HCV-coinfection is Related to an Increased HIV-1 Reservoir Size in CART-treated HIV Patients: a Cross-sectional Study

Overview

Journal Sci Rep

Specialty Science

Date 2019 Apr 5

PMID 30944340

Citations 19

Authors

Maria Rosa Lopez-Huertas

Claudia Palladino

Marta Garrido-Arquero

Beatriz Esteban-Cartelle

Marta Sanchez-Carrillo

Paula Martinez-Roman

Luz Martin-Carbonero

Pablo Ryan

Lourdes Dominguez-Dominguez

Ignacio de Los Santos

Sara de la Fuente Moral

Jose Miguel Benito

Norma Rallon

Jose Alcami

Salvador Resino

Amanda Fernandez-Rodriguez

Mayte Coiras

Veronica Briz

Affiliations

Soon will be listed here.

Abstract

In HIV-1/HCV-coinfected patients, chronic HCV infection leads to an increased T-lymphocyte immune activation compared to HIV-monoinfected patients, thereby likely contributing to increase HIV-1 reservoir that is the major barrier for its eradication. Our objective was to evaluate the influence of HCV coinfection in HIV-1 viral reservoir size in resting (r) CD4+ T-cells (CD25-CD69-HLADR-). Multicenter cross-sectional study of 97 cART-treated HIV-1 patients, including 36 patients with HIV and HCV-chronic co-infection without anti-HCV treatment, 32 HIV patients with HCV spontaneous clearance and 29 HIV-monoinfected patients. rCD4+ T-cells were isolated and total DNA was extracted. HIV viral reservoir was measured by Alu-LTR qPCR. Differences between groups were calculated with a generalized linear model. Overall, 63.9% were men, median age of 41 years and Caucasian. Median CD4+ and CD8+ T-lymphocytes were 725 and 858 cells/mm, respectively. CD4+ T nadir cells was 305 cells/mm. Proviral HIV-1 DNA size was significantly increased in chronic HIV/HCV-coinfected compared to HIV-monoinfected patients (206.21 ± 47.38 vs. 87.34 ± 22.46, respectively; P = 0.009), as well as in spontaneously clarified HCV co-infected patients when compared to HIV-monoinfected individuals (136.20 ± 33.20; P = 0.009). HIV-1/HCV co-infected patients showed a larger HIV-1 reservoir size in comparison to HIV-monoinfected individuals. This increase could lead to a greater complexity in the elimination of HIV-1 reservoir in HIV-1/HCV-coinfected individuals, which should be considered in the current strategies for the elimination of HIV-1 reservoir.

Citing Articles

The Proviral Reservoirs of Human Immunodeficiency Virus (HIV) Infection.

Murzin A, Elfimov K, Gashnikova N Pathogens. 2025; 14(1).

PMID: 39860976 PMC: 11768375. DOI: 10.3390/pathogens14010015.

The Era of DAAs: Assessing the Patients' Characteristics, Clinical Impact, and Emergence of Comorbidities in HIV/HCV-Coinfected versus HIV-Infected Individuals.

Alvarez-Alvarez B, Prieto-Perez L, De la Cuadra-Grande A, Casado M, Cabello Ubeda A, Al-Hayani A J Clin Med. 2024; 13(13).

PMID: 38999501 PMC: 11242478. DOI: 10.3390/jcm13133936.

Interferon-Regulated Expression of Cellular Splicing Factors Modulates Multiple Levels of HIV-1 Gene Expression and Replication.

Roesmann F, Muller L, Klaassen K, Hess S, Widera M Viruses. 2024; 16(6).

PMID: 38932230 PMC: 11209495. DOI: 10.3390/v16060938.

HIV-Infected Hepatic Stellate Cells or HCV-Infected Hepatocytes Are Unable to Promote Latency Reversal among HIV-Infected Mononuclear Cells.

Lopez C, Freiberger R, Sviercz F, Quarleri J, Delpino M Pathogens. 2024; 13(2).

PMID: 38392872 PMC: 10893349. DOI: 10.3390/pathogens13020134.

DAA-mediated HCV cure reduces HIV DNA levels in HCV/HIV coinfected people.

Gobran S, Pagliuzza A, Khedr O, Fert A, Chomont N, Bruneau J J Virol. 2023; 97(12):e0110523.

PMID: 38051044 PMC: 10734513. DOI: 10.1128/jvi.01105-23.

References

Maldarelli F . HIV-infected cells are frequently clonally expanded after prolonged antiretroviral therapy: implications for HIV persistence. J Virus Erad. 2016; 1(4):237-44. PMC: 4946654. View

Liu C, Ma X, Liu B, Chen C, Zhang H . HIV-1 functional cure: will the dream come true?. BMC Med. 2015; 13:284. PMC: 4654816. DOI: 10.1186/s12916-015-0517-y. View

Buzon M, Sun H, Li C, Shaw A, Seiss K, Ouyang Z . HIV-1 persistence in CD4+ T cells with stem cell-like properties. Nat Med. 2014; 20(2):139-42. PMC: 3959167. DOI: 10.1038/nm.3445. View

Darcis G, Bouchat S, Kula A, Van Driessche B, Delacourt N, Vanhulle C . Reactivation capacity by latency-reversing agents ex vivo correlates with the size of the HIV-1 reservoir. AIDS. 2016; 31(2):181-189. DOI: 10.1097/QAD.0000000000001290. View

Li K, Lemon S . Innate immune responses in hepatitis C virus infection. Semin Immunopathol. 2012; 35(1):53-72. PMC: 3732459. DOI: 10.1007/s00281-012-0332-x. View

Kiselinova M, De Spiegelaere W, Buzon M, Malatinkova E, Lichterfeld M, Vandekerckhove L . Integrated and Total HIV-1 DNA Predict Ex Vivo Viral Outgrowth. PLoS Pathog. 2016; 12(3):e1005472. PMC: 4777389. DOI: 10.1371/journal.ppat.1005472. View

Kim S, Oh H, Wanless I, Lee S, Han K, Park Y . The Laennec staging system for histological sub-classification of cirrhosis is useful for stratification of prognosis in patients with liver cirrhosis. J Hepatol. 2012; 57(3):556-63. DOI: 10.1016/j.jhep.2012.04.029. View

Chavez L, Calvanese V, Verdin E . HIV Latency Is Established Directly and Early in Both Resting and Activated Primary CD4 T Cells. PLoS Pathog. 2015; 11(6):e1004955. PMC: 4466167. DOI: 10.1371/journal.ppat.1004955. View

Bergqvist A, Sundstrom S, Dimberg L, Gylfe E, Masucci M . The hepatitis C virus core protein modulates T cell responses by inducing spontaneous and altering T-cell receptor-triggered Ca2+ oscillations. J Biol Chem. 2003; 278(21):18877-83. DOI: 10.1074/jbc.M300185200. View

10.

Goletti D, Weissman D, Jackson R, Graham N, Vlahov D, Klein R . Effect of Mycobacterium tuberculosis on HIV replication. Role of immune activation. J Immunol. 1996; 157(3):1271-8. View

11.

Bergqvist A, Rice C . Transcriptional activation of the interleukin-2 promoter by hepatitis C virus core protein. J Virol. 2001; 75(2):772-81. PMC: 113973. DOI: 10.1128/JVI.75.2.772-781.2001. View

12.

Kerzerho J, McIlvaine E, Anthony P, Mack W, Wang C, Frederick T . Impact of Hepatitis C Virus on the Circulating Levels of IL-7 in HIV-1 Coinfected Women. J Acquir Immune Defic Syndr. 2016; 71(2):172-80. PMC: 4712709. DOI: 10.1097/QAI.0000000000000832. View

13.

Lee S, Sinclair E, Hatano H, Hsue P, Epling L, Hecht F . Impact of HIV on CD8+ T cell CD57 expression is distinct from that of CMV and aging. PLoS One. 2014; 9(2):e89444. PMC: 3937334. DOI: 10.1371/journal.pone.0089444. View

14.

Hosmane N, Kwon K, Bruner K, Capoferri A, Beg S, Rosenbloom D . Proliferation of latently infected CD4 T cells carrying replication-competent HIV-1: Potential role in latent reservoir dynamics. J Exp Med. 2017; 214(4):959-972. PMC: 5379987. DOI: 10.1084/jem.20170193. View

15.

Platt L, Easterbrook P, Gower E, McDonald B, Sabin K, McGowan C . Prevalence and burden of HCV co-infection in people living with HIV: a global systematic review and meta-analysis. Lancet Infect Dis. 2016; 16(7):797-808. DOI: 10.1016/S1473-3099(15)00485-5. View

16.

Masia M, Robledano C, Ortiz de la Tabla V, Antequera P, Lumbreras B, Hernandez I . Coinfection with human herpesvirus 8 is associated with persistent inflammation and immune activation in virologically suppressed HIV-infected patients. PLoS One. 2014; 9(8):e105442. PMC: 4136871. DOI: 10.1371/journal.pone.0105442. View

17.

Moron-Lopez S, Gomez-Mora E, Salgado M, Ouchi D, Puertas M, Urrea V . Short-term Treatment With Interferon Alfa Diminishes Expression of HIV-1 and Reduces CD4+ T-Cell Activation in Patients Coinfected With HIV and Hepatitis C Virus and Receiving Antiretroviral Therapy. J Infect Dis. 2015; 213(6):1008-12. PMC: 4760418. DOI: 10.1093/infdis/jiv521. View

18.

Blackard J, Smeaton L, Hiasa Y, Horiike N, Onji M, Jamieson D . Detection of hepatitis C virus (HCV) in serum and peripheral-blood mononuclear cells from HCV-monoinfected and HIV/HCV-coinfected persons. J Infect Dis. 2005; 192(2):258-65. DOI: 10.1086/430949. View

19.

Whitney J, Hill A, Sanisetty S, Penaloza-MacMaster P, Liu J, Shetty M . Rapid seeding of the viral reservoir prior to SIV viraemia in rhesus monkeys. Nature. 2014; 512(7512):74-7. PMC: 4126858. DOI: 10.1038/nature13594. View

20.

Chomont N, El-Far M, Ancuta P, Trautmann L, Procopio F, Yassine-Diab B . HIV reservoir size and persistence are driven by T cell survival and homeostatic proliferation. Nat Med. 2009; 15(8):893-900. PMC: 2859814. DOI: 10.1038/nm.1972. View