Medical Pharmacology: Antiviral Drugs

**HIV-1 Infection: CD4+ T Cell Reactivation⁹**

"HIV-1 infects activated CD4⁺ T cells, which have increased nucleotide pools, cytokines, and transcription factors compared to nonactivated cells. "Most of these infected cells die due to cytopathic effects of the virus or lysis by HIV-specific CTLs.* "Cells that revert back to a resting memory T cell survive and may undergo homeostatic proliferation. "Upon initiation of ART, these latently infected cells persist. "However, treatment of these cells with reactivating agents causes the cells to actively produce virus and ultimately leads to either spontaneous cell death or death through immune system clearance." CTLs: HIV-specific cytotoxic T lymphocytes *ART: Active Retroviral Treatment Figure Attribution: Figure 1 from reference 9 (Ruelas DS Greene WC An Integrated Overview of HIV-1 Latency (Leading Edge Review) Cell 155: 519-529 October 24, 2013)

References
Flexner C Antiretroviral Agents and Treatment of HIV Infection, Chapter 59 in Goodman & Gilman's The Pharmacological Basis of Therapeutics, 12th edition (Brunton LL Chabner BA Knollmann BC, eds; Brunton LL, ed; Blumenthal DK Murri N Hilal-Dandan R, assoc eds, Knollmann BC, consulting ed, on-line edition) The McGraw-Hill Companies, 2011. Fauci AS Lane HC Chapter 189, Human Immunodeficiency Virus Disease: AIDS and Related Disorders, in Harrison's Online (Dan L. Longo, Anthony S. Fauci, Dennis L. Kasper, Stephen L. Hauser, J. Larry Jameson, Joseph Loscalzo, Eds.), Harrison's Principles of Internal Medicine, 18th edition, The McGraw-Hill Companies, Inc. 2012. Longo DL Fauci AS 188, The Human Retroviruses, in Harrison's Online (Dan L. Longo, Anthony S. Fauci, Dennis L. Kasper, Stephen L. Hauser, J. Larry Jameson, Joseph Loscalzo, Eds.), Harrison's Principles of Internal Medicine, 18th edition, The McGraw-Hill Companies, Inc. 2012. Safrin S Antiviral Agents, Chapter 49 in Basic & Clinical Pharmacology, 12 e (Katzung BG Masters SB Trevor AJ) The McGraw-Hill Companies, 2012 (on-line edition). Cochrane A Retroviruses Chapter 28 in Fundaments of Molecular Virology, 2e, Acheson NH, ed., John Wiley & Sons pp 342-353 2011. Cochrane A Human Immunodeficiency Virus Chapter 29 in Fundaments of Molecular Virology, 2e, Acheson NH, ed., John Wiley & Sons pp 354-364 2011. Ryan KJ, Ray C. Chapter 18. Retroviruses: Human T-Lymphotropic Virus, Human Immunodeficiency Virus, and Acquired Immunodeficiency Syndrome. In: Ryan KJ, Ray C. eds. Sherris Medical Microbiology (Part editor, Ahmad N Ray CG Drew WL), 5e. New York, NY: McGraw-Hill; 2010. Butel JS Chapter 44: AIDS and Lentiviruses (Brooks FG, Carroll KC Butel JS Morse SA, Mietzner TA in Jawetz, Melnick & Adelberg's Medical Microbiology, 26th edition), 2013, on-line edition. Ruelas DS Greene WC An Integrated Overview of HIV-1 Latency (Leading Edge Review) Cell 155: 519-529 October 24, 2013 Chun TW Engel D Berrey MM Shea T Corey L Fauci AS. Early establishment of a pool of latently infected resting CD4(+) T cells during primary HIV-1 infection. Proc. Natl Acad Sci USA 95, 8869-8873 1998. Wong JK Hezareh M Gunthard HF Havlir DV Ignacio CC Spina CA Richman DD Recovery of replication-competent HIV despite prolonged supression of plasma viremia. Science 278, 1291-11295, 1997. (second sourced from reference 9) Chun TW Stuyver L Mizell SB Ehler LA Mican JA Baselar M Lloyd AL Nowak MA Fauci AS Presence of an inducible HIV-1 latant reservoir during highly active antiretroviral therapy. Proc Natl Acad Sci USA 94: 13193-13197 1997. (second sourced from reference 9) Finzi D Hermankova M Pierson T Carruth LM Buck C Chaisson RE Quinn TC Chadwick K Margolick J Brookmeyer R Gallant J Markowitz M Ho DD Richman DD Siliciano RF Identification of a reservoir for HIV-1 in patients on highly active antiretroviral therapy Science 278(5341): 1295-1300, Nov 14, 1997. (second sourced from reference 9) Ho Y-C Shan L Hosmane NN Wang J Laskey SB Rosenbloom DIS Lai J Blankson JN Siliciano JD Siliciano RF Replication-Competent Noninduced Proviruses in the Latent Reservoir Increase Barrier to HIV-1 Cure. Cell 155, 540-551, October 24, 2013.

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