Nursing Pharmacology:  Antiviral Drugs

• Antiviral Drugs

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

    • HIV-1 Pathophysiology/Pathogenesis:  HIV Disease Presentations

      • Cardiovascular Diseases

        • Heart disease has been identified in about 40% of autopsy cases (25%-75% considering various autopsy series) in HIV patients.² 

          • During life, heart disease using echocardiography has been identified in about 25% of AIDS patients.

        • In the early stages of the HIV epidemic, cardiomyopathy (heart muscle disease) was the major cardiovascular complication of HIV infection.^2,9 

          • Tuberculosis pericarditis, cardiomyopathy, pericardial effusion and pulmonary hypertension both initially and at the present time remain important cardiac diseases in Africa.

            • These presentations relate to the small number of patients (about 5%) who may have access to contemporary antiretroviral agents.

        • One of the major studies concerning the effects of HIV/AIDS on heart disease was conducted in South Africa.¹¹ 

          • The study was known as the Heart of Soweto Study. In this prospective analysis of all de novo heart disease cases presented to the Cardiology Unit during 2006-2008 of the Chris Hani Baragwanath Hospital 5328 de novo heart disease cases were considered.¹¹ 

            • About 10% of these cases (518/5328) represented HIV-positive patients and about half of these patients were given cART (HAART: highly active antiretroviral treatment) upon presentation.

            • The most frequently noted primary diagnosis related to HIV/AIDS was HIV-related cardiomyopathy (38% of the 518 patients).¹¹  

        • At present heart disease in HIV patients is now manifest in developed countries as coronary heart disease.^2,9

          • The rate of myocardial infarction (MIs) is approximately 3.5/1000 patient-years. Furthermore, about 30% of these incidences were fatal.

          • The use of cART (HAART), highly active antiretrovirals, often consisting of two nucleoside reverse transcriptase inhibitors [NRTIs] along with one or two protease inhibitors appears to be the basis of the change in heart disease pattern since the beginning of the epidemic.

            • cART-induced metabolic abnormalities, especially insulin resistance and hyperlipidemia appear important aspects of the problem.⁹

        • Generally, in HIV patients, cardiovascular disease may be accounted for by expected risk factors including smoking, HIV infection-related, or complication of antiretroviral drugs.² 

          • Patients with HIV infection exhibit both lower levels of high-density lipoprotein cholesterol (HDL, "good cholesterol") and higher levels of triglycerides; furthermore a higher incidence of smoking appears to be present in HIV-populations compared to comparable cohorts without HIV infection.

          • The rate of cardiovascular disease has been shown lower to be in patients treated with antiretroviral drugs.

            • This finding identified a relationship between HIV replication and cardiovascular disease risk.² 

              • CD4⁺ T cell counts of <500/μl appears to be an independent risk factor for cardiovascular disease.

                • This risk factor appears comparable to the risk factor smoking.² 

      • Cardiomyopathy

        • Idiopathic Cardiomyopathy, Gross Pathology¹²

          CDC/Ewing Jr EP Gross pathology of idiopathic cardiomyopathy:  gross pathology (1972) "Opened left ventricle of heart shows a thickened, dilated left ventricle with a subendocardial fibrosis manifested as increased whiteness of endocardioumm. Autopsy."

        • HIV-associated cardiomyopathy is characterized as a dilated cardiomyopathy presenting with congestive heart failure (CHF).² 

          •  

            Distribution of HIV-related Primary Cardiovascular Diseases^10,11

            Thienemann F Sliwa K Rockstroh JK HIV and the heart: the impact of antiretroviral therapy: a global perspective. Eur heart J 34(46): 3538-3546 Dec. 2013. http://eurheartj.oxfordjournals.org/content/ehj/early/2013/10/14/eurheartj.eht388.full.pdf Sliwa K Carrington MJ Becker A Thienemann F Ntsekhe M Stewart S Contribution of the human immunodeficieny virus/acquired immunodeficiency syndrome epidemic to de novo presentations of heart disease in the Heart of Soweto Study cohort. Eur heart J 33(7): 866-874, 2012. (second sourced from reference 10). Figure attribution: This figure corresponds to Figure 3 in reference 10 and Figure 1 in reference 11.

          • This cardiomyopathy occurs in the latter stages of HIV infection and histologically resembles myocarditis.

        • Dilated cardiomyopathy associated with HIV infection was initially described in 1986 and exhibits characteristics similar to idiopathic dilated cardiomyopathy in HIV-negative individuals.⁹ 

          • Associated isolated left ventricular dysfunction in HIV-AIDS patients may be due to a self-limiting myocarditis, since the dysfunction may resolve on its own.⁹

            • The differential diagnosis of cardiomyopathy in the HIV/AIDS setting takes into account:⁹

              • Left ventricular dysfunction due to ischemic heart disease

              • Hypertension

              • Diabetes

              • Coronary vasospasm (secondary to cocaine use) as well as

              • Drug hypersensitivity reactions.⁹

            • Heart muscle disease is associated with prevalence of about 4.5% for cardiomyopathy and 6.5% for left ventricular dysfunction.⁹ 

              • These conditions may present as clinical symptoms in about 6% of HIV/AIDS patients.⁹ 

          • Cardiomyopathy has a poor prognosis, suggesting poor survival in these patients when compared to similar patients with structurally normal myocardium.⁹

            • The HIV cardiomyopathy-associated poor prognosis remains poor even after taking into account CD4 levels.

              • The underlying mechanism for cardiomyopathy and left ventricular dysfunction in HIV/AIDS remains incompletely understood.

              • Suggestions of possible mechanisms include:

                • Pathologies due to HIV and HIV-associated proteins

                • Cytokines

                • Lymphocytic myocarditis

                • Autoimmune response abnormalities

                • Drugs,

                • Suboptimal nutrition et al.⁹

        • Other Cardiovascular Dysfunctions Described in HIV Patients²

          • In patients with HIV infection other cardiovascular dysfunctions in addition to those previously described may also be present.²  

            • Advanced HIV disease may cause pericardial effusions.²  

              •  

                Pericardial Effusion with Tamponade

                "A 2D transthoracic Echocardiogram of pericaridal effusion. The Swinging Heart" Attribution:  By Jer5150 (Own work) [GFDL (http://www.gnu.org/copyleft/fdl.html) or CC BY-SA 3.0 (http://creativecommons.org/licenses/by-sa/3.0)], via Wikimedia Commons http://commons.wikimedia.org/wiki/File%3APericardial_effusion_with_tamponade.gif

              •  

                Pericardial Effusion (Chest X-ray):  "Water-bottle Shaped Heart"

                Jer5150 "Water bottle" May 26, 2012 http://commons.wikimedia.org/wiki/File:Water_bottle.png

              • Factors that may increase the likelihood of pericardial effusion include:

                • Tuberculosis

                • Congestive heart failure

                • Cryptococcal or myobacterial infection

                • Pulmonary infection

                • Kaposi's sarcoma

                • Lymphoma.

              • Pericardial Kaposi's sarcoma may be associated with both tamponade and death, probably due to acute hemorrhage.

              • Occasionally, nonbacterial thrombotic endocarditis may occur.

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. Lewis W Currie PF Chapter 93 HIV/AIDS and the Cardiovascular System (in Hurst's The Heart, 13 e Fuster V, Walsh RA Harrington RA, eds; Hunt AS King III SB Nash IS Prystowsky EN Roberts R Rose E, Assoc eds) The McGraw-Hill Companies, Inc 2011. Thienemann F Sliwa K Rockstroh JK HIV and the heart:  the impact of antiretroviral therapy:  a global perspective.  Eur heart J 34(46):  3538-3546 Dec. 2013. http://eurheartj.oxfordjournals.org/content/ehj/early/2013/10/14/eurheartj.eht388.full.pdf Sliwa K Carrington MJ Becker A Thienemann F Ntsekhe M Stewart S Contribution of the human immunodeficieny virus/acquired immunodeficiency syndrome epidemic to de novo presentations of heart disease in the Heart of Soweto Study cohort. Eur heart J 33(7):  866-874, 2012. CDC/Ewing Jr EP Gross pathology of idiopathic cardiomyopathy:  gross pathology (1972) http://commons.wikimedia.org/wiki/File:Idiopathic_cardiomyopathy,_gross_pathology_20G0018_lores.jpg Pearce D, Hicks C et al. HIV Infection and Cardiovascular Health:  ICAAC, Sept.9, 2012, San Francisco, CA (American Society for Microbiology) https://www.youtube.com/watch?v=1PMqkSalZps

 

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