IMMUNOPATHOGENESIS OF AND PROSPECTS FOR IMMUNOMODULATORY THERAPY FOR HIV INFECTION Part 2. MEDICAL ISSUES
https://doi.org/10.22328/2077-9828-2017-9-3-7-15
Abstract
Human immunodeficiency virus infection results in decreases counts and compromised functions of T-cells and the associated immunodeficiency, opportunistic infections, and cancer. The paradox of HIV infection is that all this occurs upon the activation of the immune system, mainly inborn immunity, and increased production of cytokines leading to chronic systemic inflamma-tion. The immune response to HIV is evoked immediately upon infection; however, it fails to eliminate HIV, partly because of the active resistance of HIV to host immunity. Antiretroviral therapy is able to suppress HIV replication to a minimum and to somewhat restore the immune system; however, in many patients this is associated with serious complication manifested as the immune reconstitution inflammatory syndrome, IRIS. Immunotherapy for HIV infection is meant to prevent HIV infection and spread by preventive and therapeutic vaccination, including passive vaccination with broad-specificity neutralizing mono-clonal antibodies and the use of anti-chemokine drugs and to restore immunity and to mitigate complications.
About the Author
A. S. Simbirtsev
State Institute of Pure Biological Preparations
Russian Federation
Saint-Petersburg
Russian Federation
Saint-Petersburg
References
1. Maartens G., Celum C., Lewin S. HIV infection: epidemiology, pathogenesis, treatment and prevention. Lancet, 2014, Vol. 384, рр. 258–271.
2. Migueles S., Connors M. Success and failure of the cellular immune response against HIV 1. Nat. Immunol., 2015, Vol. 16, pp. 563–570.
3. Jain V., Hartogensis W., Bacchetti P., Hunt P.W., Hatano H., Sinclair E., Epling L., Lee T.H. Antiretroviral Therapy Initiated Within 6 Months of HIV Infection Is Associated With Lower T-Cell Activation and Smaller HIV Reservoir Size. J. Infect. Dis., 2013, Vol. 208, pp. 1202–1211.
4. Hunt P., Sinclair E., Rodriguez B., Shive C., Clagett B., Funderburg N., Robinson J., Huang Y., Epling L. Gut Epithelial Barrier Dysfunction and Innate Immune Activation Predict Mortality in Treated HIV Infection. J. Infect. Dis., 2014, Vol. 210, pp. 1228–1238.
5. Селимова Л.М., Калнина Л.Б., Серебровская Л.В., Иванова Л.А., Гуляева А.Н., Носик Д.Н. Цитокины при инфекции, вызванной вирусом иммунодефицита человека 1-го типа (ВИЧ-1) // Вопросы вирусологии. 2016. Т. 61, № 1. С. 39–41.[Selimova L.M., Kalnina L.B., Serebrovskaya L.V., Ivanova L.A., Gulyaeva A.N., Nosik D.N. Cytokines in infections caused by human immunodeficiency virus 1 type (HIV-1). Problems of Virology, 2016, Vol. 61, No. 1, pp. 39–41(In Russ.)].
6. Smith C., Ryom L., Weber R., Morlat P., Pradier C., Reiss P., Kowalska J.D., de Wit S., Law M., el Sadr W., Kirk O., Friis-Moller N., Monforte A.D., Phillips A.N., Sabin C.A., Lundgren J.D. Trends in underlying causes of death in people with HIV from 1999 to 2011 (D:A:D): a multicohort collaboration. Lancet, 2014, Vol. 384, pp. 241–248.
7. Lucas S. Causes of death in the HAART era. Curr. Opin. Infect. Dis., 2012, Vol. 25, pp. 36–41.
8. Tenorio A., Zheng Y., Bosch R., Krishnan S., Rodriguez B., Hunt P.W., Plants J. Soluble markers of inflammation and coagulation but not T-cell activation predict non-AIDS-defining morbid events during suppressive antiretroviral treatment. J. Infect. Dis., 2014, Vol. 210, pp. 1248–1259.
9. Lundgren J., Babiker A., Gordin F., Emery S., Grund B., Nordwall J., Quan K., Quan S.F., Schultz T., Sharma S., Thompson G., Lundgren J.D. Initiation of antiretroviral therapy in early asymptomatic HIV infection. N. Engl. J. Med., 2015, Vol. 373, pp. 795–807.
10. French M., Lenzo N., John N., Mallal S.A., McKinnon E.J., James I.R., Price P. Immune restoration disease after the treatment of immunodefi- cient HIV-infected patients with highly active antiretroviral therapy. HIV Med., 2005, Vol. 1, pp. 107–115.
11. Hsu D., Sereti I. Serious Non-AIDS Events: Therapeutic Targets of Immune Activation and Chronic Inflammation in HIV Infection. Drugs, 2016, Vol. 76, pp. 533–549.
12. Bandera A., Colella E., Rizzardini G., Gori A., Clerici M. Strategies to limit Immune-activation in HIV patients. Expert Rev. Anti-Infect. Ther., 2016, Vol. 4, pp. 1–12.
13. Rerks-Ngarm S., Pitisuttithum P., Nitayaphan S., Kaewkungwal J., Chiu J. Vaccination with ALVAC and AIDSVAX to prevent HIV-1 infection in Thailand. N. Engl. J. Med., 2009, Vol. 361, pp. 2209–2220.
14. Haynes B., Gilbert P., McElrath M., Zolla-Pazner S., Tomaras G.D., Munir Alam S., Evans D.T., Montefiori D.C., Chitraporn Karnasuta, Sutthent R., Liao H.X., DeVico A.L., Lewis G.K., Williams Constance, Pinter A., Fong Y., Janes H., DeCamp A., Huang Y., Rao M., Billings E., Karasavvas N. Immune-correlates analysis of an HIV-1 vaccine efficacy trial. N. Engl. J. Med., 2012, Vol. 366, pp. 1275–1286.
15. Gray G., Laher F., Lazarus E., Ensoli B., Corey L. Approaches to preventative and therapeutic HIV vaccines. Curr. Opin. Virol., 2016, Vol. 17, pp. 104–109.
16. Ho D., Hartshorn K., Rota T., Andrews C.A., Kaplan J.C., Schooley R.T., Hirsch M.S. Recombinant human interferon alfa-A suppresses HTLV-III replication in vitro. Lancet, 1985, Vol. 1 (8429), pp. 602–604.
17. Rivero J., Fraga M., Cancio I., Cuervo J., Lopez-Saura I.P., Sanatorio I. Long-term treatment with recombinant interferon alpha-2b prolongs survival of asymptomatic HIV-infected individuals. Biotherapy, 1997, Vol. 10, pp. 107–113.
18. Lane H., Kovacs J., Feinberg J. Anti-retroviral effects of interferon-alpha in AIDS-associated Kaposi’s sarcoma. Lancet, 1988, Vol. 2 (8622), pp. 1218–1222.
19. Asmuth D., Utay N., Pollard R. Peginterferon α-2a for the treatment of HIV infection. Expert Opin. Investig. Drugs, 2016, Vol. 25, pp. 249–257.
20. Abrams D., Levy Y., Losso M., Babiker A., Collins G., Cooper D.A., Darbyshire J. Interleukin-2 therapy in patients with HIV infection. New Engl. J. Med., 2009, Vol. 361, pp. 1548–1559.
21. Markowitz N., Lopardo G., Wentworth D., Gey D., Babiker A., Fox L. Long-Term Effects of Intermittent IL-2 in HIV Infection: Extended Follow-Up of the INSIGHT STALWART Study. PLoS One, 2012, Vol. 7, pp. e47506.
22. Chahroudi A., Silvestri G. Interleukin-7 in HIV pathogenesis and therapy. Eur. Cytokine Netw., 2010, Vol. 21, pp. 202–207.
23. Levy Y., Lacabaratz C., Weiss L., Viard J.P., Goujard C., Lelievre J.D. Enhanced T cell recovery in HIV-1-infected adults through IL-7 treatment. J. Clin. Invest., 2009, Vol. 119, pp. 997–1007.
24. Coiras M., Bermejo M., Descours B., Mateos E., García-Pérez J., Alcamí J. IL-7 Induces SAMHD1 Phosphorylation in CD4+ T Lymphocytes, Improving Early Steps of HIV-1 Life Cycle. J. Cell. Rep., 2016, Vol. 14, pp. 2100–2107.
25. Crawley A., Angel J. The influence of HIV on CD127 expression and its potential implications for IL-7 therapy. Semin. Immunol., 2012, Vol. 24, pp. 231–240.
26. Nguyen T.P., Shukla S., Asaad R., Freeman M.L., Lederman M.M., Harding C.V., Sieg S.F. Responsiveness to IL-7but not to IFN- is diminished in CD4+ T cells from treated HIV infected patients who experience poor CD4+ T-cell recovery. AIDS, 2016, Aug. 24, Vol. 30 (13), pp. 2033–2042.
27. Katlama C., Lambert-Niclot S., Assoumou L., Papagno L., Lecardonnel F., Zoorob R. Treatment intensification followed by interleukin-7 reactivates HIV without reducing total HIV DNA: a randomized trial. AIDS, 2016, Vol. 30, pp. 221–230.
28. Napolitano L., Schmidt D., Gotway M., Ameli N., Filbert E.L., Ng M.M. Growth hormone enhances thymic function in HIV-1-infected adults. J. Clin. Invest., 2008, Vol. 118, pp. 1085–1098.
29. Lindboe J., Langkilde A., Eugen-Olsen J., Hansen B.R., Haupt T.H. Low-dose growth hormone therapy reduces inflammation in HIV-infected patients: a randomized placebo-controlled study. Infect. Dis., 2016, Vol. 48, pp. 829–837.
30. Herasimtschuk A., Downey J., Nelson M., Moyle G., Mandalia S., Sikut R., Gotch F., Imami N. Therapeutic immunisation plus cytokine and hormone therapy improves CD4 T-cell counts, restores anti-HIV-1 responses and reduces immune activation in treated chronic HIV-1 infection. Vaccine, 2014, Vol. 32, pp. 7005–7013.
31. Van Der Ryst E. Maraviroc — A CCR5 Antagonist for the Treatment of HIV-1 Infection. Front. Immunol., 2015, Vol. 6, pp. 277–284.
32. Serrano-Villar S., Sainz T., Ma Z., Utay N.S., Wook-Chun T., Mann S. Effects of Combined CCR5/Integrase Inhibitors-Based Regimen on Mucosal Immunity in HIV-Infected Patients Naïve to Antiretroviral Therapy: A Pilot Randomized Trial. PLoS Pathog., 2016, Vol. 12, pp. e1005381.
Review
For citations:
Simbirtsev A.S. IMMUNOPATHOGENESIS OF AND PROSPECTS FOR IMMUNOMODULATORY THERAPY FOR HIV INFECTION Part 2. MEDICAL ISSUES. HIV Infection and Immunosuppressive Disorders. 2017;9(3):7-15. (In Russ.) https://doi.org/10.22328/2077-9828-2017-9-3-7-15
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