Safety and immunogenicity of a quadrivalent human papillomavirus (types 6, 11, 16, and 18) vaccine in HIV-infected children 7 to 12 years old.

BACKGROUND: Quadrivalent human papillomavirus vaccine (QHPV) is > 95% effective in preventing infection with vaccine-type human papillomavirus. The safety and immunogenicity of QHPV are unknown in HIV-infected children. METHODS: HIV-infected children (N = 126)-age > 7 to < 12 years, with a CD4% ≥ 15-and on stable antiretroviral therapy if CD4% was < 25-were blindly assigned to receive a dose of QHPV or placebo (3:1 ratio) at 0, 8, and 24 weeks. Adverse events were evaluated after each dose. Serum antibody against QHPV antigens was measured by a competitive Luminex immunoassay 1 month after the third QHPV dose. RESULTS: The safety profile of QHPV was similar in the 2 study arms and to that previously reported for QHPV recipients. QHPV did not alter the CD4% or plasma HIV RNA. Seroconversion to all 4 antigens occurred in > 96% of QHPV recipients and in no placebo recipients. Geometric mean titer was > 27 to 262 times greater than the seropositivity cutoff value, depending on the antigen, but was 30%-50% lower against types 6 and 18 than those of age-similar historical controls. CONCLUSIONS: QHPV was safe and immunogenic in this cohort of HIV-infected children. Efficacy trials are warranted.

Predictors of immunologic long-term nonprogression in HIV-infected children: implications for initiating therapy.

BACKGROUND: Early markers that predict immunologic long-term nonprogression in infants with perinatally acquired HIV infection might assist in subsequent antiretroviral treatment decisions. OBJECTIVES: We sought to identify early markers of immunologic long-term HIV disease nonprogression. METHODS: We analyzed immunologic and virologic characteristics at 1 and 2 months of age in HIV-infected children who were enrolled in the Women and Infants Transmission Study and born before 1995, comparing immunologic long-term nonprogressors (ILTNPs; n = 10) with non-ILTNPs (n = 127). ILTNPs were children who survived to 8 years or older with CD4 percentages of 25% or greater and counts of 500 cells/mm 3 or more without receiving highly active antiretroviral therapy. Non-ILTNPs were defined as all other HIV-infected children. Receiver operating characteristic curve analysis was used to assess combined sensitivity and specificity for each of these characteristics and to determine potential threshold values to discriminate between ILTNPs and non-ILTNPs. RESULTS: Characteristics in the first 2 months of life associated with ILTNP status in univariate analysis included higher CD4 percentages, lower CD8 + percentages, lower CD8 + HLA-DR + percentages, and lower HIV-1 RNA PCR values. In receiver operating characteristic analysis CD8 + HLA-DR + percentage had the best combined sensitivity and specificity for discriminating between ILTNPs and non-ILTNPs. CD8 + HLA-DR + percentages of 5% or less predicted ILTNP status with 80% sensitivity and 80% specificity. In multivariate analysis CD8 + HLA-DR+ percentage of 5% or less remained a significant predictor of ILTNP status after adjusting for CD3 + CD4 + percentage and HIV-1 RNA PCR value (odds ratio, 15.4; 95% CI, 1.9-124.7). CONCLUSION: CD8 + HLA-DR + T-lymphocyte percentage of less than 5% at 1 to 2 months of age might be predictive for ILTNP status but should not be used at this time to make treatment-deferral decisions. Immune activation in HIV-infected infants might herald more disease progression. Further study of the use of this subpopulation in early infancy to predict ILTNP status is warranted.

Morbidity and mortality during the first two years of life among uninfected children born to human immunodeficiency virus type 1-infected women: the women and infants transmission study.

OBJECTIVE: We evaluated morbidity and mortality during the first 2 years of life among children born to human immunodeficiency virus-(HIV) type 1-infected women enrolled in the Women and Infants Transmission Study (WITS) during an 11-year period (1990-2001). DESIGN AND METHODS: As part of WITS, evaluations were performed at birth and at 1, 2, 4, 6, 9, 12, 18 and 24 months of age. Growth, hospitalization and the incidence of clinical disease were assessed regularly. RESULTS: Data regarding 1118 children born to HIV-infected women (955 HIV-uninfected children and 163 HIV-infected children) were analyzed. Fewer changes in the caretaker of the child and fewer in utero exposures to drugs, tobacco and alcohol occurred in the latter periods of the study (all P values for time trend analyses <0.01). The percentages of HIV-uninfected children with poor weight gain (44 of 767; 5.7%), short stature (32 of 703; 4.5%) and wasting (27 of 792; 3.4%) were higher than expected for the general population. Two or more changes in caretaker were associated with all growth deficiencies except wasting, and fetal exposure to tobacco was associated with height abnormalities. Anemia was common and was associated with receipt of zidovudine prophylaxis. Morbidity and mortality decreased during the study period. For the uninfected children, a decrease in class A events (Kaplan-Meier rates: group 1, 22.3%; group 2, 6.8%; group 3, 4.2%; P < 0.001) and class C events and death (Kaplan- Meier event rates: group 1, 2.0%; group 2, 1.7%; group 3, 0.2%; P = 0.062) during the first 2 years of life account for the differences in the curves over time. CONCLUSIONS: During an 11-year period, morbidity and mortality during the first 24 months of life decreased substantially for children born to HIV-infected women.