Nursing Pharmacology:  Antiviral Drugs

• Antiviral Drugs

  • Anti-viral drugs with activity against HIV (Human Immunodeficiency Virus)

    • HIV-1 Pathophysiology/Pathogenesis:  HIV Disease Presentations

      Renal Dysfunction

      • Kidney disease may occur as a:

        • Direct result of infection with HIV²

          • HIV-1 has been demonstrated in clinical and animal studies to infect renal parenchymal cells in HIVAN (HIV-associated neuropathy).⁵ 

            • HIV DNA and mRNA have been demonstrated in human renal tissue. Local renal viral replication has been shown.

              • An HIV viral reservoir may include renal epithelium.

              • HIV appears to enter renal epithelial cells without depending on CD4⁺ or other currently identified HIV coreceptors.

                • One study involving T cells fluorescently labeled with HIV virus and exposed to renal tubular epithelial cells found direct viral intercellular transfer.

                • Such transfer did not require CD4⁺ but was dependent on cell-cell adhesion.

                  • Following viral internalization, HIV-specific proteins were synthesized.⁵ 

            • Although evidence that HIV1 might infect kidney cells in HIVAN, definitive data supporting renal epithelial cell HIV-1 infection was presented in 2000.⁹ 

              • Early on, patients with HIV disease affecting the kidney exhibited rapid progression to end-stage renal disease and death.

                • However, more attention was focused on AIDS-defining opportunistic infections along with malignancies during the first decade of the HIV epidemic.⁹ 

              • In 2000, investigators utilized three methods which confirmed HIV-1 in human kidney tissue.¹⁰ 

        • Indirectly renal pathology was inferred as a result of opportunistic infection or neoplasm.² 

          • Furthermore, drug toxicity may also result in renal dysfunction.² 

      • Microalbuminuria is noted in about 20% of untreated HIV-infected individuals and significant proteinuria is seen in about 2% of untreated HIV patients.² 

        • Microalbuminuria appears indicative of an increased mortality rate, due to all causes. 

        • HIV-associated neuropathy (HIVAN) has been identified as a direct HIV-infection complication and may be noted as an early indicator of HIV infection.² 

          • HIV-associated neuropathy (HIVAN)⁶

            (A, left image):  "HIV-associated nephropathy (HIVAN) with collapsed glomerulli, characteristic microcystic transformation of renal tubules, and concomitant interstitial inflammation and fibrosis." (B, right image):  "High-power view of collapsing glomerulopathy in a case of HIVAN with collapse of glomerular capillary structures and striking hyperplasia of podocytes." "Magnifications:  x100 in A; x400 in B (Jones methenamine silver stain in both." http://cjasn.asnjournals.org/content/2/Supplement_1/S6/F1.expansion (2015)

          •  

            "Tubuloreticular Structures in Glomerular Endothelial Cells"⁸

            "The electron microscopy image was acquired from a renal biopsy specimen of a patient \with HIV-associated nephropathy (HIVAN), original magnification x16000" (Dikman S, Department of Pathology, Mt Sinai Hospital, New York, NY, USA). Image corresponds to Figure 2 in reference 8. Anders H-J Lichtnekert J Allam R Interferon-α and -β in kidney inflammation.  Mini-Review:  Kidney International 77:  848-854, 2010. http://www.nature.com/ki/journal/v77/n10/full/ki201071a.html

          • Most of the time, however, HIV-associated neuropathy (HIVAN) is found in patients who exhibit a CD4⁺ T cell counts of <200/µL.

            • HIVAN may also occur in children.²

          • The majority of  HIVAN cases, >90%, occur in African-American or Hispanic patients and is a more severe in this population.²

          • cART administration (HAART, highly active antiretroviral treatment) seems to decrease the rate of progression to end-stage renal disease.^2,5

            • Also, individuals with HIVAN should be treated for HIV infection independent of specific CD4⁺ T cell levels.

            • Other agents which may be beneficial include ACE inhibitors (angiotensin-converting enzyme inhibitors) and/or prednisone.^2,5

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. Woster PM Chapter 43:  Antiviral Agents and Protease Inhibitors in Foye's Principles of Medicinal Chemistry 6e, Lemke, TL Williams DA, eds; Roche VG Zito SW, asst eds) Wolters Kluwer|Lippincott Williams & Wilkins 1214, 2008. Mariani  LH Berns JS Chapter 28, Viral Nephropathies in National Kidney Foundation Primer on Kidney Diseasesa 6e (Gilbert SJ Weiner DE, eds) 2014. Emerging Paradigms in the Renal Pathology of Viral Diseases,  Clinical Journal of the American Society of Nephrology.  http://cjasn.asnjournals.org/content/2/Supplement_1/S6/F1.expansion Popik W Molecular Mechanisms of HIVAN Pathogenesis, RCMI Translational Research Network http://www2.rtrn.net/my-product/rcmi-spotlight-presents-meharry-medical-college-molecular-mechanisms-of-hivan-pathogenesis/ Anders H-J Lichtnekert J Allam R Interferon-α and -β in kidney inflammation.  Mini-Review:  Kidney International 77:  848-854, 2010. http://www.nature.com/ki/journal/v77/n10/full/ki201071a.html Wyatt CM Klotman PE HIV-1 and HIV-Associated Nephropathy 25 Years Later.  Clin J Am Soc Nephrol 2:  S20-S24, 2007 Bruggeman LA Ross MD Tanji N Cara A Sikman S Gordon RE Burns GC D'Agati VD Winston JA Klotman ME Klotman PE  Renal Epithelium Is a Previously Unrecognized Site of HIV-1 Infection.  J Am Soc Nephrol 11:  2079-2087, 2000.

 

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