About The Study
The objective of this study was to evaluate the tolerance, safety and effectiveness of nevirapine in preventing clinical AIDS progression events or death when used in combination with lamivudine (3TC) and background nucleoside therapy.
This study was designed in 1995 and had the following restrictions: The stable background nucleoside therapy consisted of AZT, alone or in combination with ddC or ddI. AZT was required as part of the background treatment and could only be replaced with d4T in case of AZT intolerance. No change in background therapy was allowed prior the occurrence of a documented endpoint. Other nucleosides, non-nucleosides and protease inhibitors were excluded from the protocol. Volunteers who had received 3TC for longer than three months were also excluded. Eligible volunteers were randomized to treatment with open-label 3TC 150 mg bid plus nevirapine 200 mg once daily (qd) for two weeks and then 200 mg bid, or open-label 3TC 150 mg bid plus nevirapine-placebo qd for two weeks and then bid. Enrollment in this trial was limited to volunteers with a CD4+ cell count less than or equal to 200 cells/mm3.
During the course of the trial, findings from other trials, including CAESAR, Delta, and ACTG 175, compromised both accrual and retention of patients. The trial design failed to provide state-of-the-art treatment. Changes to the protocol were made to improve treatment options for participants. As a result, the trial population became heterogenous. Only half of the patients who entered the trial were nucleoside experienced but 3TC naïve. Thus the ability to demonstrate an overall clinical benefit of nevirapine using the entire trial population (2256 participants from North America, Europe, Australia and South Africa) became very low. Instead, an analysis was performed on the first hundred and fifty-four antiretroviral-naïve participants who used only AZT+3TC as background therapy. They were evaluated for viral response to Nevirapine + AZT+ 3TC vs. placebo + AZT + 3TC. The mean baseline viral load was 147 for the nevirapine group and 151 for the placebo group, while the mean CD4 cell count was 86 and 82 respectively. The viral load at entry was over 100,000 copies/mL in 58% of the participants and above 50,000 for 75%.
Using the limit of detection (LD) of 400 copies/mL, 86% of nevirapine recipients achieved a viral load below limit of detection (BLD), compared to 49% of placebo recipients. Among the nevirapine group, 68% of the volunteers observed at 12 months were still BLD. Nevirapine + AZT + 3TC was superior to the placebo + AZT + 3TC for all comparisons. Viral suppression to below the limit of detection of 50 at 12 months in the nevirapine recipients with high viral loads at entry was at least as favorable as in volunteers with lower viral loads at entry (42% BLD for viral loads higher than 100,000; 55% for viral loads below 100,000).
Nevirapine + AZT + 3TC is effective in suppression of HIV viral load for at least 12 months, in volunteers with advanced immunodeficiency and high pretreatment viral loads. The effect is as great in patients with high viral loads (>100,000 copies/mL) at entry.
Note: These results were taken from an abstract that was submitted to ICAAC 99.