Immunologic Basis for Revaccination of HIV-Infected Children Receiving HAART

Rainwater-Lovett, Kaitlin; Moss, William J.

doi:10.2217/fvl.10.75

Cited by 16 publications

(19 citation statements)

References 101 publications

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“…In the present study, depletion of SM B cells was observed in contrast to study by Jacobsen et al; this could be due to the younger age of children in the present cohort as SM cells generally accumulate with age. This preferential depletion of SM B cell pool emphasize the need to revaccinate HIV infected children receiving HAART as reported in previous studies …”

Section: Discussionsupporting

confidence: 76%

Impact of HIV infection and highly active antiretroviral therapy (HAART) on B cell subpopulations in children

Singh

Mukherjee

Singla

et al. 2018

Journal of Medical Virology

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B-cells play an important role in defending children against various infections. In view of scare data, we undertook this prospective cohort study to describe B cell compartment in HIV infected children (<5 years of age) and the effect of HAART on B cell subpopulations. HIV infected children (<5 years) from Pediatric HIV services of the Department of Pediatrics, All India Institute of Medical Sciences, New Delhi, were recruited (April 2012-December 2015). The enrolled HIV-1 infected children (n = 59) were followed up regularly for 12 months; healthy controls (n = 51) included HIV uninfected children with no major illness. Flow cytometry was performed on fresh EDTA-treated blood samples to characterize B cell subpopulations. In HIV-infected children, marked depletion of naive (P = 0.003), non-switched memory (P = 0.02), mature (P = 0.0005), resting memory (P < 0.0001) B cells, and expansion of double negative memory (P < 0.0001), activated memory (P < 0.0001) and tissue like memory (P < 0.0001) B cells were observed as compared to healthy controls. In children started on HAART, at the end of 12 months of therapy, frequencies of non-switched memory (P = 0.04), switched memory (P = 0.01), and resting memory (P = 0.003) B cells were lower; activated memory (P = 0.04), and tissue-like memory (P = 0.0001) B cells were still higher than healthy controls. HIV infection resulted in reduced memory B cells in HIV infected children. Following HAART, there was normalization of some B cell subpopulations. The study emphasizes the need of re-vaccination in HIV infected children to maintain the memory B cell pool and adequate humoral immune response against infections.

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Section: Discussionsupporting

confidence: 76%

Impact of HIV infection and highly active antiretroviral therapy (HAART) on B cell subpopulations in children

Singh

Mukherjee

Singla

et al. 2018

Journal of Medical Virology

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“…As in our study, other studies of measles revaccination in HIV-infected children on ART found that the response was related more to suppressed HIV replication than to CD4% 24,31 . This suggests that the ability to sustain an immune response to measles vaccination may be hindered by high levels of HIV replication, which is associated with turnover and depletion of B and T cells needed for memory 23 .…”

Section: Discussionmentioning

confidence: 99%

“…Maintenance of measles seropositivity after revaccination may involve a different immunological mechanism than measles seroconversion 23 , thus a separate analysis was performed to explore factors associated with seroconversion. We assessed the risk of measles seroconversion at 24 months post revaccination by log-binomial regression with robust error variance.…”

Section: Methodsmentioning

confidence: 99%

Sustained Responses to Measles Revaccination at 24 Months in HIV-infected Children on Antiretroviral Therapy in Kenya

Newman

Njoroge

Magaret³

et al. 2017

Pediatric Infectious Disease Journal

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Background There are limited data on whether HIV-infected children in resource-limited countries who are receiving antiretroviral therapy (ART) are able to produce sustained, protective levels of measles antibody after multiple measles vaccinations. Methods We administered an additional measles vaccine to HIV-infected children 15 months to 12 years of age receiving ART in Nairobi, Kenya. Measles antibody concentrations were determined by enzyme-linked immunosorbent assay (ELISA) at enrollment, one month, 12 months, and 24 months post revaccination. Results At enrollment, 125 (54%) of 232 study participants had protective concentrations of measles antibody. Measles seropositivity increased to 98% of all children at one month post revaccination, but decreased to 71% at 12 months, and 60% at 24 months post revaccination. Measles seroconversion and sustained measles seropositivity among those who were measles seronegative at enrollment was 25% at 24 months post revaccination. In this group, 39% of children with <50 copies/mL plasma HIV RNA measles seroconverted compared with 4% of children with plasma HIV RNA ≥1,000 copies/mL (p=0.018). Conclusions Measles revaccination can result in a sustained antibody response in a subset of HIV-infected children receiving ART, especially among those with HIV suppression.

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“…In healthy children younger than 10 years of age, the proportions of naïve T cells decrease as the immune system matures and encounters antigens, while memory T cell proportions increase. 5 Since control children were enrolled for only a single visit, our ability to differentiate between phenomena associated with aging, such as antigen exposure, and HAART duration was limited when comparing cellular subsets among HIV-infected children. We attempted to control for this by adjusting for age in statistical models and believe a large part of the considerable changes in T cell subsets can be attributed to HAART, as observed upon stratification of cell subset trajectories by age and sex.…”

Section: Discussionmentioning

confidence: 99%

Changes in Cellular Immune Activation and Memory T-Cell Subsets in HIV-Infected Zambian Children Receiving HAART

Rainwater-Lovett

Nkamba

Mubiana‐Mbewe

et al. 2014

JAIDS Journal of Acquired Immune Deficiency Syndromes

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Background Increased exposure to a broad array of pathogens in children residing in sub-Saharan Africa may lead to heightened immune activation and increased proportions of memory T cells. Changes in the size of these cellular subsets have implications for restoration of normal immune function after treatment with HAART and are not well-characterized in young sub-Saharan African children. Methods CD4+ and CD8+ T cell subsets were measured by flow cytometry in 157 HIV-infected Zambian children before and at 3-month intervals during HAART for up to 30 months and in 34 control children at a single study visit. Results Prior to HAART, HIV-infected children had higher levels of activated and effector memory (EM) CD4+ and CD8+ T cells, and lower levels of naïve T cells and CD8+ T cells expressing IL-7Rα, compared to control children. The median duration of follow-up was 14.9 months (IQR: 6.4, 23.2) among 120 HIV-infected children with at least one study follow-up visit. Levels of immune activation and EM CD4+ T cells declined within six months of HAART but the percentages of EM CD4+ T cells and effector CD8+ T cells remained elevated through 30 months of HAART. IL-7Rα-expressing CD8+ T cells increased with HAART, suggesting expansion of memory capacity. Conclusions HAART significantly reduced levels of immune activation and EM CD4+ T cells, and promoted reconstitution of naïve T cells and IL-7Rα-expressing CD8+ T cells. However, persistently high levels of EM CD4+ T cells in HIV-infected children may reflect chronic perturbations in T cell subset composition.

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Immunologic Basis for Revaccination of HIV-Infected Children Receiving HAART

Cited by 16 publications

References 101 publications

Impact of HIV infection and highly active antiretroviral therapy (HAART) on B cell subpopulations in children

Impact of HIV infection and highly active antiretroviral therapy (HAART) on B cell subpopulations in children

Sustained Responses to Measles Revaccination at 24 Months in HIV-infected Children on Antiretroviral Therapy in Kenya

Changes in Cellular Immune Activation and Memory T-Cell Subsets in HIV-Infected Zambian Children Receiving HAART

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