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

        • "Cardiovascular Risk Evaluation and Antiretroviral Therapy Effects in an HIV Cohort"⁷

          Attribution: Peters B Cardiovascular risk evaluation and antiretroviral therapy effects in an HIV Cohort. https://www.youtube.com/watch?v=eXsQHxGxGYY (7/210) International Journal of Clinical Practice YouTube Channel:  https://www.youtube.com/channel/UCTEufy2sYxPXLEQfOJumGEQ Aboud M Elgalib A Pomeroy L Panayiotakopoulos G Skopelitis E Kulasegaram R Dimian C Lampe FC Duncan A Wierzbicki AS Peters BS Cardiovascular risk evaluation and antiretroviral therapy effects in an HIV Cohort:  implications for clinical management:  the CREATE 1 study.  International Journal of Clinical Practice:  64(9) 1252-1259, August, 2010. http://onlinelibrary.wiley.com/doi/10.1111/j.1742-1241.2010.02424.x/full

        • Drug-Induced Myocardial Disease (continued)

          • Nucleoside and Nucleotide Reverse Transcriptase Inhibitors⁵

            • Abacavir (Ziagen): Total Cholesterol ↑ ; LDL cholesterol ↑; No effect on glucose; possibly associated with an increased heart attack risk with recent exposure.

            • Azidothymidine (AZT, Zidovudine): Total Cholesterol ↑ ; LDL cholesterol ↑; Insulin Resistance +:  Not associated with increased myocardial infarction risk.

            • Emtricitabine (Emtriva; Coviracil):  No effect on lipids; No effect on glucose; Not associated with increased myocardial infarction risk.

            • Lamivudine (Epivir; Epivir-HBV;3TC);  No effect on lipids; No effect on glucose; Not associated with increased myocardial infarction risk.

            • Stavudine (d4T; Zerit): Total Cholesterol ↑ ; LDL cholesterol ↑; Triglycerides ↑ ; HDL Cholesterol ↓ (dyslipidemia^* +); Not associated with increased myocardial infarction risk.

            • Tenofovir (Viread; TDF):  Total Cholesterol ↓ ; LDL cholesterol ↓; No effect on glucose; Not associated with increased myocardial infarction risk.⁵

          • Non-nucleoside Reverse Transcriptase Inhibitors⁵

            • Efavrirenz (EFV; Sustiva, Stocrin, Efavir and others): Total Cholesterol ↑ ; LDL cholesterol ↑; No effect on glucose; Not associated with increased myocardial infarction risk.

            • Etravirine (ETR, Intelence (TMC125): No effect on lipids; No data on possible drug effects on coronary heart disease.

            • Nevirapine (NVP; Viramune):  HDL Cholesterol ↑; Not associated with increased myocardial infarction risk.

            • Rilpivirine (TNC278; Edurant): No effects on lipids; No data on possible drug effects on coronary heart disease.⁵

          • Protease Inhibitors⁵

            • Amprenavir (Agenerase) + Ritonavir (Norvir):  Dyslipidemia++; Insulin resistance +; Cumulative exposure to this combination constitutes an independent risk factor for myocardial infarction.

            • Atazanavir (Reyataz) + Ritonavir (Norvir):  Dyslipidemia++; Insulin resistance +; Not associated with increased myocardial infarction risk.

            • Darunavir (Prezista) + Ritonavir (Norvir):  Dyslipidemia++; Insulin resistance +; No data on possible drug effects on coronary heart disease.

            • Indinavir (Crixivan):  Dyslipidemia+; Insulin resistance +++;  Unclear association with myocardial infarction risk.

            • Lopinavir + Ritonavir (Combination agent:  Kaletra and Aluvia; Lopinavir not available as a single agent):  Dyslipidemia+++;  Insulin resistance +++; Cumulative exposure to this combination constitutes an independent risk factor for myocardial infarction.

            • Nelfinavir (Viracept):  Dyslipidemia+; Insulin resistance +; Not associated with increased myocardial infarction risk.

            • Saquinavir (Invirase):  Dyslipidemia+; Insulin resistance +; Not associated with increased myocardial infarction risk.

            • Tipranavir (Aptivus) + Ritonavir (Norvir): Dyslipidemia+; Insulin resistance +; No data on possible drug effects on coronary heart disease, i.e. insufficient patients exposed (2013).⁵

          • Integrase Inhibitors⁵

            • Elivitegravir (EVG) /cobicistat (an inhibior of elviegravir metabolism by liver and gut wall cytochrome P450 enzyme isoforms, e.g. CYP3A4); Raltegravir (Isentress): No effect on lipid profile or glucose and No data on possible drug effects on coronary heart disease, i.e. insufficient patients exposed (2013).⁵

          • Entry Inhibitors⁵

            • Maraviroc (Selzentry, Celsentri): No effect on lipid profile or glucose and No data on possible drug effects on coronary heart disease, i.e. insufficient patients exposed (2013).⁵

            *:  Dyslipidemia describes an increase in total cholesterol, an increase in LSL cholesterol, and increase in triglycerides and a decrease in HDL cholesterol; the magnitude of effect is qualitative described as follows:  +, weak effect; ++, moderate effect and +++, important effect.⁵

        • HIV-Associated Electrocardiographic Abnormalities⁵

          • About 50% of HIV patients exhibit abnormal electrocardiograms.^5,8 

            • This prevalence was established in a clinical trial from the Strategies for Management of Antiretroviral Therapy study.⁸ 

              • In that study the clinical trial focused on comparing two HIV treatment approaches.

              • Additionally, electrocardiographic (ECG) abnormalities were classified using the "Minnesota Code".

              • About 51.5% of patients exhibited either minor or major ECG abnormalities with the minor abnormalities being about seven times more frequently found compared to major anomalies.

              • Specific ECG abnormalities predictive of cardiovascular disease involved:⁸ 

                • Major isolated ST-T abnormalities

                • Major QT interval prolongation

                • Minor isolated ST-T and

                • Minor isolated Q-QS abnormalities⁸  .

              • Other examples of major abnormalities involved:⁸ 

                • Ventricular conduction defects

                • Left ventricular hypertrophy

                • Atrial fibrillation/flutter

                • Major AV conduction anomalies

                • Major QT prolongation index (QTI>116%)

                • Major Q-QS wave abnormalities

                • Minor Q-QS with ST-T abnormalities⁸ 

          • QT prolongation which has been observed in HIV can be associated with sudden death.⁵ 

            • Prolongation of the QT ECG interval has also been associated with the HIV treatment of ritonavir-boosted protease inhibitors.⁵  

            • Furthermore, boosted saquinavir prolongs the QT interval to a greater extent than other boosted protease inhibitors, suggesting cautious use. ⁵ 

            • In one clinical study, 100 consecutive AIDS patients were recruited.⁹ 

              • In this study, Nigerian HIV-positive asymptomatic individuals exhibited increased likelihood of QT prolongation compared to HIV-negative subjects.

                • Prevalence of QT prolongation tended to increase as HIV patients were re-classified as having AIDS, upon meeting AIDS-defining criteria.⁹

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. 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://www.ncbi.nlm.nih.gov/pubmed/24126882 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. Peters B Cardiovascular risk evaluation and antiretroviral therapy effects in an HIV Cohort https://www.youtube.com/watch?v=eXsQHxGxGYY Soliman EZ Prineas RJ Roediger MP Duprez DA BGoccara F Boesecke C Stephan C Hodder S Steins JH Lundgred JD Neaton JD Prevalence and progostic significance of ECG abnormalities in HIV-infected patients:  results from the Strategies for Management of Antiretroviral Therapy study.  Journal of Electrocardiology 44:  779-785, 2011. http://www.ncbi.nlm.nih.gov/pubmed/21145066 Sani MU Okeahialam BN QTc Interval Prolongation in Patients with HIV and AIDS.  Journal of the National Medical Association 97(12): 1657-1661.  December 2005.

 

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