Safety and immunogenicity of early measles vaccination in children born to HIV-infected mothers in the United States: results of Pediatric AIDS Clinical Trials Group (PACTG) protocol 225.

UNLABELLED: BACKGROUND.: ACTG (Pediatric AIDS Clinical Trials Group) 225, a multicenter, randomized, open-label trial in the United States evaluated reactogenicity and immunogenicity of 2 vaccination regimens: monovalent measles vaccine (Attenuvax) at 6 months of age and measles, mumps, and rubella, live attenuated (MMRII) vaccine at 12 months of age (2D), or only MMRII at 12 months of age (1D) in human immunodeficiency virus-infected (HIV-infected) (POS) and uninfected (NEG) children in the pre-highly active antiretroviral therapy (pre-HAART) period. METHODS: Plaque-reduction neutralization (PRN) of measles-neutralizing antibody titers were evaluated at study weeks 0, 6, 26, 32, 52, and 130 (∼3 years of age). RESULTS: The 110 subjects included: 65 2DNEG; 30 1DNEG; 7 2DPOS and 8 1DPOS. Vaccinations (n=175) were associated with no adverse experiences >Grade 2 except for Grade 3 fever (n=2, 1 1DPOS and 1 1DNEG). Six weeks after Attenuvax, all 2DPOS subjects (7/7) seroresponded (PRN titers ≥120 mIU/mL) with median titers significantly exceeding 2DNEG titers (2115 vs 628 mIU/mL, respectively; P=.023). At ∼3 years of age, 67% 1DPOS (4/6) and 83% 2DPOS (4/5) subjects maintained titers ≥120 mIU/mL. Prevaccination titers ≥25 mIU/mL among 2DNEG subjects correlated inversely with the likelihood of achieving titers ≥120 mIU/mL (56% vs 90%; P=.004). CONCLUSIONS: Among HIV-infected children pre-HAART, Attenuvax at 6 months was well tolerated and immunogenic. These data support the current World Health Organization (WHO) recommendation to administer a first dose of measles vaccine at 6 months of age to HIV-infected children.

Intramedullary schistosomiasis presenting in an adolescent with prolonged intermittent back pain.

A 14-year-old boy traveling from Guinea presented with a 2-month history of stable lower back pain. His neurologic examination was significant only for mild weakness in the distal lower extremities. He manifested peripheral eosinophilia, and magnetic resonance imagining revealed enlargement of the caudal aspect of the spinal cord and conus. A presumptive diagnosis of spinal schistosomiasis was rendered, and appropriate medication was administered before obtaining positive serology results. The patient's signs rapidly resolved. Spinal schistosomiasis should be considered in the differential diagnosis of any child with back pain and an appropriate travel history.

Natural history of HIV infected pediatric long-term or slow progressor population after the first decade of life.

BACKGROUND: Perinatally infected long-term nonprogressors/slow progressors represent a select group of individuals. There is very limited information on this group of children beyond the first decade of life. A group of HIV-infected long-term nonprogressor/slow progressor children was studied. METHODS: We enrolled 20 HIV-infected adolescents who were receiving no or minimal therapy (defined as single or dual nucleoside therapy) before the age of 10 years and who had maintained CD4 counts above 25% for the first decade of life. We analyzed immunologic and virologic characteristics. Thymic receptor excision circles (TREC) were measured on stored frozen peripheral blood mononuclear cells. CD4 count, viral load and other pertinent information including race and age were obtained from individual medical records. RESULTS: Nine of the 20 patients recruited were noted to have developed falling CD4 counts at or around puberty, whereas the other 11 remained stable. There was no difference in TREC values or HIV RNA values before or after puberty between the 2 groups of patients. Those who remained stable, in terms of maintaining CD4 T cells as a group had falling viral loads with age. Those whose CD4 values declined after puberty had viral loads that did not decrease with age. CONCLUSION: A select group of patients who never received HAART during their first decade of life will continue to maintain good CD4 associated with declining HIV RNA values. Thymic output is not predictive of those that don't maintain CD4 T cells.

Correlation between HIV-Specific CD8 cell production of interferon- gamma and plasma levels of HIV RNA in perinatally infected pediatric populations.

BACKGROUND: CD8 cell responses to human immunodeficiency virus (HIV) have been correlated with virus control in adults, and this study outcome has been controversial. Attempts to establish the same correlation in small numbers of children have also been made, with similar controversy resulting. METHODS: A total of 110 perinatally infected children were studied. Nine of the children (mean age, 1.9 years vs. 11.8 years for the remaining 101 children) received treatment with antiretrovirals within the first 3 months of life. CD4 cell and HIV RNA levels were measured. Production of interferon- gamma after exposure to recombinant vaccinia vectors was measured by enzyme-linked immunospot (ELISPOT) assay. RESULTS: Responses to Pol and Gag antigens exceeded those to Nef and Env antigens, with responses significantly approximated by a quadratic function for which peak responses occurred at plasma HIV RNA levels of 103-104 HIV RNA copies/mL. Children who are treated early in life with highly active antiretroviral therapy have fewer total responses of ELISPOT-forming cells to HIV antigens than do children who are treated later in life.

Recombinant glycoprotein vaccines for human immunodeficiency virus-infected children and their effects on viral quasispecies.

In individuals infected with human immunodeficiency virus type 1 (HIV-1), specific immunity is associated with a more diverse viral repertoire and slower disease progression. Attempts to enhance antiviral immunity with therapeutic vaccination have shown that recombinant glycoprotein (RGP) vaccines are safe, well tolerated, and immunogenic, but the effect of RGP vaccines on the viral repertoire is unknown. We evaluated diversification of the viral envelope in 12 HIV-infected children who received placebo or RGP vaccines. At baseline, 11 of 12 patients had multiple viral variants. On follow-up 6 months later, children who had a strong vaccine-associated lymphoproliferative immune response showed less viral diversification than those in whom the immune response was weak or absent. These results suggest that the immune response elicited by RGP vaccines does not exert a significant selection pressure on the viral quasispecies and therefore may not be helpful in changing the course of the disease.

Immunoreconstitution in children receiving highly active antiretroviral therapy depends on the CD4 cell percentage at baseline.

The effect of highly active antiretroviral therapy (HAART) in 85 children infected with human immunodeficiency virus type 1 (HIV-1) was compared retrospectively among Centers for Disease Control and Prevention (CDC) immunologic groups 1-3. The duration of HAART did not vary significantly among the immunologic groups (median, 39.07 months). The CD4 cell percentage increased in 39.1%, 58.3%, and 90% of patients in CDC groups 1-3, respectively (P <.001). HAART resulted in the suppression of HIV-1 below detectable levels in 34.8%, 25%, and 32% of patients in the 3 CDC groups, respectively, and in a frequent switch from syncytium-inducing to nonsyncytium-inducing virus. Thymic excision circles increased in a subset of patients with increases in CD4 cell percentage independently of HIV RNA level. The results support the option of delaying HAART in early asymptomatic HIV-1 disease in children and the use of other markers of disease progression, in addition to virus load.