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

NCT00001075 | Completed

• 2 other identifiers: ACTG 31510688
• Study Type: interventional
• Target: 55
• Locations: 1 country
• Sites: 3

Brief 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.

Conditions

HIV Infections

Keywords

Drug Therapy, Combination; Acquired Immunodeficiency Syndrome; AIDS-Related Complex; Antiviral Agents; Zidovudine; HIV Protease Inhibitors; Ritonavir; Lamivudine

Interventions

Ritonavir DRUG

Lamivudine DRUG

Zidovudine DRUG

Eligibility Criteria

• Age: 16 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Concurrent Medication:
• Allowed:
• Recombinant erythropoietin and/or G-CSF for AZT-related bone marrow suppression.
• Antibiotics other than metronidazole.
• PCP prophylaxis.
• Regularly prescribed medications such as antipyretics, analgesics, allergy medicine, and oral contraceptives.
• Vitamins and herbal therapies.
• Concurrent Treatment:
• Allowed:
• Acupuncture.
• Visualization techniques.
• Patients must have:
• Documented HIV infection.
• CD4 count 100-300 cells/mm3.
• At least 3 consecutive months of prior AZT at a dosage of 500-600 mg bid, but with 5 weeks of antiretroviral washout prior to study entry.

You may not qualify if:

• Co-existing Condition:
• Patients with the following symptoms or conditions are excluded:
• Chronic pancreatitis.
• Psychological conditions that would affect compliance.
• Intolerance to 500-600 mg/day AZT.
• Concurrent participation on another antiretroviral research treatment study (study treatment for opportunistic infection or complications of HIV is allowed).
• Considered likely to be noncompliant on study.
• Concurrent Medication:
• Excluded:
• Immunomodulators such as systemic corticosteroids, thalidomide, or cytokines.
• Rifabutin.
• Disulfiram (Antabuse) or other medications with similar effects, including metronidazole.
• Other drugs contraindicated with ritonavir.
• \[AS PER AMENDMENT 8/27/96: Immunization must be avoided during the antiretroviral washout period.\]
• Patients with the following prior conditions are excluded:

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead

Study Sites (3)

University of Colorado Hospital CRS

Aurora, Colorado, 80045, United States

Location

Rush Univ. Med. Ctr. ACTG CRS

Chicago, Illinois, 60612, United States

Location

Case CRS

Cleveland, Ohio, 44106, United States

Location

Related Publications (11)

• 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.

  PMID: 10608789 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.

  PMID: 9652425 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.

  PMID: 10413649 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.

  PMID: 10669331 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.

  PMID: 11364173 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.

  PMID: 10202843 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.

  PMID: 11361794 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.

  PMID: 11559422 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.

  PMID: 10068574 BACKGROUND

• 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.

  PMID: 17392561 DERIVED

MeSH Terms

Conditions

HIV Infections; Acquired Immunodeficiency Syndrome; AIDS-Related Complex

Interventions

Ritonavir; Lamivudine; Zidovudine

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases; Slow Virus Diseases

Intervention Hierarchy (Ancestors)

Thiazoles; Sulfur Compounds; Organic Chemicals; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Zalcitabine; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Dideoxynucleosides; Thymidine

Study Officials

• Lederman M

  STUDY CHAIR

• Kessler H

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: not applicable
• Purpose: TREATMENT
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 2, 1999
• First Posted: August 31, 2001
• Study Completion: July 1, 2007
• Last Updated: November 4, 2021

Record last verified: 2021-10

Locations

US (3)