Consisting of data provided by the authors to benefit the reader, the posted materials are not copyedited and are the sole responsibility of the authors, so questions or comments should be addressed to the corresponding author

Consisting of data provided by the authors to benefit the reader, the posted materials are not copyedited and are the sole responsibility of the authors, so questions or comments should be addressed to the corresponding author. Supplementary Material Supplementary Physique 1Click here for additional data file.(1.7M, png) Supplementary Physique 2Click here for additional data file.(537K, png) Supplementary Table 1Click here for additional data file.(16K, docx) Supplementary Physique LegendsClick here for additional data file.(13K, docx) Notes The authors gratefully acknowledge the contributions of the site investigators and site staff who conducted the P1072 study: Gaborone Prevention/Treatment Trials CRS: Charles Fane, RN/MW; Dudu Kooreng, RN; Tebogo J. and P1) and IFN (G1) in the HIV-1+ infants, whereas antirotavirus immunoglobulin A (IgA) levels were not. Heightened inflammation and immune activation in HIV-1+ infants did not alter IgA responses associated with protection from rotavirus disease. Clinical Trials Registration. 00880698 .001). HIV-1+ infants had significantly lower World Health Organization (WHO) weight-for-age scores compared with the HEU infants (median of ?1.5 vs ?0.7; = .001). Among the HIV-1+ infants, 63 of 68 (93%) had recently initiated combination antiretroviral treatment (ART) with a median (Q1, Q3) duration of 6 (0, 12) days prior to receiving vaccine. The 5 infants not on ART at study entry initiated ART within 28 days of the first vaccine dose. In the 65 AZD5582 HIV-1+ infants with plasma viral load (pVL) measured at study entry, the median pVL was 4.6 log10 copies/mL, and 61 (94%) had detectable HIV-1 RNA at 400 copies/mL. Following the third dose of RV5, 64 of the 68 HIV-1+ infants (median age, 179 days; median duration of ART, 105 days) had pVL measured; 32 of 64 (50%) had reached pVL of 400 RNA copies/mL. Table 1. Participant Characteristics valuescore, median (Q1, Q3)?1.5 (?2.4, ?0.2)?0.7 (?1.3, ?0.1).001bWHO height-for-age score, median (Q1, Q3)?1.1 (?2.1, ?0.2)?0.9 (?1.8, 0.0).23b Open in a separate window aChi-square test. bWilcoxon assessments. cAll human immunodeficiency virus type 1Cinfected infants started antiretroviral therapy within 28 days of entry. dOnly 65 of 68 human immunodeficiency virus type 1 (HIV-1)Cinfected infants had HIV-1 viral load results at Pdgfd entry. Abbreviations: ART, antiretroviral therapy; ARV, antiretroviral; cART, combination antiretroviral therapy; HIV-1, human immunodeficiency virus type 1; NA, not applicable; OPV, oral poliovirus vaccine; PMTCT, prevention of mother to child transmission; pVL, plasma viral load; WHO, World Health Organization. Inflammation and Immune Activation Profiles Before and After AZD5582 Pentavalent Rotavirus Vaccine HIV-1+ infants had significantly higher prevaccination concentrations of 7 (IFN, IL1-, IL-2, IL-6, IL-8, IL-10, and TNF) of the 10 cytokines measured compared with the HEU infants (Physique 1). In bivariate (adjusted for HIV-1 status) censored normal regression models, age at study entry (above or below the median age of 90 days) and ever having exposure to breastmilk were significantly associated with elevated concentrations of at least 1 inflammatory cytokine at study entry. In a multivariable model that included HIV-1 status and these 2 covariates, concentrations of IFN, IL1-, IL-2, IL-6, and IL-10 remained significantly higher in the HIV-1+ infants compared with the HEU infants (ranging from 1.65-fold for IL-1 to 2.20-fold for IL-6; Supplementary Table 1). In HIV-1+ infants, higher concentrations of IFN, IL-2, IL-10, and sCD14 were associated with higher pVL, with an 8%C23% increase for each log10 increase in pVL. Also in the HIV-1+ infants, lower WHO weight-for-age scores were associated with higher concentrations of IFN, IL-1, IL-2, IL-8, and IL-10 (Supplementary Physique 1). There were no significant increases relative to baseline in any of the cytokines 21 days after the first vaccine dose, in either AZD5582 AZD5582 the HIV-1+ or HEU infants, or in those receiving vaccine versus placebo (data not shown). Open in a separate window Physique 1. Baseline concentrations of plasma cytokines (interferon [IFN], interleukin 1 [IL-1], interleukin 2 [IL-2], interleukin 4 [IL-4], interleukin 6 [IL-6], interleukin 8 [IL-8], interleukin 10 [IL-10], interleukin 12p70 [IL-12p70], interleukin 13 [IL-13], and tumor necrosis factor [TNF]) and soluble CD 14 (sCD14) in human immunodeficiency virus type 1Cinfected (HIV-1+) and HIV uncovered but uninfected (HEU) African infants prior to receipt of pentavalent rotavirus vaccine (RV5) or placebo. Boxplots (showing individual data points, median [Q1, Q3], lower and upper fences [1.5 interquartile range]) of baseline concentrations of plasma cytokines. The median (minimum, maximum) limit of detection for each cytokine was as follows: IFN (0.45 [0.33, 1.16]), IL-1 (0.03 [0.03, 0.21]), IL-2 (0.10 [0.08, 0.23]), IL-4 (0.03 [0.02, 0.07]), IL-6 (0.09 [0.07, 0.14]), IL-8 (0.09 [0.05, 0.20]), IL-10 (0.10 [0.04, 0.13]), IL-12p70 (0.15 [0.09, 0.42]), IL-13 (0.47 [0.40, 0.98]), TNF (0.08 [0.05, 0.12]) pg/mL. The lower limit of detection of the assay for sCD14 was 125 pg/mL. Differences between HIV-1+ (n = 68) and HEU (n = 113) infants were assessed using Wilcoxon rank sum assessments. The percentage of measurements with values.