Share This Article:

Impact of Switch to Fosamprenavir and Addition of Lovaza® for Treatment of Hypertriglyceridemia in HIV-Infected Subjects on Antiretroviral Therapy

Abstract Full-Text HTML Download Download as PDF (Size:300KB) PP. 24-32
DOI: 10.4236/wja.2012.21004    2,712 Downloads   4,952 Views  

ABSTRACT

Background: Managing hypertriglyceridemia in HIV-infected patients often requires multiple pharmacologic strategies. Many protease inhibitors (PIs), one of 6 classes of drugs used to treat HIV, have been associated with hypercholesterolemia and drug interactions. For this study, we examined a dual strategy to manage hypertriglyceridemia in HIV-infected patient taking PIs: 1) switching patients to fosamprenavir (FPV), a PI with fewer drug interactions, and 2) adding prescription fish oil (LOVAZA?), which has been shown to reduce triglycerides. Methods: This multicenter, 24-week study enrolled 36 patients virologically suppressed (HIV-1 RNA <50 copies/mL) on PI-containing therapy with screening triglyceride levels of 200 - 1200 mg/dL and LDL cholesterol levels ≤160 mg/dL. At baseline, patients were switched to ritonavir (RTV)-boosted fosamprenavir (FPV 1400 mg/RTV 100 mg QD) and any lipid-lowering agents were stopped. At Week 6, LOVAZA 4 g QD was added. Results: Five patients prematurely discontinued due to adverse events (2), non-compliance, lost-to-follow up, and protocol violation. Median triglyceride concentration was 303 mg/dL at screening, 262 mg/dL at baseline, 290 mg/dL at Week 6 (+8% from baseline), and 218 mg/dL at Week 24 (–30% from Week 6). At Week 24, 39% (12/31) of patients had triglycerides <200 mg/dL. Among patients reaching Week 24, 100% (31/31) and 90% (28/31) had HIV-1 RNA <400 and <50 copies/mL, respectively. Conclusions: In this study, a switch to FPV/RTV followed by LOVAZA decreased median triglyceride levels and modestly increased the percentage of patients with triglyceride levels <200 mg/dL while maintaining virologic suppression in HIV-infected subjects with hypertriglyceridemia. Our data suggest that baseline PI may affect the likelihood of achieving triglycerides <200 mg/dL after 18 weeks on study. A larger study would be needed to understand the relative contributions of choice of protease inhibitor and LOVAZA to triglyceride concentrations in HIV-infected patients.

Conflicts of Interest

The authors declare no conflicts of interest.

Cite this paper

F. Felizarta, A. Scarsella, H. Khanlou, W. Young, L. Ross, H. Zhao, K. Pappa and B. Ha, "Impact of Switch to Fosamprenavir and Addition of Lovaza® for Treatment of Hypertriglyceridemia in HIV-Infected Subjects on Antiretroviral Therapy," World Journal of AIDS, Vol. 2 No. 1, 2012, pp. 24-32. doi: 10.4236/wja.2012.21004.

References

[1] DHHS Panel on Antiretroviral Guidelines for Adults and Adolescents, “Guidelines for the Use of Antiretroviral Agents in HIV-1-Infected Adults and Adolescents,” 10 January 2011. http://aidsinfo.nih.gov/contentfiles/AdultandAdolescentGL.pdf
[2] National Cholesterol Education Program (NCEP), “Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III), Final Report,” National Institutes of Health Publication, No. 02-5215, 2002.
[3] M. P. Dube, J. H. Stein, J. A. Aberg, et al., “Guidelines for the Evaluation and Management of Dyslipidemia in Human Immunodeficiency Virus (HIV)-Infected Adults Receiving Antiretroviral Therapy: Recommendations of the HIV Medicine Association of the Infectious Disease Society of America and the Adult AIDS Clinical Trials Group,” Clinical Infectious Diseases, Vol. 37, No. 5, 2003, pp. 613-627. doi:10.1086/378131
[4] D. A. Wohl, H. C. Tien, M. Busby, et al., “Randomized Study of the Safety and Efficacy of Fish Oil (Omega-3 Fatty Acid) Supplementation with Dietary and Exercise Counseling for the Treatment of Antiretroviral Therapy-Associated Hypertriglyceridemia,” Clinical Infectious Diseases, Vol. 41, No. 10, 2005, pp. 1495-1504.
[5] J. H. Stein, Y. Wu, H. Kawabata and U. H. Iloeje, “Increased Use of Lipid-Lowering Therapy in Patients Receiving Human Immunodeficiency Virus Protease Inhibitors,” American Journal of Cardiology, Vol. 92, No. 3, 2003, pp. 270-274. doi:10.1016/S0002-9149(03)00622-2
[6] M. Schambelan, C. A. Benson, A. Carr, et al., “Management of Metabolic Complications Associated with Antiretroviral Therapy for Hiv-1 Infection: Recommendations of an International AIDS Society—USA Panel,” Journal of Acquired Immune Deficiency Syndromes, Vol. 31, No. 3, 2002, pp. 257-275.
[7] L. Calza, R. Manfredi and F. Chiodo, “Use of Fibrates in the Management of Hyperlipidemia in HIV-Infected Patients Receiving HAART,” Infection, Vol. 30, No. 1, 2002, pp. 26-31.
[8] A. Rao, S. D’Amico, A. Balasubramanyam and M. Maldonado, “Fenofibrate Is Effective in Treating Hypertriglyceridemia Associated with HIV Lipodystrophy,” American Journal of the Medical Sciences, Vol. 337, No. 6, 2004, pp. 315-318. doi:10.1097/00000441-200406000-00003
[9] J. A. Aberg, R. A. Zackin, S. W. Brobst, et al., “A Randomized Trial of the Efficacy and Safety of Fenofibrate Versus Pravastatin in HIV-Infected Subjects with Lipid Abnormalities: AIDS Clinical Trials Group Study 5087,” AIDS Research and Human Retroviruses, Vol. 21, No. 9, 2005, pp. 757-767. doi:10.1089/aid.2005.21.757
[10] M. P. Dube, J. W. Wu, J. A. Aberg, et al., “Safety and Efficacy of Extended-Release Niacin for the Treatment of Dyslipidemia in Patients with Human Immunodeficiency Virus Infection: AIDS Clinical Trials Group Study A5148,” Antiviral Therapy, Vol. 11, No. 8, 2006, pp. 1081-1089.
[11] J. M. McKenney and D. Sica, “Role of Prescription Omega-3 Fatty Acids in the Treatment of Hypertriglyceridemia,” Pharmacotherapy, Vol. 27, No. 5, 2007, pp. 715-728. doi:10.1592/phco.27.5.715
[12] W. S. Harris, M. Miller, A. P. Tighe, M. H. Davidson and E. J. Schaefer, “Omega-3 Fatty Acids and Coronary Heart Disease Risk: Clinical and Mechanistic Perspectives,” Atherosclerosis, Vol. 197, No. 1, 2008, pp. 12-24. doi:10.1016/j.atherosclerosis.2007.11.008
[13] B. E. Phillipson, D. W. Rothrock, W. E. Connor, W. S. Harris and D. R. Illingworth, “Reduction of Plasma Lipids, Lipoprotein, and Apoproteins by Dietary Fish Oils in Patients with Hypertriglyceridemia,” New England Journal of Medicine, Vol. 312, No. 19, 1985, pp. 1210-1216. doi:10.1056/NEJM198505093121902
[14] E. B. Schmidt and J. Dyerberg, “Omega-3 Fatty Acids. Current Status in Cardiovascular Medicine,” Drugs, Vol. 47, No. 3, 1994, pp. 405-424. doi:10.2165/00003495-199447030-00003
[15] W. S. Harris, “Nonpharmacologic Treatment of Hypertriglyceridemia: Focus on Fish Oils,” Clinical Cardiology, Vol. 22, No. 6 (Supplement), 1999, pp. 40-43.
[16] LOVAZA Prescribing Information (Omega-3-Acid Ethyl Esters), GlaxoSmithKline, Research Triangle Park, North Carolina, 2008.
[17] C. Cohen, E. DeJesus, A. LaMarca, et al., “Similar Virologic and Immunologic Efficacy with Fosamprenavir Boosted with 100 mg or 200 mg of Ritonavir in HIV-Infected Patients: Results of the LESS Trial,” HIV Clinical Trials, Vol. 11, No. 5, 2010, pp. 239-247. doi:10.1310/hct1105-239
[18] D. A. Parks, H. C. Jennings, C. Taylor, G. E. Pakes and E. P. Acosta, “Steady-State Amprenavir, Tenofovir, and Emtricitabine Pharmacokinetics before and after Reducing Ritonavir Boosting of a Fosamprenavir/Tenofovir/Emtricitabine Regimen from 200 mg to 100 mg Once Daily (TELEX II),” HIV Clinical Trials, Vol. 10, No. 3, 2009, pp. 160-167. doi:10.1310/hct1003-160
[19] C. B. Hicks, E. DeJesus, L. M. Sloan, et al., “Comparison of Once-Daily Fosamprenavir Boosted with either 100 or 200 mg of Ritonavir, in Combination with Abacavir/ Lamivudine: 96-Week Results from COL100758,” AIDS Research and Human Retroviruses, Vol. 25, No. 4, 2009, pp. 395-403. doi:10.1089/aid.2008.0231
[20] L. D. Brown, T. T. Cai and A. DasGupta, “Confidence Intervals for a Binomial Proportion and Asymptotic Expansions,” The Annals of Statistics, Vol. 30, No. 1, 2002, pp. 160-201.
[21] P. De Truchis, M. Kirstetter, A. Perier, et al., “Reduction in Triglyceride Level with N-3 Polyunsaturated Fatty Acids in HIV-Infected Patients Taking Potent Antiretroviral Therapy: A Randomized Prospective Study,” Journal of Acquired Immune Deficiency Syndromes, Vol. 44, No. 3, 2007, pp. 278-285. doi:10.1097/QAI.0b013e31802c2f3d
[22] J. G. Gerber, D. W. Kitch, C. J. Fichtenbaum, et al., “Fish Oil and Fenofibrate for the Treatment of Hypertriglyceridemia in HIV-Infected Subjects on Antiretroviral Therapy: Results of ACTG A5186,” Journal of Acquired Immune Deficiency Syndromes, Vol. 47, No. 4, 2008, pp. 459-466. doi:10.1097/QAI.0b013e31815bace2
[23] H. Bays, “Clinical Overview of Omacor: A Concentrated Formulation of Omega-3 Polyunsaturated Fatty Acids,” American Journal of Cardiology, Vol. 98, No. 4A, 2006, pp. 71i-76i. doi:10.1016/j.amjcard.2005.12.029
[24] D. Skiest, C. Cohen, H. Khanlou, et al., “Randomized Comparison of Darunavir/r Versus Atazanavir/r on Serum Lipids in HIV-Infected Persons on Fully suppressive lopinavir/r or fosamprenavir/r with high Serum Triglycerides. Lopinavir/r or Fosamprenavir/r Switch to Atazanavir/r or Darunavir/r (LARD),” Proceedings of the 18th Conference on Retroviruses and Opportunistic Infections, Boston, 27 February-2 March 2011, poster 817.
[25] E. A. Stein and G. L. Myers for the National Cholesterol Education Program Working Group on Lipoprotein Measurement, “National Cholesterol Education Program Recommendations for Triglyceride Measurement: Executive Summary,” Clinical Chemistry, Vol. 41, No. 10, 1995, pp. 1421-1426.

  
comments powered by Disqus

Copyright © 2018 by authors and Scientific Research Publishing Inc.

Creative Commons License

This work and the related PDF file are licensed under a Creative Commons Attribution 4.0 International License.