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T-Cell Subsets Predict Mortality in Malnourished Zambian Adults Initiating Antiretroviral Therapy.

Chisenga CC, Filteau S, Siame J, Chisenga M, Prendergast AJ, Kelly P - PLoS ONE (2015)

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Tropical Gastroenterology and Nutrition group, University of Zambia School of Medicine, Lusaka, Zambia; NUSTART project, University Teaching Hospital, Lusaka, Zambia.

ABSTRACT

Objective: To 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.

Methods: This 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.

Results: Among 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.

Conclusions: 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.

No MeSH data available.


Related in: MedlinePlus

Flow of participants through the study.
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pone.0129928.g001: Flow of participants through the study.

Mentions: A total of 189 HIV-infected adult men and women were enrolled in this sub-study and randomised to either LNS or LNS-VM. Participants were excluded from analysis if some baseline CD4+ and CD8+ T-cell panel data were missing (n = 3 LNS and n = 5 LNS-VM). Of the remaining 181 participants, 90 were in the LNS and 91 in the LNS-VM group (Fig 1). Groups randomised to LNS and LNS-VM were very similar (Table 1). Those who died had lower total CD4+ cell count, lower grip strength and a small difference in BMI than survivors (Table 1). Among all participants in this sub study, the median CD4 count at week 0 (enrolment) was 98 (IQR 64, 211) and at week 12 (primary endpoint) was 259 (IQR 166, 389) (p<0.0001).


T-Cell Subsets Predict Mortality in Malnourished Zambian Adults Initiating Antiretroviral Therapy.

Chisenga CC, Filteau S, Siame J, Chisenga M, Prendergast AJ, Kelly P - PLoS ONE (2015)

Flow of participants through the study.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4470912&req=5

pone.0129928.g001: Flow of participants through the study.
Mentions: A total of 189 HIV-infected adult men and women were enrolled in this sub-study and randomised to either LNS or LNS-VM. Participants were excluded from analysis if some baseline CD4+ and CD8+ T-cell panel data were missing (n = 3 LNS and n = 5 LNS-VM). Of the remaining 181 participants, 90 were in the LNS and 91 in the LNS-VM group (Fig 1). Groups randomised to LNS and LNS-VM were very similar (Table 1). Those who died had lower total CD4+ cell count, lower grip strength and a small difference in BMI than survivors (Table 1). Among all participants in this sub study, the median CD4 count at week 0 (enrolment) was 98 (IQR 64, 211) and at week 12 (primary endpoint) was 259 (IQR 166, 389) (p<0.0001).

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Tropical Gastroenterology and Nutrition group, University of Zambia School of Medicine, Lusaka, Zambia; NUSTART project, University Teaching Hospital, Lusaka, Zambia.

ABSTRACT

Objective: To 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.

Methods: This 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.

Results: Among 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.

Conclusions: 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.

No MeSH data available.


Related in: MedlinePlus