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Impact of highly active antiretroviral therapy initiation on CD4(+) T-cell repopulation in duodenal and rectal mucosa.

ABSTRACT: OBJECTIVE:The objective of this study was to assess the effects of HAART initiation on CD4(+) T-cell repopulation and T-cell immune activation in rectal and duodenal mucosa. DESIGN:The effects of HAART on the gastrointestinal tract remain controversial, and studies have reached different conclusions regarding its effectiveness at restoring mucosal CD4(+) T cells depending upon time of initiation, duration of treatment and gastrointestinal tract region studied. METHODS:We obtained blood, rectal biopsies and duodenal biopsies from 14 chronically infected individuals at baseline and at 4-9 months post-HAART initiation. We examined CD4(+) T-cell frequencies in blood, rectum and duodenum at both time points, and performed a detailed assessment of CD4(+) T-cell phenotype, immune activation marker expression and HIV-specific CD8(+) T-cell responses in blood and rectal mucosa. RESULTS:CD4(+) T-cell percentages increased significantly in blood, rectal and duodenal mucosa after 4-9 months of HAART (P?=?0.02, 0.0005, 0.0002), but remained lower than in uninfected controls. HIV-specific CD8(+) T-cell responses in blood and rectal mucosa declined following HAART initiation (P?=?0.0015, 0.021). CD8(+) T-cell coexpression of CD38 and HLA-DR in blood and mucosa, as well as plasma sCD14, declined significantly. CD28 expression on blood and mucosal CD8(+) T cells increased, whereas programmed death receptor-1 expression on blood HIV-specific CD4(+) and CD8(+) T cells decreased. CONCLUSION:Within the first months of HAART, limited CD4(+) T-cell reconstitution occurs in small and large intestinal mucosa. Nevertheless, decreased immune activation and increased CD28 expression suggest rapid immunological benefits of HAART despite incomplete CD4(+) T-cell reconstitution.

SUBMITTER: Hayes TL

PROVIDER: S-EPMC4026034 | biostudies-literature | 2013 Mar

REPOSITORIES: biostudies-literature

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Impact of highly active antiretroviral therapy initiation on CD4(+) T-cell repopulation in duodenal and rectal mucosa.

Hayes Timothy L TL Asmuth David M DM Critchfield J William JW Knight Thomas H TH McLaughlin Bridget E BE Yotter Tammy T McConnell Delandy H DH Garcia Juan Carlos JC Pollard Richard B RB Shacklett Barbara L BL

AIDS (London, England) 20130301 6

<h4>Objective</h4>The objective of this study was to assess the effects of HAART initiation on CD4(+) T-cell repopulation and T-cell immune activation in rectal and duodenal mucosa.<h4>Design</h4>The effects of HAART on the gastrointestinal tract remain controversial, and studies have reached different conclusions regarding its effectiveness at restoring mucosal CD4(+) T cells depending upon time of initiation, duration of treatment and gastrointestinal tract region studied.<h4>Methods</h4>We ob ...[more]

PMID: 23262500

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Project description:Introduction:Human immunodeficiency virus (HIV) infection results in a gradual depletion of immune function, particularly CD4 cells. The CD4 assessment plays a significant role in assessing treatment responses and clinical decision-making for patients on combination antiretroviral therapy (ART) in resource-limited settings. However, new data on CD4 count changes are scarce; the volatility of CD4 counts after initiation of ART over time remains largely uncharacterized. This study aimed to identify the predictors of CD4 changes over time among HIV-infected children who began ART in Amhara, Ethiopia. Methods:A retrospective follow-up study was performed. A total of 983 HIV-infected children who initiated ART in government hospitals in the Amhara region between 2010 and 2016 were included using a simple random sampling technique. Data were extracted using a structured checklist. An exploratory data analysis was carried out to explain individual and average profile plots. The linear mixed model was used to identify the CD4 change count predictors over time. Variables with p value < 0.05 were considered statistically significant in a multivariable linear mixed regression analysis. Results:The mean CD4 count of the participants was 465.1 cells/mm3 with an average CD4 count increase of 30.06 cells/mm3 over 6 months from baseline CD4 count and ART initiation. Childhood age (? = - 0.015; 95% Cl - 0.021, - 0.009), opportunistic infection at ART initiation (? = - 0.044, 95% CI - 0.085, - 0.004), hemoglobin level (? = 0.013; 95% CI 0.004, 0.022), and baseline WHO clinical stage II (? = - 0.046, 95% CI - 0.091, - 0.0003) were significant predictors of CD4 changes over time. Conclusions:The average CD4 count increase was sufficient in HIV patients who began combined antiretroviral therapy over time. The younger age of the infant, the higher baseline level of hemoglobin, the baseline WHO clinical stage II, and opportunistic infections led to changes in CD4 counts. As a result, timely diagnosis and treatment of opportunistic infections will reduce the risk of opportunistic infections.

Dataset Information

Impact of highly active antiretroviral therapy initiation on CD4(+) T-cell repopulation in duodenal and rectal mucosa.

Publications

Impact of highly active antiretroviral therapy initiation on CD4(+) T-cell repopulation in duodenal and rectal mucosa.

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