Trizivir (Abacavir/Lamivudine/Zidovudine) plus Lopinavir/Ritonavir Induction Therapy Followed by Trizivir-Alone Maintenance for HIV-1-Infected Patients: A 96-Week Pilot Treatment Simplification Study


Objective: The purpose of this study was to investigate whether switching HIV-infected patients stabilized on Trizivir (abacavir 300 mg/lamivudine 150 mg/zidovudine 300 mg) plus lopinavir/ritonavir 400 mg/100mg twice daily to Trizivir alone affects clinical efficacy and tolerability. Methods: This phase 4, open-label, pilot study was conducted over 96 weeks in 23 antiretroviral-naïve, HIV-infected patients. Initially, these patients received induction therapy with Trizivir plus lopinavir/ritonavir 400 mg/100mg twice daily. Patients who achieved a viral load < 50 copies/mL at week 36 or 44 started maintenance therapy with Trizivir alone at week 48 and continued this regimen through week 96. Results: The study population was a median of 37 years of age, predominantly male (78%) and African American (61%, with 39% Caucasians), and had a baseline mean viral load of 5.45 log10 copies/mL and CD4+ count of 232 cells/mm3. Nineteen patients completed induction; of the four who did not, three were lost to follow-up and one withdrew due to gastrointestinal adverse events. In 14 induction completers who had viral load measurements taken at week 48, intent-to-treat: observed analysis showed a week 48 viral load < 400 copies/mL attained in 100% (14/14) and <50 copies/mL attained in 71% (10/14). Median week 48 CD4+ cell count was 192 cells/mm3 higher than the baseline count. Twelve patients completed the subsequent 48-week Trizivir-alone maintenance phase, of whom 11 (92%) achieved viral loads of both <400 and <50 copies/mL at week 96. Median week 96 CD4+ cell count was 208 cells/mm3 above baseline. Trizivir-only maintenance was associated with fewer adverse events than the Trizivir-lopinavir/ritonavir induction phase and with improvement in total cholesterol, LDL-cholesterol, and triglycerides. Conclusions: Trizivir-alone maintenance after Trizivir-lopinavir/ritonavir induction maintained virologic and CD4+ cell response, and was associated with an improved adverse event and lipid profile.

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J. C. Gathe, D. T. Martin, M. Keith Rawlings, B. Daquioag, J. E. Fuchs, V. C. Williams, K. L. Oie and G. E. Pakes, "Trizivir (Abacavir/Lamivudine/Zidovudine) plus Lopinavir/Ritonavir Induction Therapy Followed by Trizivir-Alone Maintenance for HIV-1-Infected Patients: A 96-Week Pilot Treatment Simplification Study," World Journal of AIDS, Vol. 2 No. 3, 2012, pp. 245-251. doi: 10.4236/wja.2012.23032.

Conflicts of Interest

The authors declare no conflicts of interest.


[1] M. E. Curlin, T. Wilkin and J. Mittler, “Induction-Maintenance Therapy for HIV-1 Infection,” Future of HIV Therapy, Vol. 2, No. 2, 2008, pp. 175-185. doi:10.2217/17469600.2.2.175
[2] M. H. E. Reijers, G. J. Weverling, S. Jurriaans, et al., “Maintenance Therapy after Quadruple Induction Therapy in HIV-1-Infected Individuals: Amsterdam Duration of Antiretroviral Medication (ADAM) Study,” Lancet, Vol. 352, No. 9123, 1998, pp. 185-190. doi:10.1016/S0140-6736(98)06193-5
[3] G. Pialoux, F. Raffi, F. Brun-Vezinet, et al., “A Randomized Trial of Three Maintenance Regimens Given after Three Months of Induction Therapy with Zidovudine, Lamivudine, and Indinavir in Previously Untreated HIV-1-Infected Patients,” New England Journal of Medicine, Vol. 339, No. 18, 1998, pp. 1269-1276. doi:10.1056/NEJM199810293391802
[4] J. R. Arribas, F. Puliod, R. Delgado, et al., “Lopinavir/Ritonavir as Single-Drug Therapy for Maintenance of HIV-1 Viral Suppression: 48-Week Results of a Randomized, Controlled, Open-Label, Proof-of-Concept Pilot Clinical Trial (OK Study),” Journal of Acquired Immune Deficiency Syndrome, Vol. 40, No. 3, 2005, pp. 280-287. doi:10.1097/01.qai.0000180077.59159.f4
[5] R. E. Campo, R. Lalanne, T. J. Tanner, et al., “Lopinavir/Ritonavir Maintenance Monotherapy after Successful Viral Suppression with Standard Highly Active Antiretroviral Therapy in HIV-1-Infected Patients,” AIDS, Vol. 19, No. 4, 2005, pp. 447-449. doi:10.1097/01.aids.0000161777.38438.ed
[6] P. Vernazza, S. Daneel, V. Schiffer, et al., “The Role of Compartment Penetration in PI-Monotherapy: The Atazanavir-Ritonavir Monomaintenance (ATARITMO) Trial,” AIDS, Vol. 21, No. 10, 2007, pp. 1309-1315. doi:10.1097/QAD.0b013e32814e6b1c
[7] J.-F. Delfraissy, P. Flandre, C. Delaugerre, et al., “Lopinavir/Ritonavir Monotherapy or Plus Zidovudine and Lamivudine in Antiretroviral-Naive HIV-Infected Patients,” AIDS, Vol. 22, No. 3, 2008, pp. 385-393. doi:10.1097/QAD.0b013e3282f3f16d
[8] S. Swindells, A. G. DiRienzo, T. Wilkin, et al., “Regimen Simplification to Atazanavir-Ritonavir Alone as Main- tenance Antiretroviral Therapy after Sustained Virologic Suppression,” Journal of the American Medical Association, Vol. 296, No. 7, 2006, pp. 806-814. doi:10.1001/jama.296.7.806
[9] F. Pulido, J. R. Arribas, R. Delgado, et al., “Lopinavir-Ritonavir Monotherapy versus Lopinavir-Ritonavir and Two Nucleosides for Maintenance Therapy of HIV,” AIDS, Vol. 22, No. 2, 2008, pp. F1-F9. doi:10.1097/QAD.0b013e3282f4243b
[10] M. Markowitz, C. Hill-Zabala, J. Lang, et al., “Induction with Abacavir/Lamivudine/Zidovudine Plus Efavirenz for 48 Weeks Followed by 48-Week Maintenance with Abacavir/Lamivudine/Zidovudine Alone in Antiretroviral-Na?ve HIV-1-Infected Patients,” Journal of Acquired Immune Deficiency Syndrome, Vol. 39, No. 3, 2005, pp. 257-264. doi:10.1097/01.qai.0000169664.15536.20
[11] S. De Wit, M. Johnson, B. Gazzard, et al., “Randomised Comparison of Maintenance Therapy with Trizivir [TZV] + Efavirenz [EFV] vs TZV in Naive HIV-1-Infected Subjects: TIME Study,” 7th International Congress on Drug Therapy in HIV Infection, Glasgow, 14-18 Novem- ber 2004, Abstract PL2.4.
[12] P. Keiser and N. Nassar, “Abacavir Sulfate/Lamivudine/Zidovudine Fixed Combination in the Treatment of HIV Infection,” Expert Opinion in Pharmacotherapy, Vol. 8, No. 4, 2007, pp. 477-483. doi:10.1517/14656566.8.4.477
[13] Panel on Antiretroviral Guidelines for Adults and Adolescents, “Guidelines for the Use of Antiretroviral Agents in HIV-1-Infected Adults and Adolescents,” Department of Health and Human Services, 2012, pp. 1-239.
[14] M. A. Thompson, J. A. Aberg, P. Cahn, et al., “Antiretroviral Treatment of Adult HIV Infection 2010 Recommendations of the International AIDS Society, USA Panel,” Journal of the American Medical Association, Vol. 304, No. 3, 2010, pp. 321-333. doi:10.1001/jama.2010.1004
[15] R. van Raalte, B. Heere, R. Regez, et al., “Induction- Maintenance Strategy Re-Evaluated: Initial Boosted-PI in Combination with Triple NRTI, Followed by Triple NRTI Maintenance,” 15th International AIDS Conference, 11-16 July 2004, Bangkok, Abstract TuPeB4597.
[16] J. Mallolas, J. Pich, M. Pe?aranda, et al., “Induction Therapy with Trizivir Plus Efavirenz or Lopinavir/Ritonavir Followed by Trizivir Alone in Na?ve HIV-1-Infected Adults,” AIDS, Vol. 22, No. 3, 2008, pp 377- 384. doi:10.1097/QAD.0b013e3282f3db2c
[17] J. Reynes, J. M. Ragnaud, B. Delmas, et al., “An Open-Label Study to Evaluate Long-Term (96 Weeks) Safety and Efficacy of Switch to Trizivir After First Line Quadruple Induction Therapy: AZLF3004, Trisud,” 9th European AIDS Conference (EACS), Warsaw, 25-29 October 2003, Poster 7.5/3.
[18] National Institute of Allergy and Infectious Diseases (NIAID), “Table for Grading the Severity of Adult and Pediatric Adverse Events, Version 1.0,” Division of Acquired Immunodeficiency Syndrome (DAIDS), Washington DC, 2004.
[19] 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.
[20] M. Duong, L. Piroth, M. Grappin, et al., “Evaluation of the Patient Medication Adherence Questionnaire as a Tool for Self-Reported Adherence Assessment in HIV- Infected Patients on Antiretroviral Regimens,” HIV Clinical Trials, Vol. 2, No. 2, 2001, pp. 128-135. doi:10.1310/M3JR-G390-LXCM-F62G
[21] A. S. Perelson, P. Essunger, Y. Cao, et al., “Decay Characteristics of HIV-1-Infected Compartments during Combination Therapy,” Nature, Vol. 387, No. 6629, 1997, pp. 188-191. doi:10.1038/387188a0
[22] E. Martínez, J. A. Arnaiz, D. Podzamczer, et al., “Substitution of Nevirapine, Efavirenz, or Abacavir for Protease Inhibitors in Patients with Human Immuno-deficiency Virus Infection,” New England Journal of Medicine, Vol. 349, No. 11, 2003, pp. 1036-1046. doi:10.1056/NEJMoa021589
[23] C. Katlama, S. Fenske, B. Gazzard, et al., “TRIZAL Study: Switching from Successful HAART to Trizivir? (Abacavir-Lamivudine-Zidovudine Combination Tablet): 48 Weeks Efficacy, Safety and Adherence Results,” HIV Medicine, Vol. 4, No. 2, 2002, pp. 79-86. doi:10.1046/j.1468-1293.2003.00139.x
[24] M. Opravil, B. Hirschel, A. Lazzarin, et al., “A Randomized Trial of Simplified Maintenance Therapy with Abacavir, Lamivudine, and Zidovudine in Human Immunodeficiency Virus Infection,” Journal of Infectious Diseases, Vol. 185, No. 9, 2005, pp. 1251-1260. doi:10.1086/340312
[25] N. Clumeck, F. Goebel, W. Rozenbaum, et al., “Simplification with Abacavir-Based Triple Nucleoside Therapy versus Continued Protease Inhibitor-Based Highly Active Antiretroviral Therapy in HIV-1-Infected Patients with Undetectable Plasma HIV-1 RNA,” AIDS, Vol. 15, No. 12, 2001, pp. 1517-1526. doi:10.1097/00002030-200108170-00009
[26] H. G. Sprenger, N. Langebeek, P. G. H. Mulder, et al., “Abacavir/Lamivudine/Zidovudine Maintenance after Standard Induction in Antiretroviral Therapy-Na?ve Patients: FREE Randomized Trial Interim Results,” AIDS Patient Care and STDs, Vol. 24, No. 6, 2010, pp. 361-366. doi:10.1089/apc.2009.0236
[27] 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
[28] C. Hicks, M. Fischl, S. Greenberg, et al., “Ziagen? (Abacavir, ABC, 1592) Combined with 3TC and ZDV Provides a Potent and Durable Response Through 48 Weeks in HIV-1-Infected Antiretroviral Therapy (ART)-Na?ve Adults (CNA3003),” 37th Annual Meeting of the Infectious Disease Society of America, Philadelphia, 18- 20 November 1999, Abstract/Poster 341.
[29] P. de Truchis, D. Mathez, G. Force, et al., “Long-Term Control of Viral Residual Replication under Maintenance Therapy with Trizivir after a Quadruple Induction Regimen in HIV-1-Infected Adults (Suburbs Trial),” HIV Clinical Trials, Vol. 8, No. 2, 2007, pp. 102-104. doi:10.1310/hct0802-102

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