Abstract
ObjectiveTo estimate the prognostic value of T-cell subsets in Zambian patients initiating antiretroviral therapy (ART), and to assess the impact of a nutritional intervention on T-cell subsets.MethodsThis was a sub-study of a randomised clinical trial of a nutritional intervention for malnourished adults initiating ART. Participants in a randomised controlled trial (NUSTART trial) were enrolled between April and December 2012. Participants received lipid-based nutritional supplement either with or without additional vitamins and minerals. Immunophenotyping was undertaken at baseline and, in survivors, after 12 weeks of ART to characterize T-cell subsets using the markers CD3, CD4, CD8, CD45RA, CCR7, CD28, CD57, CD31, α4β7, Ki67, CD25 and HLA-DR. Univariate and multivariate survival analysis was performed, and responses to treatment were analysed using the Wicoxon rank-sum test.ResultsAmong 181 adults, 36 (20%) died by 12 weeks after starting ART. In univariate analysis, patients who died had fewer proliferating, more naïve and fewer gut homing CD4+ T-cells compared to survivors; and more senescent and fewer proliferating CD8+ T-cells. In a multivariate Cox regression model high naïve CD4+, low proliferating CD4+, high senescent CD8+ and low proliferating CD8+ subsets were independently associated with increased risk of death. Recent CD4+ thymic emigrants increased less between recruitment and 12 weeks of ART in the intervention group compared to the control group.ConclusionsSpecific CD4+ T-cell subsets are of considerable prognostic significance for patients initiating ART in Zambia, but only thymic output responded to this nutritional intervention.
Highlights
The annual number of AIDS-related deaths has declined from 2.3 (2.1–2.6) million in 2005, to 1.6 (1.4–1.9) million in 2012 [1] with the expansion of antiretroviral therapy (ART) provision in sub-Saharan Africa, studies consistently report high mortality during the first 6 months following ART initiation [2,3]
Recent CD4+ thymic emigrants increased less between recruitment and 12 weeks of ART in the intervention group compared to the control group
Specific CD4+ T-cell subsets are of considerable prognostic significance for patients initiating ART in Zambia, but only thymic output responded to this nutritional intervention
Summary
The annual number of AIDS-related deaths has declined from 2.3 (2.1–2.6) million in 2005, to 1.6 (1.4–1.9) million in 2012 [1] with the expansion of antiretroviral therapy (ART) provision in sub-Saharan Africa, studies consistently report high mortality during the first 6 months following ART initiation [2,3]. There is very little evidence regarding the prognostic value of specific T-cell subsets on early mortality [6,7]. Studies that have evaluated baseline T-cell subsets have reported that, in HIV-infected untreated adults, more activated CD8+ T-cells [7], and fewer CD28+ CD4+ T-cells [8] or naïve CD4+ T-cells independently predicted mortality [9]. In recently HIV-infected and untreated adults, low proportions of senescent (CD57+) CD4+ T-cells were associated with 5-fold higher odds of mortality [8]. In Zambian children, more CD8+ effector T-cells with fewer CD4+ central memory T-cells was associated with increased risk of mortality [6]
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