T-cell homeostasis alteration in HIV-1 infected subjects with low CD4 T-cell count despite undetectable virus load during HAART

Marziali, Marco; Santis, Wladimiro De; Carello, Rossella; Leti, Wilma; Esposito, Antonella; Isgrò, Antonella; Fimiani, Caterina; Sirianni, Maria Caterina; Mezzaroma, Ivano; Aiuti, F

doi:10.1097/01.aids.0000247588.69438.fd

Cited by 98 publications

(78 citation statements)

References 48 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…However, the link between persistent activation of CD8 + T cells and immune response to HAART is unclear. Here, in agreement with other studies [10,14,15], we found that the CD8 +…”

Section: Discussionsupporting

confidence: 94%

“…Immune activation has also been implicated in the occurrence of iIR [10,27]. Interestingly, in the current study, CD8…”

Section: Discussionsupporting

confidence: 45%

“…+ T cells) in iIR compared with HIV-infected patients with a better immunological recovery [10]. There are some explanations for such discrepancies.…”

Section: Cd38mentioning

confidence: 94%

“…+ T cells) in iIR patients compared with patients with an appropriate immune recovery [10][11][12][13]. However, these results have been challenged recently [10,14,15].…”

Section: Cd38mentioning

confidence: 99%

See 3 more Smart Citations

Association between discordant immunological response to highly active anti-retroviral therapy, regulatory T cell percentage, immune cell activation and very low-level viraemia in HIV-infected patients

Saison

Ferry

Demaret

et al. 2014

Clinical and Experimental Immunology

View full text Add to dashboard Cite

SummaryThe mechanisms sustaining the absence of complete immune recovery in HIV-infected patients upon long-term effective highly active anti-retroviral therapy (HAART) remain elusive. Immune activation, regulatory T cells (Tregs) or very low-level viraemia (VLLV) have been alternatively suspected, but rarely investigated simultaneously. We performed a cross-sectional study in HIV-infected aviraemic subjects (mean duration of HAART: 12 years) to concomitantly assess parameters associated independently with inadequate immunological response. Patients were classified as complete immunological responders (cIR, n = 48) and inadequate immunological responders (iIR, n = 39), depending on the CD4 + T cell count (> or < 500/mm 3 ). Clinical and virological data (including very low-level viraemia) were collected. In parallel, immunophenotyping of CD4 + lymphocytes, including Treg subsets, and CD8 + T cells was performed. Percentages of activated CD4 + T cells, Tregs, effector Tregs and terminal effector Tregs were found to be significantly elevated in iIR. Neither the percentage of activated CD8+ T cells nor VLLV were found to be associated with iIR. In the multivariate analysis, nadir of CD4 + T cell count and percentage of Tregs were the only two parameters associated independently with iIR [odds ratio (OR) = 2·339, P = 0·001, and OR = 0·803, P = 0·041]. We present here the largest study investigating simultaneously the immune response to long-term HAART, activation of CD4 + and CD8+ T cells, Treg percentages and very low-level viraemia. Causative interactions between Tregs and CD4 + T cells should now be explored prospectively in a large patients cohort.

show abstract

“…However, the link between persistent activation of CD8 + T cells and immune response to HAART is unclear. Here, in agreement with other studies [10,14,15], we found that the CD8 +…”

Section: Discussionsupporting

confidence: 94%

“…Immune activation has also been implicated in the occurrence of iIR [10,27]. Interestingly, in the current study, CD8…”

Section: Discussionsupporting

confidence: 45%

“…+ T cells) in iIR compared with HIV-infected patients with a better immunological recovery [10]. There are some explanations for such discrepancies.…”

Section: Cd38mentioning

confidence: 94%

“…+ T cells) in iIR patients compared with patients with an appropriate immune recovery [10][11][12][13]. However, these results have been challenged recently [10,14,15].…”

Section: Cd38mentioning

confidence: 99%

See 2 more Smart Citations

Association between discordant immunological response to highly active anti-retroviral therapy, regulatory T cell percentage, immune cell activation and very low-level viraemia in HIV-infected patients

Saison

Ferry

Demaret

et al. 2014

Clinical and Experimental Immunology

View full text Add to dashboard Cite

show abstract

“…T reatment of HIV-1-infected patients with highly active antiretroviral therapy (HAART) 3 decreases plasma viral load resulting in increase in whole-blood CD4 T cell counts and improvement in CD4:CD8 T cell ratio to normal levels. However, in some HIV-1-infected patients, there is no appreciable increase in CD4 T cell counts or restoration of CD4:CD8 T cell ratio following HAART, despite suppression of plasma viremia for long periods of time (immunological and virological discordance).…”

mentioning

confidence: 99%

Impaired Restoration of Plasmacytoid Dendritic Cells in HIV-1-Infected Patients with Poor CD4 T Cell Reconstitution Is Associated with Decrease in Capacity to Produce IFN-α but Not Proinflammatory Cytokines

Sachdeva

Asthana

Brewer

et al. 2008

The Journal of Immunology

View full text Add to dashboard Cite

We analyzed reconstitution characteristics of plasmacytoid dendritic cells (PDCs) and myeloid DCs-1 in 38 HIV-1-infected patients with impaired restoration of CD4 T cell counts despite prolonged suppression of plasma viremia (discordant) and compared them with 42 patients showing good immunological and virological responses following highly active antiretroviral therapy (HAART). While myeloid DCs showed spontaneous recovery following HAART in both the groups, the discordant patients demonstrated poor peripheral reconstitution of PDCs as compared with concordant patients. The ability of PDCs to produce IFN-α following stimulation with TLR7 ligand imiquimod and TLR9 ligand CpG ODN-2216 was also impaired in discordant patients even after 2 years following initiation of HAART. Lower IFN-α expression in the PDCs following TLR stimulation was further associated with lower expression of transcription factor, IFN regulatory factor-7. In contrast, production of TNF-α and IL-6 following TLR stimulation was comparable in both groups of patients, indicating that impaired reconstitution characteristics do not affect the capacity of PDCs to produce proinflammatory cytokines. The discordant patients had significantly lower baseline CD4 T cell counts and higher baseline viral load at the initiation of HAART implying that lower baseline CD4 T cell counts and higher plasma viral load are associated with impaired restoration of CD4 T cells and PDCs, thus, increasing the susceptibility of discordant patients toward opportunistic infections despite virological control.

show abstract

Incomplete immune reconstitution in HIV/AIDS patients on antiretroviral therapy: Challenges of immunological non-responders

Yang

Zhang

et al. 2020

Journal of Leukocyte Biology

172

196

View full text Add to dashboard Cite

The morbidity and mortality of HIV type‐1 (HIV‐1)‐related diseases were dramatically diminished by the grounds of the introduction of potent antiretroviral therapy, which induces persistent suppression of HIV‐1 replication and gradual recovery of CD4+ T‐cell counts. However, ∼10–40% of HIV‐1‐infected individuals fail to achieve normalization of CD4+ T‐cell counts despite persistent virological suppression. These patients are referred to as “inadequate immunological responders,” “immunodiscordant responders,” or “immunological non‐responders (INRs)” who show severe immunological dysfunction. Indeed, INRs are at an increased risk of clinical progression to AIDS and non‐AIDS events and present higher rates of mortality than HIV‐1‐infected individuals with adequate immune reconstitution. To date, the underlying mechanism of incomplete immune reconstitution in HIV‐1‐infected patients has not been fully elucidated. In light of this limitation, it is of substantial practical significance to deeply understand the mechanism of immune reconstitution and design effective individualized treatment strategies. Therefore, in this review, we aim to highlight the mechanism and risk factors of incomplete immune reconstitution and strategies to intervene.

show abstract

T-cell homeostasis alteration in HIV-1 infected subjects with low CD4 T-cell count despite undetectable virus load during HAART

Abstract: The reduced expression of IL-7Ralpha associated with the persistent immune activation and the alteration of Treg frequencies in part explains the low level of CD4 T cells observed in InR.

Cited by 98 publications

References 48 publications

Association between discordant immunological response to highly active anti-retroviral therapy, regulatory T cell percentage, immune cell activation and very low-level viraemia in HIV-infected patients

Association between discordant immunological response to highly active anti-retroviral therapy, regulatory T cell percentage, immune cell activation and very low-level viraemia in HIV-infected patients

Impaired Restoration of Plasmacytoid Dendritic Cells in HIV-1-Infected Patients with Poor CD4 T Cell Reconstitution Is Associated with Decrease in Capacity to Produce IFN-α but Not Proinflammatory Cytokines

Incomplete immune reconstitution in HIV/AIDS patients on antiretroviral therapy: Challenges of immunological non-responders

Contact Info

Product

Resources

About