Early ART results in greater immune reconstitution benefits in HIV-infected infants : working with data missingness in a longitudinal dataset

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dc.contributor.authorAzzoni, Livioen_ZA
dc.contributor.authorBarbour, Russellen_ZA
dc.contributor.authorPapasavvas, Emmanouilen_ZA
dc.contributor.authorGlencross, Deborah K.en_ZA
dc.contributor.authorStevens, Wendy S.en_ZA
dc.contributor.authorCotton, Mark F.en_ZA
dc.contributor.authorViolari, Avyen_ZA
dc.contributor.authorMontaner, Luis J.en_ZA
dc.date.accessioned2016-08-23T11:55:47Z
dc.date.available2016-08-23T11:55:47Z
dc.date.issued2015
dc.descriptionCITATION: Azzoni, L.,et al. 2015. Early ART results in greater immune reconstitution benefits in HIV-infected infants : working with data missingness in a longitudinal dataset. PLoS ONE, 10(12):1-20, doi:10.1371/journal.pone.0145320.
dc.descriptionThe original publication is available at http://journals.plos.org/plosone
dc.description.abstractBackground: Early initiation of anti-retroviral treatment (ART) decreases mortality as compared to deferred treatment, but whether it preserves immune cells from early loss or promotes their recovery remains undefined. Determination of complex immunological endpoints in infants is often marred by missing data due to missed visits and/or inadequate sampling. Specialized methods are required to address missingness and facilitate data analysis. Methods: We characterized the changes in cellular and humoral immune parameters over the first year of life in 66 HIV-infected infants (0–1 year of age) enrolled in the CHER study starting therapy within 12 weeks of birth (n = 42) or upon disease progression (n = 24). A convenience cohort of 23 uninfected infants aged 0–6 months born to mothers with HIV-1 infection was used as controls. Flow cytometry and ELISA were used to evaluate changes in natural killer (NK) cells, plasmacytoid dendritic cells (pDC), and CD4+ or CD8+ T-cell frequencies. Data missingness was assessed using Little's test. Complete datasets for analysis were created using Multiple Imputation (MI) or Bayesian modeling and multivariate analysis was conducted on the imputed datasets. Results: HIV-1-infected infants had greater frequency of CD4+ T cells with naïve phenotype, as well as higher serum IL-7 levels than HIV exposed/uninfected infants. The elevated data missingness was completely at random, allowing the use of both MI and Bayesian modeling. Both methods indicate that early ART initiation results in higher CD4+ T cell frequency, lower expression of CD95 in CD8+ T cell, and preservation of naïve T cell subsets. In contrast, innate immune effectors appeared to be similar independently of the timing of ART initiation. Conclusions: Early ART initiation in infants with perinatal HIV infection reduces immune activation and preserves an early expansion of naïve T-cells with undiminished innate cell numbers, giving greater immune reconstitution than achieved with deferred ART. Both statistical approaches concurred in this finding.en_ZA
dc.description.urihttp://journals.plos.org/plosone/article?id=10.1371/journal.pone.0145320
dc.description.versionPublisher's version
dc.format.extent20 pages
dc.identifier.citationAzzoni, L.,et al. 2015. Early ART results in greater immune reconstitution benefits in HIV-infected infants : working with data missingness in a longitudinal dataset. PLoS ONE, 10(12):1-20, doi:10.1371/journal.pone.0145320
dc.identifier.issn1932-6203 (online)
dc.identifier.otherdoi:10.1371/journal.pone.0145320
dc.identifier.urihttp://hdl.handle.net/10019.1/99444
dc.language.isoen_ZAen_ZA
dc.publisherPublic Library of Science
dc.rights.holderAuthors retain copyright
dc.subjectAnti-retroviral treatmenten_ZA
dc.subjectHIV-infected infants -- Mortalityen_ZA
dc.subjectImmune system -- Testingen_ZA
dc.subjectAnti-retroviral agentsen_ZA
dc.subjectHIV-positive children -- Early treatment -- Testingen_ZA
dc.titleEarly ART results in greater immune reconstitution benefits in HIV-infected infants : working with data missingness in a longitudinal dataseten_ZA
dc.typeArticleen_ZA
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