Influence of hepatitis C virus coinfection on CD4+ T cells of HIV-infected patients receiving HAART

Shmagel, K. V.; Сайдакова, Е. В.; Korolevskaya, L. B.; Shmagel, N. G.; Chereshnev, V. А.; Anthony, Donald D.; Lederman, Michael M.

doi:10.1097/qad.0000000000000418

Cited by 27 publications

(27 citation statements)

References 30 publications

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“…Our study confirms several prior studies that found an association between HIV/HCV co-infection and a reduced immunologic, but not virologic, response to ART, [3][4][5][6][7][8][9] as well as studies demonstrating improved immunologic response among women compared with men. [20][21][22][23][24] Similar to the findings of a recent meta-analysis by Tsiara et al, 5 Int, p value for interaction across sex strata.…”

Section: Discussionsupporting

confidence: 93%

“…1,2 HIV/ HCV co-infection may also reduce the response to antiretroviral therapy (ART), [3][4][5][6][7][8][9] and ultimately increase the risk of mortality among HIV-infected individuals. [10][11][12] HIV/ HCV-co-infected individuals are considered a priority population for HCV treatment due to more rapid liver disease progression in the setting of HIV infection.…”

Section: Introductionmentioning

confidence: 99%

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Differences in Response to Antiretroviral Therapy by Sex and Hepatitis C Infection Status

Marcus

Leyden

Chao

et al. 2015

AIDS Patient Care and STDs

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Hepatitis C virus (HCV) co-infection and biological sex may each affect response to antiretroviral therapy (ART), yet no studies have examined HIV-associated outcomes by both HCV status and sex. We conducted a cohort study of HIV-infected adults initiating ART in Kaiser Permanente California during 1996-2011. We used piecewise linear regression to assess CD4 changes by sex and HCV status over 5 years. We used Cox regression to estimate hazard ratios (HR) by sex and HCV status for HIV RNA <500 copies/mL over 1 year, and for AIDS and death over the follow-up period. Among 12,865 subjects, there were 154 HIV/HCV-co-infected women, 1000 HIV/HCV-co-infected men, 1088 HIV-mono-infected women, and 10,623 HIV-mono-infected men. CD4 increases were slower in the first year for HIV/HCV-co-infected women (75 cells/μL) and men (70 cells/μL) compared with HIV-mono-infected women (145 cells/μL) and men (120 cells/μL; p<0.001). After 5 years, women had higher CD4 than men in both HIV-mono-infected (598 vs. 562 cells/μL, p=0.003) and HIV/HCV-co-infected individuals (567 vs. 509 cells/μL, p=0.003). Regardless of sex, HIV/HCV co-infection was associated with 40% higher mortality [95% confidence interval (CI): 1.2-1.6] compared with HIV mono-infection, but was not associated with AIDS (HR 1.1, 95% CI: 0.9-1.3) or achieving HIV RNA <500 copies/mL (HR 1.0, 95% CI: 0.9-1.1). HIV/HCV-co-infected men and women have slower CD4 recovery after starting ART and have increased mortality compared with HIV-mono-infected men and women. HCV should be aggressively treated in HIV/HCV-co-infected adults, regardless of sex.

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Section: Discussionsupporting

confidence: 93%

Section: Introductionmentioning

confidence: 99%

Differences in Response to Antiretroviral Therapy by Sex and Hepatitis C Infection Status

Marcus

Leyden

Chao

et al. 2015

AIDS Patient Care and STDs

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“…Previous studies have reported increased apoptosis in total [58, 103, 104] and in T CM [58, 105] CD4 T cells from patients with HIV, which is an explanation of CD4 T cell loss in chronic infection [106]. These and other studies [13, 57–60] inferred apoptosis by demonstrating Annexin V binding to viable cells; however, it has been demonstrated that Annexin V binding can be increased in other cell death pathways [107–110]. In this regard, we found that HIV infection altered the expression of a considerable number of genes that indicated that apoptosis would not be favored.…”

Section: Discussionmentioning

confidence: 68%

“…Since the predictions of increased proliferation and increased cytostasis were incompatible, and the prediction of reduced apoptosis did not agree with previous evidence [13, 57–60], we took into account that enrichment tools base their predictions on a broad set of previous findings, ranging from very particular to very general ones. Accordingly, we investigated if the predictions were based on more demarcated processes, and if these processes were compatible.…”

Section: Resultsmentioning

confidence: 99%

A transcriptome-based model of central memory CD4 T cell death in HIV infection

et al. 2016

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BackgroundHuman central memory CD4 T cells are characterized by their capacity of proliferation and differentiation into effector memory CD4 T cells. Homeostasis of central memory CD4 T cells is considered a key factor sustaining the asymptomatic stage of Human Immunodeficiency Virus type 1 (HIV-1) infection, while progression to acquired immunodeficiency syndrome is imputed to central memory CD4 T cells homeostatic failure. We investigated if central memory CD4 T cells from patients with HIV-1 infection have a gene expression profile impeding proliferation and survival, despite their activated state.MethodsUsing gene expression microarrays, we analyzed mRNA expression patterns in naive, central memory, and effector memory CD4 T cells from healthy controls, and naive and central memory CD4 T cells from patients with HIV-1 infection. Differentially expressed genes, defined by Log2 Fold Change (FC) ≥ |0.5| and Log (odds) > 0, were used in pathway enrichment analyses.ResultsCentral memory CD4 T cells from patients and controls showed comparable expression of differentiation-related genes, ruling out an effector-like differentiation of central memory CD4 T cells in HIV infection. However, 210 genes were differentially expressed in central memory CD4 T cells from patients compared with those from controls. Expression of 75 of these genes was validated by semi quantitative RT-PCR, and independently reproduced enrichment results from this gene expression signature. The results of functional enrichment analysis indicated movement to cell cycle phases G1 and S (increased CCNE1, MKI67, IL12RB2, ADAM9, decreased FGF9, etc.), but also arrest in G2/M (increased CHK1, RBBP8, KIF11, etc.). Unexpectedly, the results also suggested decreased apoptosis (increased CSTA, NFKBIA, decreased RNASEL, etc.). Results also suggested increased IL-1β, IFN-γ, TNF, and RANTES (CCR5) activity upstream of the central memory CD4 T cells signature, consistent with the demonstrated milieu in HIV infection.ConclusionsOur findings support a model where progressive loss of central memory CD4 T cells in chronic HIV-1 infection is driven by increased cell cycle entry followed by mitotic arrest, leading to a non-apoptotic death pathway without actual proliferation, possibly contributing to increased turnover.Electronic supplementary materialThe online version of this article (doi:10.1186/s12864-016-3308-8) contains supplementary material, which is available to authorized users.

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“…However, in our study the levels of activated CD8 + T cells, evaluated as the simultaneous expression of HLA-DR and CD38, were similar in coinfected and monoinfected subjects, with significant differences found only in the CD4 + T cell subset. 24 Indeed, these higher levels of HLA-DR + CD38 + CD4 + T cells among coinfected patients were closely correlated with lower CD4 + T cell counts and, thus, with the CD4:CD8 ratio. Moreover, the correlation between the levels of HLA-DR +-CD38 + CD8 + T cells and sCD14 suggests a link between innate and adaptive immune activation among HIV/HCV-coinfected individuals.…”

Section: Discussionmentioning

confidence: 97%

Higher Activation in CD4⁺ T Cells But Similar Viral Control Among HIV/Hepatitis C Virus-Coinfected Patients on a Simplification Monotherapy

BenMarzouk-Hidalgo

Torres-Cornejo

Gutiérrez‐Valencia

et al. 2016

AIDS Research and Human Retroviruses

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The aim of this study was to assess whether hepatitis C virus (HCV) coinfection would affect the clinical and immunological outcome of HIV-infected patients following a simplification strategy. A prospective cohort of HIV-infected patients starting a ritonavir boosted darunavir monotherapy (mtDRV/rtv) was followed for 24 months. HCV infection was evaluated by HCV viremia and hepatic fibrosis. Immune activation was studied as HLA-DR CD38 coexpression on CD4(+) and CD8(+) T cells and also the quantification of plasma sCD14 levels. Microbial translocation was studied by the plasma levels of 16S rDNA and lipopolysaccharide (LPS). A total of 150 HIV-infected patients were enrolled in this study, including 46 individuals also infected with HCV (30.6%). HIV/HCV coinfection did not decrease mtDRV/rtv efficacy, since similar rates of HIV-1 intermittent viremia (HCV: 26.6% vs. no-HCV: 34.7%) and episodes of virological failure (HCV: 22.2% vs. no-HCV: 11.2%, p-value = 0.381) were found. No major differences were found between both groups at baseline, although higher HLA-DR(+)CD38(+)CD4(+) T cell counts were found in the coinfected group (HCV: 6.65% vs. no-HCV: 4.55%, p-value = 0.032); this difference was maintained in the 24 months of follow-up. After the 24-month follow-up, both groups, HIV-monoinfected patients and HIV/HCV-coinfected patients, presented similar immune activation and microbial translocation profiles. In conclusion, the use of a simplified mtDRV/rtv strategy compromises neither HIV nor HCV viremic control in coinfected patients, although a higher immune activation of CD4(+) T cells was found.

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Influence of hepatitis C virus coinfection on CD4+ T cells of HIV-infected patients receiving HAART

Abstract: Whereas we could find no relationship between HCV infection and most indices of CD4⁺ T-cell homeostasis or activation, CD4⁺ RTEs are diminished in the circulation of HCV coinfected persons and appear to be related to indices of ongoing hepatic damage or inflammation.

Cited by 27 publications

References 30 publications

Differences in Response to Antiretroviral Therapy by Sex and Hepatitis C Infection Status

Differences in Response to Antiretroviral Therapy by Sex and Hepatitis C Infection Status

A transcriptome-based model of central memory CD4 T cell death in HIV infection

Higher Activation in CD4⁺ T Cells But Similar Viral Control Among HIV/Hepatitis C Virus-Coinfected Patients on a Simplification Monotherapy

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Influence of hepatitis C virus coinfection on CD4+ T cells of HIV-infected patients receiving HAART

Abstract: Whereas we could find no relationship between HCV infection and most indices of CD4⁺ T-cell homeostasis or activation, CD4⁺ RTEs are diminished in the circulation of HCV coinfected persons and appear to be related to indices of ongoing hepatic damage or inflammation.

Cited by 27 publications

References 30 publications

Differences in Response to Antiretroviral Therapy by Sex and Hepatitis C Infection Status

Differences in Response to Antiretroviral Therapy by Sex and Hepatitis C Infection Status

A transcriptome-based model of central memory CD4 T cell death in HIV infection

Higher Activation in CD4+ T Cells But Similar Viral Control Among HIV/Hepatitis C Virus-Coinfected Patients on a Simplification Monotherapy

Contact Info

Product

Resources

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Higher Activation in CD4⁺ T Cells But Similar Viral Control Among HIV/Hepatitis C Virus-Coinfected Patients on a Simplification Monotherapy