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

Sponsor

National Institute of Allergy and Infectious Diseases (NIAID) (NIH)

Overall Status

Completed

CT.gov ID

NCT00001075

Collaborator

(none)

Enrollment

Locations

18.3

Patients Per Site

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
HIV Infections	Drug: Ritonavir Drug: Lamivudine Drug: Zidovudine	N/A

Detailed Description

Patients undergo 5 weeks of antiretroviral washout before initiating therapy with ritonavir alone for 9 days, followed by combination therapy with ritonavir, zidovudine, and lamivudine from day 10 through week 48. [AS PER AMENDMENT 1/31/97: The availability of the current, open-label study treatment has been extended to allow patients who have completed 48 weeks of therapy to continue protocol therapy until the last enrolled patient completes 48 weeks of study treatment.]

Study Design

Study Type:

Interventional

Primary Purpose:

Treatment

Official Title:

A Pilot Study to Evaluate the Immunologic Consequences of a Highly Active Antiretroviral Therapy Regimen (HAART) Consisting of Ritonavir (ABT-538), Zidovudine (AZT), and Lamivudine (3TC) in Moderately Advanced HIV-1 Disease

Actual Study Completion Date :

Jul 1, 2007

Outcome Measures

Primary Outcome Measures

Eligibility Criteria

Criteria

Ages Eligible for Study:

16 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria

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.
Consent of parent or guardian if less than 18 years old.

Prior Medication:

Required:

Prior AZT at 500-600 mg bid at any time.
PCP prophylaxis during antiretroviral washout.

Allowed:

Prior ddI and/or ddC.
Prior recombinant erythropoietin and/or G-CSF for AZT-related bone marrow suppression.

Exclusion Criteria

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:

Active opportunistic infection or febrile illness with temperature >= 38.5 C within 3 days prior to study entry.
History of acute pancreatitis within the past 2 years.

Prior Medication:

Excluded:

Prior 3TC or a protease inhibitor.
Experimental drugs except those for HIV-related conditions, within the past 30 days.

[AS PER AMENDMENT 8/27/96: Immunization must be avoided prior to the antiretroviral washout period.]

Active substance abuse.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Colorado Hospital CRS	Aurora	Colorado	United States	80045
2	Rush Univ. Med. Ctr. ACTG CRS	Chicago	Illinois	United States	60612
3	Case CRS	Cleveland	Ohio	United States	44106