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Measles Immunity at 4.5 Years of Age Following Vaccination at 9 and 15-18 Months of Age Among Human Immunodeficiency Virus (HIV)-infected, HIV-exposed-uninfected, and HIV-unexposed Children.

ABSTRACT: BACKGROUND:Human immunodeficiency virus (HIV)-infected and HIV-exposed-uninfected (HEU) children may be at increased risk of measles infection due to waning of immunity following vaccination. We evaluated persistence of antibodies to measles vaccination at 4.5 years of age in HIV-unexposed, HEU, and HIV-infected children with CD4+ ?25% previously randomized to immediate antiretroviral therapy (ART) interrupted at 12 months (HIV/Immed-ART-12), 24 months (HIV/Immed-ART-24), or when clinically/immunologically indicated (HIV/Def-ART). The HIV/Def-ART group initiated ART by median 5.8 (interquartile range, 4.4-10.3) months of age. METHODS:In this study, HIV-unexposed (n = 95), HEU (n = 84), HIV/Immed-ART-12 (n = 70), HIV/Immed-ART-24 (n = 70), and HIV/Def-ART (n = 62) children were scheduled to receive measles vaccination at age 9 and 15-18 months. Antimeasles serum immunoglobulin G titers were quantified using enzyme-linked immunosorbent assay at 4.5 years. RESULTS:Compared with HIV-unexposed children (2860 mIU/mL), measles antibody geometric mean titers (GMTs) were significantly lower in both HIV/Immed-ART-12 (571; P < .001) and HIV/Immed-ART-24 (1136; P < .001) but similar in the HIV/Def-ART (2777) and HEU (3242) groups. Furthermore, compared with HIV-unexposed, antibody titers ?330 mIU/mL (ie, presumed serocorrelate for protection; 99%) were also significantly lower in HIV/Immed-ART-12 (70%; P < .001) and HIV/Immed-ART-24 (83%; P < .001) but similar in the HIV/Def-ART (90%) and HEU (98%) groups. CONCLUSIONS:HIV-infected children in whom ART was interrupted at either 12 or 24 months had lower GMTs and lower proportions with seroprotective titers than HIV-unexposed children, indicating a potential downside of ART treatment interruption. CLINICAL TRIALS REGISTRATION:NCT00099658 and NCT00102960.

SUBMITTER: Mutsaerts EAML

PROVIDER: S-EPMC6669279 | biostudies-literature | 2019 Aug

REPOSITORIES: biostudies-literature

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Measles Immunity at 4.5 Years of Age Following Vaccination at 9 and 15-18 Months of Age Among Human Immunodeficiency Virus (HIV)-infected, HIV-exposed-uninfected, and HIV-unexposed Children.

Mutsaerts Eleonora A M L EAML Nunes Marta C MC van Rijswijk Martijn N MN Klipstein-Grobusch Kerstin K Otwombe Kennedy K Cotton Mark F MF Violari Avy A Madhi Shabir A SA

Clinical infectious diseases : an official publication of the Infectious Diseases Society of America 20190801 4

<h4>Background</h4>Human immunodeficiency virus (HIV)-infected and HIV-exposed-uninfected (HEU) children may be at increased risk of measles infection due to waning of immunity following vaccination. We evaluated persistence of antibodies to measles vaccination at 4.5 years of age in HIV-unexposed, HEU, and HIV-infected children with CD4+ ≥25% previously randomized to immediate antiretroviral therapy (ART) interrupted at 12 months (HIV/Immed-ART-12), 24 months (HIV/Immed-ART-24), or when clinica ...[more]

PMID: 30418528

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Project description:Immunization and nutritional interventions are mainstays of child health programs in sub-Saharan Africa, yet few published data exist on their interactions. HIV-exposed (but uninfected) infants enrolled in a randomized placebo-controlled trial of multivitamin supplements (vitamins B complex, C, and E) conducted in Tanzania were sampled for an assessment of measles IgG quantity and avidity at 15 to 18 months. Infants were vaccinated between 8.5 and 12 months of age, and all mothers received high-dose multivitamins as the standard of care. Of 201 HIV-exposed infants who were enrolled, 138 (68.7%) were seropositive for measles. There were no effects of infant multivitamin supplementation on measles seroconversion proportions, IgG concentrations, or IgG avidity (P > 0.05). The measles seroconversion proportion was greater for HIV-exposed infants vaccinated at 10 to 11 months of age than for those vaccinated at 8.5 to 10 months (P = 0.032) and greater for infants whose mothers had a CD4 T-cell count of <200 cells/?l than for infants whose mothers had a CD4 T-cell count of >350 cells/?l (P = 0.039). Stunted infants had a significantly decreased IgG quantity compared to nonstunted infants (P = 0.012). As for measles avidity, HIV-exposed infants vaccinated at 10 to 11 months had increased antibody avidity compared to those vaccinated at 8.5 to 10 months (P = 0.031). Maternal CD4 T-cell counts of <200 cells/?l were associated with decreased avidity compared to counts of >350 cells/?l (P = 0.047), as were lower infant height-for-age z-scores (P = 0.016). Supplementation with multivitamins containing B complex, C, and E does not appear to improve measles vaccine responses for HIV-exposed infants. Studies are needed to better characterize the impact of maternal HIV disease severity on the immune system development of HIV-exposed infants and the effect of malnutrition interventions on vaccine responses. (This study has been registered at ClinicalTrials.gov under registration no. NCT00197730.).

Project description:HIV-exposed uninfected infants (HEU) have abnormal immunologic functions and increased infectious morbidity in the first 6 months of life, which gradually decreases thereafter. The mechanisms underlying HEU immune dysfunctions are unknown. We hypothesized that unique characteristics of the HEU gut microbiota associated with maternal HIV status may underlie the HEU immunologic dysfunctions. We characterized the infant gut, maternal gut, and breast milk microbiomes of mother-infant pairs, including 123 with HEU and 117 with HIV-uninfected infants (HUU), from South Africa. Pan-bacterial 16S rRNA gene sequencing was performed on (i) infant stool at 6, 28, and 62 weeks; (ii) maternal stool at delivery and 62 weeks; and (iii) breast milk at 6 weeks. Infant gut alpha and beta diversities were similar between groups. Microbial composition significantly differed, including 12 genera, 5 families and 1 phylum at 6 weeks; 12 genera and 2 families at 28 weeks; and 2 genera and 2 families at 62 weeks of life. Maternal gut microbiomes significantly differed in beta diversity and microbial composition, and breast milk microbiomes differed in microbial composition only. Infant gut microbiotas extensively overlapped with maternal gut and minimally with breast milk microbiotas. Nevertheless, exclusively breastfed HEU and HUU had less divergent microbiomes than nonexclusively breastfed infants. Feeding pattern and maternal gut microbiome imprint the HEU gut microbiome. Compared to HUU, the HEU gut microbiome prominently differs in early infancy, including increased abundance of taxa previously observed to be present in excess in adults with HIV. The HEU and HUU gut microbiome compositions converge over time, mirroring the kinetics of HEU infectious morbidity risk. IMPORTANCE HIV-exposed uninfected infants (HEU) are highly vulnerable to infections in the first 6 months of life, and this vulnerability decreases to the age of 24 months. Because the microbiome plays a critical role in the education of the infant immune system, which protects them against infections, we characterized the gut microbiomes of HEU and HIV-unexposed infants (HUU) in the first year of life. The HEU and HUU gut microbiomes showed prominent differences at 6 and 28 weeks of life but converged at 62 weeks of life, mirroring the time course of the HEU excess infectious morbidity and suggesting a potential association between the infant gut microbiome structure and susceptibility to infections. Infant gut microbiotas extensively overlapped with maternal gut and minimally with breast milk microbiotas. Moreover, exclusively breastfed HEU and HUU had less divergent microbiomes at 6 and 28 weeks than nonexclusively breastfed HEU and HUU. The factors that affect the HEU gut microbiome, maternal gut microbiome and exclusive breastfeeding, may be targeted by interventions.

Dataset Information

Measles Immunity at 4.5 Years of Age Following Vaccination at 9 and 15-18 Months of Age Among Human Immunodeficiency Virus (HIV)-infected, HIV-exposed-uninfected, and HIV-unexposed Children.

Publications

Measles Immunity at 4.5 Years of Age Following Vaccination at 9 and 15-18 Months of Age Among Human Immunodeficiency Virus (HIV)-infected, HIV-exposed-uninfected, and HIV-unexposed Children.

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