIDS research and human retroviruses 11/2009; 25(11):1141-8. DOI:10.1089/aid.2009.0080 · 2.46 Impact Factor