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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:BackgroundHIV infection and its management confer a substantial health burden to affected individuals and have been associated with increased risk of oral and dental diseases. In this study, we sought to quantify HIV-associated differences in the prevalence and severity of dental caries in the primary and permanent dentition of 4-11-year-old Nigerian Children.MethodsWe used clinical, laboratory, demographic, and behavioral data obtained from an ongoing cohort study of age-matched HIV-infected (HI, n = 181), HIV-exposed-but-uninfected (HEU, n = 177), and HIV-unexposed-and-uninfected (HUU, n = 186) children. Measures of dental caries experience (i.e., prevalence and severity) were based on dmft/DMFT indices recorded by trained and calibrated clinical examiners. Differences in primary and permanent dentition caries experience between HI, HEU, and HUU were estimated using multivariable logistic and negative binomial regression modeling.ResultsHI children had significantly higher caries experience (33%) compared to HEU (15%) and HUU (22%) children. This difference persisted in fully adjusted analyses [odds ratio (OR) = 1.6; 95% confidence interval (CI) = 1.0-2.6], was most pronounced in the permanent dentition (OR = 3.4; 95% CI = 1.2-9.5), and mirrored differences in caries severity. While molars were predominantly affected in both primary and permanent dentitions, caries lesion patterns differed between dentitions. Caries severity was significantly associated with hypoplastic primary teeth, gingival inflammation, and lower CD4 counts.ConclusionsWe found that the higher prevalence and severity of dental caries among HI children was driven by increased burden of permanent dentition caries compared to their uninfected counterparts. The dentition-specific associations identified in this study highlight the need to design and implement age-specific caries prevention strategies. These may include intensified oral hygiene regimens aimed at mitigating the cariogenic impact of hyposalivation among HI children. Similarly, the long-lasting impacts of developmental defects of the enamel in the primary and permanent dentitions must not be ignored.

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.).

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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