Combination Treatment Using Capravirine (AG1549), Nelfinavir, and Two Nucleoside Reverse Transcriptase Inhibitors in HIV Patients Who Failed Initial Combination Therapy

A Phase II, Single-Blind, Randomized, Placebo-Controlled Study of Capravirine (AG1549) in Combination With Viracept and Two Nucleoside Reverse Transcriptase Inhibitors in HIV-Infected Subjects Who Failed an Initial Nonnucleoside Reverse Transcriptase Inhibitor Containing Regimen

The purpose of this study is to look at the effectiveness of an anti-HIV drug combination that adds capravirine in patients who have failed their first drug combination treatment.

[Note: As of 2/28/2001, due to toxicity studies and concern for safety, changes in the methodology were implemented and patients need to sign new informed consents. The study is unblinded. Group 1 receives AG1549; Group 2 receives an AG1549 placebo. Patients who are taking capravirine and who currently have viral loads below 400 copies/ml may continue to take capravirine at 1400 mg twice daily. Capravirine will be discontinued in patients with viral loads greater than 400 copies/ml at their last visit and they will be switched to new therapies or continue with their background therapies as deemed appropriate by the investigators.] Both groups also receive nelfinavir mesylate and 2 NRTIs. All patients receive the same dose of nelfinavir mesylate. The NRTIs are selected at the investigator's discretion provided the patient has not previously received the chosen NRTIs. Patients have regular physical examinations. Blood samples are collected regularly and at 1 month post-treatment to determine plasma HIV RNA, pharmacokinetics, and CD4 and CD8 counts. Patients who complete 24 weeks of treatment will have the option to continue treatment for an additional 24 weeks or end participation.

Inclusion Criteria

Patients may be eligible for this trial if they:

• Are HIV-positive.
• Have a CD4 cell count more than 50/mm3.
• Are at least 18 years old.
• Have adequate blood, kidney, and liver functions.
• Are currently taking an anti-HIV drug combination of an NNRTI plus 1 or more NRTIs for more than 28 days and are failing that combination.

Exclusion Criteria

Patients will not be eligible for this trial if they:

• Have had any protease inhibitor or capravirine treatment.
• Have been given any drug that interferes with their immune system or with the study drugs within 28 days of study entry.
• Have had radiation therapy within 28 days of study entry.