Dataset Information

Naive CD4⁺ cell counts significantly decay and high HIV RNA levels contribute to immunological progression in long-term non-progressors infected with HIV by blood products: a cohort study.

ABSTRACT:

Background

Some long-term non-progressors (LTNPs) have decreasing CD4⁺ T cell counts and progress to AIDS. Exploring which subsets of CD4⁺ T cell decreasing and the determinants associated with the decay in these patients will improve disease progression surveillance and provide further understanding of HIV pathogenesis.

Methods

Twenty-five LTNPs infected with HIV by blood products were classified as decreased (DG) if their CD4⁺ cell count dropped to < 400 cells/μL during follow-up or as non-decreased (non-DG) if their CD4⁺ cell count was ≥400 cells/μL. Laboratory and clinical assessments were conducted at 6 consecutive visits to identify DG characteristics.

Results

The LTNPs were infected with HIV for 12 (IQR: 11.5-14) years, and 23 were classified as the B' subtype. Six individuals lost LTNP status 14.5 (IQR: 12.5-17.5) years after infection (DG), and the CD4⁺ T cell count decreased to 237 (IQR: 213-320) cells/μL at the latest visit. The naïve CD4⁺ T cell count decrease was greater than that of memory CD4⁺ T cells [- 128 (IQR: - 196, - 107) vs - 64 (IQR: - 182, - 25) cells/μL)]. Nineteen individuals retained LTNP status (non-DG). At enrolment, the viral load (VL) level (p = 0.03) and CD8⁺CD38⁺ percentage (p = 0.03) were higher in DG than non-DG individuals. During follow-up, viral load and CD8⁺CD38⁺ percentage were significantly increased and negatively associated with CD4⁺ cell count [(r = - 0.529, p = 0.008), (r = - 0.476, p = 0.019), respectively]. However, the CD8⁺CD28⁺ percentage and B cell count dropped in DG and were positively correlated with CD4⁺ T cell count [(r = 0.448, p = 0.028), (r = 0.785, p < 0.001)].

Conclusion

Immunological progression was mainly characterized by the decrease of naïve CD4⁺ T cell in LTNPs infected with HIV by blood products and it may be associated with high HIV RNA levels.

SUBMITTER: Xu L

PROVIDER: S-EPMC8173962 | biostudies-literature | 2021 Jun

REPOSITORIES: biostudies-literature

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Publications

Naïve CD4<sup>+</sup> cell counts significantly decay and high HIV RNA levels contribute to immunological progression in long-term non-progressors infected with HIV by blood products: a cohort study.

Xu Ling L Liu Yubin Y Song Xiaojing X Li Yanling Y Han Yang Y Zhu Ting T Cao Wei W Li Taisheng T

BMC immunology 20210603 1

<h4>Background</h4>Some long-term non-progressors (LTNPs) have decreasing CD4<sup>+</sup> T cell counts and progress to AIDS. Exploring which subsets of CD4<sup>+</sup> T cell decreasing and the determinants associated with the decay in these patients will improve disease progression surveillance and provide further understanding of HIV pathogenesis.<h4>Methods</h4>Twenty-five LTNPs infected with HIV by blood products were classified as decreased (DG) if their CD4<sup>+</sup> cell count dropped ...[more]

PMID: 34082709

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Project description:BackgroundCD4+ T cell counts in certain human immunodeficiency virus (HIV)-infected patients called immunological non-responders (INRs) could not return to a normal level even with sustained antiretroviral therapy (ART) because of persistent immune activation, which is associated with pro-inflammatory cytokines production and an altered intestinal microbiome profile. Changes in gut bacterial composition have been linked to low CD4+ T cell counts in HIV-infected individuals. However, the association between CD4+ T cell counts and gut microbiota community composition and cytokines levels in INRs (CD4+ T cell counts < 500 cells/μL) from Yunnan Province, China, has not been previously investigated.MethodsTo address this issue, we carried out a cross-sectional study of 34 HIV-infected INRs. The patients were divided into CD4 count > 200 cells/μL group and CD4 count < 200 cells/μL group. The gut microbiota composition of each subject was analyzed by 16S rRNA gene sequencing. We also compared CD8+ T cell counts, pro-inflammatory cytokines levels, and nutritional status between the two groups.ResultsCompared to INRs with CD4 count > 200 cells/μL, those with CD4 count < 200 cells/μL had a lower CD4/CD8 ratio, lower nutritional status and higher serum levels of tumor necrosis factor (TNF)-α, interferon-γ-inducible protein (IP)-10 and interleukin (IL)-1α. Ruminococcaceae was less abundant in the CD4 count < 200 cells/μL group than in the CD4 count > 200 cells/μL group, and difference in alpha diversity was observed between the two groups. Moreover, CD4+ T cell counts were negatively associated with TNF-α and IL-1α levels and positively associated with the relative abundance of Ruminococcaceae.ConclusionsOur study demonstrated that lower CD4+ T cell counts in INRs are associated with a reduced abundance of Ruminococcaceae in the gut and elevated serum pro-inflammatory cytokines levels. Thus, interventions targeting gut microbiota to increase CD4+ T cell counts are a potential strategy for promoting immune reconstitution in HIV-infected INRs.

Project description:Immunological non-responders (InRs) are HIV-infected individuals in whom the administration of combination antiretroviral therapy (cART), although successful in suppressing viral replication, cannot properly reconstitute patient circulating CD4+ T-cell number to immunocompetent levels. The causes for this immunological failure remain elusive, and no therapeutic strategy is available to restore a proper CD4+ T-cell immune response in these individuals. We have recently demonstrated that platelets harboring infectious HIV are a hallmark of InR, and we now report on a causal connection between HIV-containing platelets and T-cell dysfunctions. We show here that in vivo, platelet-T-cell conjugates are more frequent among CD4+ T cells in InRs displaying HIV-containing platelets (<350 CD4+ T cells/μl blood for >1 year) as compared with healthy donors or immunological responders (IRs; >350 CD4+ T cells/μl). This contact between platelet containing HIV and T cell in the conjugates is not infectious for CD4+ T cells, as coculture of platelets from InRs containing HIV with healthy donor CD4+ T cells fails to propagate infection to CD4+ T cells. In contrast, when macrophages are the target of platelets containing HIV from InRs, macrophages become infected. Differential transcriptomic analyses comparing InR and IR CD4+ T cells reveal an upregulation of genes involved in both aerobic and anaerobic glycolysis in CD4+ T cells from InR vs. IR individuals. Accordingly, InR platelets containing HIV induce a dysfunctional increase in glycolysis-mediated energy production in CD4+ T cells as compared with T cells cocultured with IR platelets devoid of virus. In contrast, macrophage metabolism is not affected by platelet contact. Altogether, this brief report demonstrates a direct causal link between presence of HIV in platelets and T-cell dysfunctions typical of InR, contributing to devise a platelet-targeted therapy for improving immune reconstitution in these individuals.

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Dataset Information

Naive CD4⁺ cell counts significantly decay and high HIV RNA levels contribute to immunological progression in long-term non-progressors infected with HIV by blood products: a cohort study.

Background

Methods

Results

Conclusion

Publications

Naïve CD4<sup>+</sup> cell counts significantly decay and high HIV RNA levels contribute to immunological progression in long-term non-progressors infected with HIV by blood products: a cohort study.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Dataset Information

Naive CD4+ cell counts significantly decay and high HIV RNA levels contribute to immunological progression in long-term non-progressors infected with HIV by blood products: a cohort study.

Background

Methods

Results

Conclusion

Publications

Naïve CD4<sup>+</sup> cell counts significantly decay and high HIV RNA levels contribute to immunological progression in long-term non-progressors infected with HIV by blood products: a cohort study.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Naive CD4⁺ cell counts significantly decay and high HIV RNA levels contribute to immunological progression in long-term non-progressors infected with HIV by blood products: a cohort study.