The Effectiveness of Indinavir Plus Zidovudine Plus Lamivudine in HIV-Infected Patients With No Symptoms of Infection

Merck Sharp & Dohme (MSD)

Status and phase: Completed; Phase 4

Conditions: HIV Infections

Treatments: Drug: Lamivudine; Drug: Indinavir sulfate; Drug: Zidovudine

Study type: Interventional

Funder types: Industry

Identifiers

NCT00002179

MK-0639

246G

Details and patient eligibility

About

To evaluate the ability of the combination of indinavir, zidovudine, and lamivudine to suppress HIV-1 infection as measured by: (1) the maintenance of HIV-1 serum viral RNA below the limit of detection of the most sensitive validated assay (ultradirect assay) and (2) absence of evidence of infectious virus in lymph node, cerebrospinal fluid (CSF), peripheral mononuclear cells (PBMCs), and semen.

It is hypothesized that the administration of indinavir, zidovudine, and lamivudine will result in:

1. No evidence of infectious virus in lymph node tissue, CSF, PBMCs, and semen samples in 50% of patients who have undetectable viral RNA by the most sensitive validated assay available (ultradirect assay) for at least 48 weeks.
2. Sustained suppression of HIV-1 infection as measured by a decrease in serum viral RNA to below the limit of detection of the ultradirect assay for at least 48 weeks in at least 25% of patients.
3. Suppression of HIV-1 infection as measured by a decrease in serum viral RNA to below the limit of detection of the standard Amplicor assay (i.e., negative) in at least 90% of patients by Week 16.
4. Suppression of HIV-1 infection, suggesting eradication of the virus as measured by maintenance of serum viral RNA to below the limit of detection of the ultradirect assay for at least 24 weeks after discontinuation of indinavir, zidovudine, and lamivudine in patients who have maintained this level of suppression for at least 120 weeks on therapy.

Full description

It is hypothesized that the administration of indinavir, zidovudine, and lamivudine will result in:

1. No evidence of infectious virus in lymph node tissue, CSF, PBMCs, and semen samples in 50% of patients who have undetectable viral RNA by the most sensitive validated assay available (ultradirect assay) for at least 48 weeks.
2. Sustained suppression of HIV-1 infection as measured by a decrease in serum viral RNA to below the limit of detection of the ultradirect assay for at least 48 weeks in at least 25% of patients.
3. Suppression of HIV-1 infection as measured by a decrease in serum viral RNA to below the limit of detection of the standard Amplicor assay (i.e., negative) in at least 90% of patients by Week 16.
4. Suppression of HIV-1 infection, suggesting eradication of the virus as measured by maintenance of serum viral RNA to below the limit of detection of the ultradirect assay for at least 24 weeks after discontinuation of indinavir, zidovudine, and lamivudine in patients who have maintained this level of suppression for at least 120 weeks on therapy.

All patients receive indinavir plus zidovudine plus lamivudine for at least 96 weeks. If there is no evidence of infectious virus, and patients continue to have serum viral RNA levels below the limit of detection of the ultradirect assay for at least 96 weeks, therapy is continued for an additional 24 weeks. However, during this additional 24 weeks of therapy patients may continue to receive this triple combination drug regimen or make changes to this drug regimen treatment by reducing their number of antiretroviral agents. After 120 weeks, if patients continue to have serum viral RNA levels below the limit of detection of the ultradirect assay, patients discontinue all antiretroviral therapy. However, if there is any evidence of infectious virus, as outlined above, patients do not discontinue therapy. Patients who develop detectable serum viral RNA following discontinuation of therapy are given the option to reinitiate therapy with the triple combination of indinavir, zidovudine and lamivudine. NOTE: Patients who develop an intolerance to zidovudine may use stavudine at doses per body weight at the direction of the investigator.

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Inclusion Criteria

Patients must have:

• HIV-1 seropositive status.
• CD4 count >= 500 cells/mm3.
• Serum viral RNA level > 1000 copies/ml.

Exclusion Criteria

Prior Medication:

Excluded:

Previous antiretroviral therapy.