The Effectiveness of Ritonavir Plus Zidovudine Plus Lamivudine in HIV-Infected Patients

Summary

To determine whether administration of a highly active antiretroviral treatment regimen consisting of ritonavir (ABT-538), zidovudine (AZT), and lamivudine (3TC) is associated with the restoration of delayed type hypersensitivity and lymphocyte proliferative responses in patients with moderately advanced HIV-1 infection. To better characterize in these patients the phenotype of the expanded lymphocyte subpopulations, as well as the genotype, phenotype, and cellular origin of viruses that persist after initiation of therapy, and the genotype and phenotype of drug-resistant isolates that emerge during therapy. Although plasma viral load drops dramatically after initiation of powerful antiretrovirals, it does not drop to zero. It appears that a new steady state is reached, suggesting that a reservoir may exist of virus-producing cells, possibly cells of monocyte/macrophage lineage, that continue to produce a low level of virus despite antiretroviral treatment.

Timeline

Start

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Primary completion

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Completion

2007-07

Publications

• Background Connick E, Lederman MM, Kotzin BL, Spritzler J, Kuritzkes DR, St Clair M, Sevin AD, Fox L, Chiozzi MH, Leonard JM, Rousseau F, D'Arc Roe J, Martinez A, Kessler H, Landay A. Immune reconstitution in the first year of potent antiretroviral therapy and its relationship to virologic response. J Infect Dis. 2000 Jan;181(1):358-63. doi: 10.1086/315171.
• Background Lederman MM, Connick E, Landay A, Kuritzkes DR, Spritzler J, St Clair M, Kotzin BL, Fox L, Chiozzi MH, Leonard JM, Rousseau F, Wade M, Roe JD, Martinez A, Kessler H. Immunologic responses associated with 12 weeks of combination antiretroviral therapy consisting of zidovudine, lamivudine, and ritonavir: results of AIDS Clinical Trials Group Protocol 315. J Infect Dis. 1998 Jul;178(1):70-9. doi: 10.1086/515591.
• Background Kaushal S, Landay AL, Lederman MM, Connick E, Spritzler J, Kuritzkes DR, Kessler H, Levine BL, St Louis DC, June CH. Increases in T cell telomere length in HIV infection after antiretroviral combination therapy for HIV-1 infection implicate distinct population dynamics in CD4+ and CD8+ T cells. Clin Immunol. 1999 Jul;92(1):14-24. doi: 10.1006/clim.1999.4726.
• Background Kuritzkes DR, Sevin A, Young B, Bakhtiari M, Wu H, St Clair M, Connick E, Landay A, Spritzler J, Kessler H, Lederman MM. Effect of zidovudine resistance mutations on virologic response to treatment with zidovudine-lamivudine-ritonavir: genotypic analysis of human immunodeficiency virus type 1 isolates from AIDS clinical trials group protocol 315.ACTG Protocol 315 Team. J Infect Dis. 2000 Feb;181(2):491-7. doi: 10.1086/315244.
• Background Doepel L, Folkers G. NIAID researchers present new findings at retrovirus meeting. National Institute of Allergy and Infectious Diseases. NIAID AIDS Agenda. 1997 Mar:4, 11.
• Background Shapiro HM, Lederman M, Connick E, Kessler H, Kuritzkes DR, Landay AL. Small differences in CD4+ T-cell production may go unnoticed. AIDS. 1999 Feb 4;13(2):290-1. doi: 10.1097/00002030-199902040-00025. No abstract available.
• Background ACTG 315 drug cocktail restores immune function. AIDS Patient Care STDS. 1997 Jun;11(3):193. doi: 10.1089/apc.1997.11.193. No abstract available.
• Background Wu H, Connick E, Kuritzkes DR, Landay A, Spritzler J, Zhang B, Spear GT, Kessler H, Lederman MM; ACTG 315 Team. Multiple CD4+ cell kinetic patterns and their relationships with baseline factors and virological responses in HIV type 1 patients receiving highly active antiretroviral therapy. AIDS Res Hum Retroviruses. 2001 Sep 1;17(13):1231-40. doi: 10.1089/088922201750461285.
• Background Lederman M, Connick E, Landay A, Kessler H, Kuritzkes D, St Clair M, Fox L, Heath-Chiozzi M, Rousseau F, Spritzler J. Partial immune reconstitution after 12 weeks of HAART (AZT, 3TC, ritonavir) preliminary results of ACTG 315. Conf Retroviruses Opportunistic Infect. 1997 Jan 22-26;4th:208 (abstract no LB13)
• Background Wu H, Kuritzkes DR, McClernon DR, Kessler H, Connick E, Landay A, Spear G, Heath-Chiozzi M, Rousseau F, Fox L, Spritzler J, Leonard JM, Lederman MM. Characterization of viral dynamics in human immunodeficiency virus type 1-infected patients treated with combination antiretroviral therapy: relationships to host factors, cellular restoration, and virologic end points. J Infect Dis. 1999 Apr;179(4):799-807. doi: 10.1086/314670.
• Gillespie EA, Gillespie BW, Stevens MJ. Painful diabetic neuropathy: impact of an alternative approach. Diabetes Care. 2007 Apr;30(4):999-1001. doi: 10.2337/dc06-1475. No abstract available.

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