A pilot study of switch to lopinavir/ritonavir (LPV/r) monotherapy from nonnucleoside reverse transcriptase inhibitor-based therapy

HIV Clinical Trials

Volumn 7, Issue 5, 2006, Pages 237-245

  Pierone Jr , Gerald ^a,b   Mieras, Jeffrey ^b   Bulgin Coleman, Dorothy ^a   Kantor, Chandra ^a   Shearer, James ^a   Fontaine, Lunie ^c   Fath, Michael ^c   Norton, Michael ^c  

^a AIDS Research and Treatment Center of the Treasure Coast   (United States)

^b Treasure Coast Infectious Disease Consultants   (United States)

^c ABBOTT LABORATORIES   (United States)

Author keywords

HAART; Highly active antiretroviral therapy; Iopinavir ritonavir; LPV r; NNRTIs; Nonnucleoside reverse transcriptase inhibitors; NRTIs; Nucleoside reverse transcriptase inhibitors; Pls; Protease inhibitors

Indexed keywords

ATAZANAVIR; EFAVIRENZ; LAMIVUDINE PLUS ZIDOVUDINE; LOPINAVIR PLUS RITONAVIR; NEVIRAPINE; RITONAVIR; RNA DIRECTED DNA POLYMERASE INHIBITOR; VIRUS RNA;

ADULT; ARTICLE; CLINICAL ARTICLE; CLINICAL PROTOCOL; CLINICAL TRIAL; DIABETES MELLITUS; DIARRHEA; DRUG EFFICACY; DRUG SAFETY; DRUG SUBSTITUTION; DRUG TREATMENT FAILURE; DRUG WITHDRAWAL; FEMALE; GLUCOSE BLOOD LEVEL; HUMAN; HUMAN IMMUNODEFICIENCY VIRUS INFECTION; HYPERGLYCEMIA; HYPERLIPIDEMIA; MALE; MONOTHERAPY; PATIENT COMPLIANCE; PILOT STUDY; PRIORITY JOURNAL; SIDE EFFECT; VIROLOGY; VIRUS INHIBITION;

EID: 33845716442     PISSN: 15284336     EISSN: None     Source Type: Journal    
DOI: 10.1310/hct0705-237     Document Type: Article

References (45)

1. Bartlett JG, Lane HG. Panel on Clinical Practices for Treatment of HIV infection, convened by the Department of Health and Human Services (DHHS). Guidelines for the Use of Antiretroviral Agents in HIV-Infected Adults and Adolescents, October 2005. Available at: http://www.aidsinfo.nih.gov/guidelines/. Accessed November 15, 2005.
2. Palella FJ, Jr, Delaney KM, Moorman, AC, et al. Declining morbidity and mortality among patients with advanced human immunodeficiency virus infection. N Engl J Med. 1998:338 (13):853-860.
3. Lewis W. Nucleoside reverse transcriptase inhibitors, mitochondrial DNA and AIDS therapy. Antivir Ther. 2005;10(suppl 2):M13-27.
4. Nolan D, Mallal S. Complications associated with NRTI therapy: update on clinical features and possible pathogenic mechanisms. Antivir Ther. 2004;9(6):849-863.
5. Galluzzi L, Pinti M, Guaraldi G, et al. Altered mitochondrial RNA production in adiopocytes from HIV-infected individuals with lipodystrophy. Antivir Ther. 2005;10(suppl 2):M91-99.
6. Antinori A, Zaccarelli M, Cingolani A, et al. Cross-resistance among nonnucleoside reverse transcriptase inhibitors limits recycling efavirenz after nevirapine failure. AIDS Res Hum Retroviruses. 2002;18(12):835-838.
7. Bozzette SA, Joyce G, McCaffrey DF, et al. Expenditures for the care of HIV-infected patients in the era of highly active antiretroviral therapy. N Engl J Med. 2001;344(11):817-823.
8. Havlir DV, Marschner IC, Hirsch MS, et al. Maintenance antiretroviral therapies in HIV infected patients with undetectable plasma HIV RNA after triple-drug therapy. AIDS Clinical Trials Group Study 343 Team. N Engl J Med. 1998;339(18):1261-1268.
9. Pialoux G, Raffi F, Brun-Vezinet F, 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. N Engl J Med. 1998;339:1269-1276.
10. Reijers MH, Weverlling GJ, Jurriaans S, et al. Maintenance therapy after quadruple induction therapy in HIV-1 infected individuals: Amsterdam Duration of Antiretroviral Medication (ADAM) study. Lancet. 1998;352:185-190.
11. Arieux C, Tattevin P, Souala FM, et al. Salvage therapy with amprenavir and ritonavir: prospective study in 17 heavily pretreated patients. HIV Clin Trials. 2002;3(2):125-132.
12. Duval X, Lamotte C, Race E, et al. Amprenavir inhibitory quotient and virological response in human immunodeficiency virus-infected patients on an amprenavir-containing salvage regimen without or with ritonavir. Antimicrob Agents Chemother. 2002;46(2):570-574.
13. Eron JJ, Feinberg J, Kessler HA, et al. Once-daily versus twice-daily lopinavir/ritonavir in antiretroviral-naïve HIV-positive patients: a 48-week randomized clinical trial. J Infect Dis. 2004;189(2):265-272.
14. Hicks C, King MS, Gulick RM, et al. Long-term safety and durable antiretroviral activity of lopinavir/ritonavir in treatment-naïve patients: 4 year follow-up study. AIDS. 2004:18(5):775-779.
15. Cvetkovic RS, Goa KL. Lopinavir/ritonavir: a review of its use in the managment of HIV infection. Drugs. 2003;63(8):769-802.
16. Perno CF, Cozzi-Lepri A, Balotta C, et al. Low prevalence of primary mutations associated with drug resistance in antiviral-naïve patients at therapy initiation. AIDS. 2002:16:619-624.
17. Hsu A, Kempf D, Granneman R, et al. Exploring theoretical mechanisms for lack of resistance to lopinavir/ritonavir in antiretroviral naïve subjects [abstract 436-W]. In: Program and abstracts of the 9th Conference on Retroviruses and Opportunistic Infections, Seattle. Alexandria, VA: Foundation for Retrovirology and Human Health; 2002:217.
18. Walsh JC, Mandalia, S, Gazzard, BG. Responses to a 1 month self-report on adherence to antiretroviral therapy are consistent with electronic data and virological treatment outcome. AIDS. 2002;16(2):269-277.
19. Ruane P, Luber A, Gaultier C, et al. Maintenance therapy using lopinavir/ ritonavir (LPV/r) alone for patients with well controlled HIV-infection. In: Program and abstracts of the XV International AIDS Conference; July 11-16, 2004; Bangkok, Thailand. Abstract TuPeB4638
20. Campo RE, Lalanne R, Tanner TJ, et al. Lopinavir/ritonavir maintenance monotherapy after successful viral suppression with standard highly active antiretroviral therapy in HIV-1-infected patients. AIDS. 2005;19:447-452.
21. Arribas JR, Pulido F, Lorenzo A, 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). J Acquir Immune Defic Syndr. 2005;40(3):280-287.
22. Gathe JC, Jr., Washington MY, Mayberry C, et al. IMANI-1 TC3WP single drug HAART-proof of concept study. Pilot study of the safety and efficacy of Kaletra (LPV/r) as single drug HAART in HIV + ARV-naïve patients-interim analysis of subjects completing final 48 week data. In: Program and abstracts of the XV International AIDS Conference; July 11-16, 2004; Bangkok, Thailand. Abstract MoOrB1057.
23. Pierone G, Mieras J, Kantor C, et al. Lopinavir/r as sole therapy for HIV-infection. In: Program and abstracts of the 9th European AIDS Conference; October 25-29, 2003; Warsaw, Poland. Abstract oral presentation Forum 1/5.
24. Pierone G, Mieras J, Kantor C, et al. Genotypic and phenotypic resistance observations among patients with viremia while on lopinavir/ ritonavir monotherapy. In: Program and abstracts of the 44th Interscience Conference on Antimicrobial Agents and Chemotherapy; 2004; Washington, DC. Abstract H-183.
25. Delfraissy J-F, Flandre P, Delaugerre C, et al. MONARK Trial (MONotherapy AntiRetroviral Kaletra): 48-week analysis of lopinavir/ ritonavir (LPV/R) monotherapy compared to LPV/R + zidovudine/lamivudine (AZT/3TC) in antiretroviral-naïve patients. In: Program and abstracts of the XVI International AIDS Conference; August 13-18, 2006; Toronto, Canada.
26. Nunes WP, Oliveira MS, Almeida MMTB, et al. 48-week efficacy and safety results of simplification to single agent lopinavir/ritonavir (LPV/r) regimen in patients suppressed below 80 copies/mL on HAART-the KalMo study in antiretroviral-naïve patients. In: Program and abstracts of the XVI International AIDS Conference; August 13-18, 2006; Toronto, Canada.
27. Cameron W, da Silva B, Arribas J, et al. A two-year randomized controlled clinical trial in antiretroviral-naïve subjects using lopinavir/ritonavir (LPV/r) monotherapy after initial induction treatment compared to an efavirenz (EFV) 3-drug regimen (Study MO3-613) in antiretroviral-naïve patients. In: Program and abstracts of the XVI International AIDS Conference; August 13-18, 2006; Toronto, Canada.
28. Arribas J, Pulido F, Delgado R, et al. Lopinavir/ritonavir as single-drug maintenance therapy in patients with HIV-1 suppression: forty-eight week results of a randomized, controlled, open label, clinical trial (OKO4 Study) in antiretroviral-naïve patients. In: Program and abstracts of the XVI International AIDS Conference; August 13-18, 2006; Toronto, Canada.
29. Kempf D, King M, Bernstein B, et al. Incidence of resistance in a double-blind study comparing lopinavir/ritonavir plus stavudine and lamivudine to nelfinavir plus stavudine and lamivudine. J Infect Dig. 2004;189:51-60.
30. Murphy R. Seven year follow-up of a lopinavir/ritonavir (LPV/r)-based regimen in antiretroviral (ARV) naïve subjects. In: Program and abstracts of the 10th European AIDS Conference; November 17-20, 2005; Dublin, Ireland.
31. Johnson VA, Brun-Vezinet F, Clotet B, et al. Update of the drug resistance mutations in HIV-1. Top HIV Med. 2006;14(3):125-130.
32. Friend J, Parkin N, Liegler T, et al. Isolated lopinavir resistance after virological rebound of a ritonavir/lopinavir-based regimen. AIDS. 2004;18:1965-1970.
33. Conradie F, Sanne I, Venter W, et al. Failure of lopinavir-ritonavir (Kaletra)-containing regimen in an antiretroviral-naïve patient. AIDS. 2004;18(7):1084-1085.
34. Goelz J, Wolf E, Moll A, et al. Single agent HAART with lopinavir/r (LPV/ r) in ART-naïve and pre-treated HIV-1-infected patients. In: Program and abstracts of the XVI International AIDS Conference; August 13-18, 2006; Toronto, Canada.
35. Norton M, Delaugere C, Batot G, et al. Drug resistance outcomes in a trial comparing lopinavir/ritonavir (LPV/r) monotherapy to LPV/r + zivudine/lamivudine (MONARK trial. In: Program and abstracts of the XV International HIV Drug Resistance Workshop; June 13-17, 2006; Stiges, Spain. Abstract 74.
36. Zhang YM, Imamichi H, Imamichi T, et al. Drug resistance during indinavir therapy is casued by mutations in the protease gene and its Gag substrate cleavage sites. J Virol. 1997;71(9):6662-6670.
37. Maguire MF, Guinea R, Griffin P, et al. Changes in human immunodeficiency virus type 1 Gag at positions L449 and P453 are linked to I50V protease mutants in vivo and cause reduction of sensitivity to amprenavir and improved viral fitness in vitro. J Virol. 2002;76(5):7398-7406.
38. Malet I, Roquebert B, Dalban C, et al. Association of Gag cleavage sites to protease mutations and to virological response in HIV-1 treated patients. J Infect. 2006; Jul 25. Epub ahead of print.
39. Solas C, Lafeuillade A, Halfon P, et al. Discrepancies between protease inhibitor concentrations and viral load in reservoirs and sanctuary sites in human immunodeficiency virus-infected patients. Antimicrob Agents Chemother. 2003;47:238-243.
40. Lafeuillade A, Solas C, Halfon P, et al. Differences in the detection of three HIV-1 protease inhibitors in non-blood compartments: clinical correlations. HIV Clin Trials. 2002;3:27-35.
41. Van den Brande G, Beck JM, Capparelli E, et al. Kaletra independently reduces HIV replication in cerebrospinal fluid. In: Program and abstracts of the 12th Conference on Retroviruses and Opportunististic Infections; February 22-25, 2005; Boston, Massachusetts. Abstract 403.
42. Capparelli EV, Holland D, Okamoto C, et al. Lopinavir concentrations in cerebrospinal fluid exceed the 50% inhibitory concentration for HIV. AIDS. 2005;19:949-952.
43. http://www.drugstore.com. Accessed January 15, 2006.
44. Escobar I, Pulido F, Arribas JR, et al. Pharmacoeconomic analysis of lopinavir/ritonavir mono-therapy as maintenance therapy in HIV-infected patients. In: Program and abstracts of the 11th European AIDS Conference; November 17-20, 2005; Dublin, Ireland. Abstract PE19.5/2.
45. Zhu T, Chiu Y, Doan T, et al. New tablet formulation of lopinavir/ ritonavir is bioequivalent to the capsule at a dose of 800/200 mg. In: Program and abstracts of the 45th Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC); December 16-19, 2005; Washington, DC.