A Randomized Trial of the Efficacy and Safety of a Strategy of Starting With Nelfinavir Versus Ritonavir Added to Background Antiretroviral (AR) Nucleoside Therapy in HIV-Infected Individuals With CD4+ Cell Counts Less Than or Equal to 200/mm3

• Status: Completed
• Trial end date: 2001-12-01
• Target enrollment: 0
• Participant gender: All

Summary

To compare nelfinavir (NFV) with ritonavir (RTV) for delaying disease progression or death in HIV-infected patients with CD4+ cell counts less than 100 cells/mm3 [AS PER AMENDMENT 3/11/98: less than or equal to 200 cells/mm3]. To compare NFV with RTV for the development of adverse events and for rates of permanent discontinuation of study medication.

[AS PER AMENDMENT 10/02/97: To compare by intention-to-treat analysis for disease progression, including death, the following two regimens: NFV plus background combination antiretroviral (AR) therapy followed by indinavir (IDV) or RTV in the event of significant intolerance; and RTV plus AR therapy followed by IDV, then NFV, in the event of significant intolerance.] [AS PER AMENDMENT 3/11/98: SUBSTUDY CPCRA 045: To determine the relative rates of emergence of HIV-1 resistance and to compare changes in plasma HIV RNA levels and CD4+ cell counts in a sample of patients with CD4+ cell counts <= 200/mm3 who are enrolled in protocol CPCRA 042.] AR therapy is rapidly becoming the standard of care for the treatment of HIV infection. AR therapy provides the best opportunity for maximizing viral suppression, reducing toxicity and delaying the emergence of resistant strains. The newest class of AR agents, the HIV protease inhibitors, exhibits the most potent anti-HIV effects described to date. This study will compare 2 protease inhibitors, NFV and RTV for efficacy and safety in a population with advanced HIV disease, who are taking various background nucleoside therapies.

• Phase: N/A
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
• Treatments: Indinavir; Nelfinavir; Ritonavir

Criteria

Inclusion Criteria

Concurrent Medication:

• Background AR nucleoside therapy is required, although background AR therapy may also be no background therapy. However, the use of protease inhibitors is not recommended as monotherapy unless there is no other alternative. Therefore, patients who are not on AR treatment may be enrolled at the discretion of the clinician.

Allowed:

• Saquinavir.

Patients must have:

• Documented HIV infection.

• A CD4+ cell count <= 100/mm3 within 3 months prior to the study. [AS PER AMENDMENT 3/11/98: CD4+ cell count <= 200/mm3 any time prior to entry].

• Parental consent if patient is < 18 years old.

Prior Medication:

Allowed:

• Saquinavir (SQV).

Exclusion Criteria

Co-existing Condition:

Patients with the following symptoms or conditions are excluded:

• Stage 2 or greater AIDS dementia complex.

• [AS PER AMENDMENT 10/2/97: Any acute disease or condition that would, in the physician's judgement, contraindicate starting NFV or RTV.]

• Known hypersensitivity to RTV or any of its ingredients (for patients assigned to RTV therapy).

Concurrent Medication:

Excluded:

• Concomitant use of protease inhibitors.

• Concomitant treatments that cannot be discontinued, and in the physician's judgement, should not be taken with NFV or RTV.

AS PER AMENDMENT 10/2/97:

• For patients randomized to NFV:

• Concomitant therapy with terfenadine, astemizole, cisapride, triazolam, midazolam, ergot derivatives, amiodarone, quinidine, or rifampin.

For patients randomized to IDV:

• Concomitant therapy with terfenadine, astemizole, cisapride, triazolam, midazolam, and rifampin.

Patients with any of the following prior symptoms are excluded:

AS PER AMENDMENT 10/2/97:

• History of clinically significant hypersensitivity reaction to any component of NFV tablets (for patients assigned to NFV therapy).

Prior Medication:

Excluded:

• Prior use of protease inhibitors except SQV.

[AS PER AMENDMENT 10/2/97:

• Prior use of IDV for more than 4 weeks or other protease inhibitors (except SQV) for any prior duration.]