The purpose of this study is to see if the addition of capravirine to VIRACEPT (nelfinavir
mesylate) plus 2 nucleoside reverse transcriptase inhibitors (NRTIs) is an effective
combination drug therapy for HIV patients who have failed a nonnucleoside reverse
transcriptase inhibitor (NNRTI) therapy.
[Note: As of 2/28/2001, due to toxicity studies and concern for safety, patients need to
sign new informed consents. 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.] This study will take place
in approximately 150 centers in the US, Canada, Europe, Australia, Argentina, and South
Africa. Patients are randomized to 1 of 2 treatment groups and stratified by geographic
sites (North American and non-North American), plasma HIV-1 RNA levels, and prior NNRTI use.
Group 1 patients receive capravirine plus VIRACEPT plus 2 new NRTIs and Group 2 patients
receive capravirine placebo plus VIRACEPT plus 2 new NRTIs. NRTIs will not be provided by
the sponsor. Patients may remain on their assigned treatment for 48 weeks, with posttherapy
follow-up occurring at 1 and 3 months. Assessments, done at various times throughout the
study, include medical history, HIV antibody test, complete or symptom-directed physical
examination, vital signs, height, weight, serum pregnancy test, hematology, chemistry, and
recording of concomitant medications and adverse events. Other select assessments are
performed at specified visits. Plasma samples for resistance testing and blood specimens for
peripheral blood mononuclear cells (PBMC) are obtained at several times. The plasma samples
and PBMCs may be used for viral drug resistance testing. Blood samples for quantitation of
capravirine, VIRACEPT, and M8 (a metabolite of VIRACEPT) plasma concentrations are collected
several times. Additional blood samples for analysis of drug concentrations may be requested
depending on concomitant NRTIs or other medications. A Data Safety Monitoring Board monitors
patient safety at prescribed intervals during the study.
Patients may be eligible for this study if they:
- Are HIV positive.
- Are at least 18 years old.
- Are currently taking an NNRTI and at least 1 NRTI for at least 28 days and failing
that therapy. (Patients who began an NRTI therapy without an NNRTI and then added an
NNRTI may also enroll.)
- Are on the current NNRTI plus NRTI therapy at the time of the screening visit.
- Have a CD4 count greater than 50/mm3 and viral load greater than 2,000 copies/ml at
the screening visit.
- Have adequate blood, kidney, and liver functions.
- Agree to use a barrier method of birth control while on the study.
- Agree to use additional methods of birth control if less than 2 years postmenopausal.
Patients will not be eligible for this study if they:
- Are using or have received other investigative drugs within 28 days of receiving the
first dose of study drug.
- Are using or have received any medications or radiation treatments that interfere
with the study drug within 28 days of receiving the first dose of study drug.
- Have had prior treatment with capravirine or any protease inhibitors.
- Are pregnant or breast-feeding.
- Have an active infection or serious medical condition.
- Have a mental, social, or addictive disorder that may interfere with study treatment.