Virologic and Lipoprotein Changes after Halving Ritonavir Boosting in HIV-Infected Patients Stabilized on Once-Daily Fosamprenavir plus Abacavir/Lamivudine


Background: The effect of reducing ritonavir boosting doses on the efficacy and safety of fosamprenavir-based regimens has not been well studied. Methods: In a 52-week, phase 4, open-label, single-center pilot study, 26 antiretroviral-naive, HIV-infected patients with viral loads >1000 copies/mL received induction with fosamprenavir/ritonavir 1400 mg/200mg plus abacavir/lamivudine 600 mg/300mg once daily for 28 weeks. Patients achieving a viral load <50 copies/mL at week 28 were given maintenance therapy for 24 subsequent weeks with half the ritonavir dose (100 mg) plus the usual fosamprenavir, lamivudine, and abacavir doses. Results: The study population (n = 26) was diverse regarding sex (14 females/12 males) and race (16 black, 10 white). Baseline median viral load was 4.93 log10 copies/mL and CD4+ count 110/mm3. Of 12 induction/maintenance completers, 10 (83%) achieved viral loads <50 copies/mL by maintenance-week 24. Median CD4+ count increased from 110/mm3 at baseline to 292/mm3 at induction-week 28 and to 296/mm3 at maintenance-week 24. The incidence of adverse events at maintenance-week 24 did not differ from that at induction-week 28 (P > 0.05). Median fasting total-cholesterol, LDL-cholesterol, and triglycerides remained below NCEP cut-off levels. Baseline/induction-week 28/maintenance-week 24 median total-cholesterol was 130/177/183 mg/dL, LDL-cholesterol 78/107/114 mg/dL, HDL-cholesterol 33/41/43 mg/dL, total-cholesterol: HDL-cholesterol ratio 3.9/4.3/4.3, and triglycerides 93/145/119 mg/dL. During induction, total VLDL/chylomicron, LDL, and HDL particles increased; during maintenance, VLDL/chylomicron particles decreased, but LDL and HDL particle concentrations did not notably change. Conclusions: Reducing ritonavir boosting from 200 mg to 100 mg once daily in HIV-infected patients stabilized on once-daily fosamprenavir/abacavir/lamivudine resulted in maintenance of virologic suppression, enhanced CD4+ count, and improved triglycerides.

Share and Cite:

D. T. Jayaweera and G. E. Pakes, "Virologic and Lipoprotein Changes after Halving Ritonavir Boosting in HIV-Infected Patients Stabilized on Once-Daily Fosamprenavir plus Abacavir/Lamivudine," World Journal of AIDS, Vol. 2 No. 2, 2012, pp. 109-116. doi: 10.4236/wja.2012.22015.

Conflicts of Interest

The authors declare no conflicts of interest.


[1] H. A. Torres and R. C. Arduino, “Fosamprenavir Calcium Plus Ritonavir for HIV Infection,” Expert Review of Anti- Infective Therapy, Vol. 5, No. 3, 2007, pp. 349-363. doi:10.1586/14787210.5.3.349
[2] A. Hill, J. Van Der Lugt, W. Sawyer and M. Boffito, “How Much Ritonavir Is Needed to Boost Protease Inhibitors? Systematic Review of 17 Dose-ranging Pharmacokinetic Trials,” AIDS, Vol. 23, No. 17, 2009, pp. 2237-2245. doi:10.1097/QAD.0b013e328332c3a5
[3] J. C. Gathe Jr., P. Ive, R. Wood, D. Schürmann, N. C. Bellos, E. DeJesus, et al., “SOLO: 48-Week Efficacy and Safety Comparison of Once-Daily Fosamprenavir/Ritonavir Versus Twice-Daily Nelfinavir in Naive HIV-1-Infected Patients,” AIDS, Vol. 18, No. 11, 2004, pp. 1529-1537. doi:10.1097/01.aids.0000131332.30548.92
[4] S. A. Danner, A. Carr, J. M. Leonard, L. M. Lehman, F. Gudiol, J. Gonzales, et al., “A Short-Term Study of the Safety, Pharmacokinetics, and Efficacy of Ritonavir, an Inhibitor of HIV-1 Protease,” New England Journal of Medicine, Vol. 333, No. 23, 1995, pp. 1528-1533. doi:10.1056/NEJM199512073332303
[5] G. Gatti, A. Di Biagio, R. Casazza, C. De Pascalis, M. Bassetti, M. Cruciani, et al., “The Relationship between Ritonavir Plasma Levels and Side-Effects: Implications for Therapeutic Drug Monitoring,” AIDS, Vol. 13, No. 15, 1999, pp. 2083-2089. doi:10.1097/00002030-199910220-00011
[6] M. Sension and P. J. Piliero. “Ritonavir-Boosted Protease Inhibitors: Impact of Ritonavir on Toxicities in Treatment-Experienced Patients,” Journal of the Association of Nurses in AIDS Care, Vol. 18, No. 1, 2007, pp. 36-47. doi:10.1016/j.jana.2006.11.003
[7] G. Carosi, A. Lazzarin, H. Stellbrink, G. Moyle, S. Rugina, S. Staszewski, et al., “Study of Once-Daily Versus Twice-Daily Fosamprenavir Plus Ritonavir Administered with Abacavir/Lamivudine Once Daily in Antiretroviral-Na?ve HIV-1-Infected Adult Subjects,” HIV Clinical Trials, Vol. 10, No. 6, 2009, pp. 356-367. doi:10.1310/hct1006-356
[8] C. B. Hicks, E. DeJesus, L. M. Sloan, M. G. Sension, D. A. Wohl, Q. Liao, 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, 209, pp. 395-403.
[9] S. De Wit, B. Poll, C. Necsoi and N. Clumeck, “Fosamprenavir Boosted with a Single 100 mg Capsule of Ritonavir as Part of a Once Daily First Line Regimen in Na?ve Patients,” 8th International Congress on Drug Therapy in HIV Infection, Glasgow, 12-16 November 2006, p. 17.
[10] P. Muret, D. Montange, D. Bettinger, J. Faller, B. Martha and G. Beck-Wirth, “Assessment of Amprenavir Plasma Cmin Levels in Patients Receiving Once-Daily Fos-Amprenavir in Combination with Either 100 or 200 mg Ritonavir,” 8th International Workshop on Clinical Pharmacology of HIV Therapy, Budapest, 16-18 April 2007, p. 26.
[11] K. Y. Smith, W. G. Weinberg, E. De Jesus, M. A. Fischl, Q. Liao, L. L. Ross, et al., “Fosamprenavir or Atazanavir Once Daily Boosted with Ritonavir 100 mg, Plus Te- nofovir/Emtricitabine, for the Initial Treatment of HIV Infection: 48-Week Results of ALERT,” AIDS Research and Therapy, Vol. 5, No. 5, 2008, pp. 1-10.
[12] G. Blick, P. Greiger-Zanlungo, V. Plasencia, S. Gretz, J. Han, D. DuPree, et al., “Long-Term Efficacy and Safety of Fosamprenavir (FPV) 1400 mg Once Daily (QD) Boosted by Ritonavir (r) 100 mg QD in Antiretroviral-Naive HIV+ Patients and in Antiretroviral-Experienced Patients Switched to FPV/r Due to Intolerance to Prior Regimens: BOLD100 (COL109766),” Annual Meeting of the American College of Clinical Pharmacy, Denver, 14-17 October 2007, p. 110E.
[13] R. Hsu, K. Walker-Reed and E. Acosta, “Fosamprenavir (FPV) with Low-Dose Ritonavir (RTV) Once Daily (QD) in HIV-Infected Subjects,” 7th International Workshop on Clinical Pharmacology of HIV Therapy, Lisbon, 20-22 April 2006, p. 71.
[14] E. Latuada, M. Lanzafame, C. Grosso, F. Soldani, F. Corsini, S. Storato, et al., “Optimal Fosamprenavir Regimen to Prevent Lipid Abnormalities,” Acta Bio-Medica, Vol. 80, No. 3, 2009, pp. 200-202.
[15] C. Cohen, E. DeJesus, A. La Marca, B. Young, L. Yau, L. Patel, 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
[16] D. A. Parks, H. C. Jennings, C. Taylor, G. E. Pakes and E. P. Acosta, “Steady-State Amprenavir, Tenofovir, Emtricitabine, and Ritonavir 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
[17] P. J. Ruane, A. D. Luber, M. B. Wire, Y. Lou, M. J. Shelton, C. T. Lancaster, et al., “Plasma Amprenavir Pharmacokinetics and Tolerability Following Administration of 1,400 Milligrams of Fosamprenavir Once Daily in Combination with Either 100 or 200 Milligrams of Ritonavir in Healthy Volunteers,” Antimicrobial Agents and Chemotherapy, Vol. 51, No. 2, 2007, pp. 560-565. doi:10.1128/AAC.00560-06
[18] M. Sale, B. M. Sadler and D. S. Stein, “Pharmacokinetic Modeling and Simulations of Interaction of Amprenavir and Ritonavir,” Antimicrobial Agents and Chemotherapy, Vol. 46, No. 3, 2002, pp. 746-754. doi:10.1128/AAC.46.3.746-754.2002
[19] R. Wood, K. Arasteh, H-J. Stellbrink, E. Teofilo, F. Raffi, R. B. Pollard, et al., “Six-Week Randomized Controlled Trial to Compare the Tolerabilities, Pharmacokinetics, and Antiviral Activities of GW433908 and Amprenavir in Human Immunodeficiency Virus Type 1-Infected Patients,” Antimicrobial Agents and Chemotherapy, Vol. 48, No. 1, 2004, pp. 116-123. doi:10.1128/AAC.48.1.116-123.2004
[20] Food and Drug Administration, “FDA Approves Administration of LEXIVA with Lower Dose of ‘Boosting’ Medication Ritonavir,” GlaxoSmithKline, Inc., Mississauga, 2007.
[21] National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III), “Third Report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III): Final Report,” Circulation, Vol. 106, No. 25, 2002, pp. 3143-3421.
[22] T. Hawkins, “Understanding and Managing the Adverse Effects of Antiretroviral Therapy,” Antiviral Research, Vol. 85, No. 1, 2010, pp. 201-209. doi:10.1016/j.antiviral.2009.10.016
[23] J. D. Brunzell, M. Davidson, C. D. Furberg, R. B. Goldberg, B. V. Howard, J. H. Stein, et al., “Lipoprotein Management in Patients with Cardiometabolic Risk: Consensus Conference Report from the American Diabetes Association and the American College of Cardiology Foundation,” Journal of the American College of Cardiology, Vol. 51, No. 15, 2008, pp. 1512-1524. doi:10.1016/j.jacc.2008.02.034
[24] S. Collot-Teixetra, F. De Lorenzo, L. Waters, C. Fletcher, D. Back, S. Mandalia, et al., “Impact of Different Low-Dose Ritonavir Regimens on Lipids, CD36, and Adipophilin Expression,” Clinical Pharmacology and Therapeutics, Vol. 85, No. 4, 2009, pp. 375-378. doi:10.1038/clpt.2008.243
[25] A. Mathias, S. West, J. Hui and B. P. Kearney, “Dose-Response of Ritonavir on Hepatic CYP3A Activity and Elvitegravir Oral Exposure,” Clinical Pharmacology and Therapeutics, Vol. 85, No. 1, 2009, pp. 64-70. doi:10.1038/clpt.2008.168
[26] I. V. Bassett, C. Farel, E. D. Szmuilowicz and R. P. Walensky, “AIDS Drug Assistance Programs in the Era of Routine HIV Testing,” Clinical Infectious Diseases, Vol. 47, No. 5, 2008, pp. 695-701. doi:10.1086/590936

Copyright © 2023 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.