INDICATIONS AND USAGE
NORVIR is indicated in combination with other antiretroviral agents for the treatment of HIV-infection. This indication is based on the results from a study in patients with advanced HIV disease that showed a reduction in both mortality and AIDS-defining clinical events for patients who received NORVIR either alone or in combination with nucleoside analogues. Median duration of follow-up in this study was 13.5 months.

Description of Clinical Studies
The activity of NORVIR as monotherapy or in combination with nucleoside reverse transcriptase inhibitors has been eva luated in 1446 patients enrolled in two double-blind, randomized trials.

Advanced Patients with Prior Antiretroviral Therapy
Study 247 was a randomized, double-blind trial (with open-label follow-up) conducted in HIV-infected patients with at least nine months of prior antiretroviral therapy and baseline CD4 cell counts ≤ 100 cells/µL. NORVIR 600 mg twice-daily or placebo was added to each patient's baseline antiretroviral therapy regimen, which could have consisted of up to two approved antiretroviral agents. The study accrued 1090 patients, with mean baseline CD4 cell count at study entry of 32 cells/µL. After the clinical benefit of NORVIR therapy was demonstrated, all patients were eligible to switch to open-label NORVIR for the duration of the follow-up period. Median duration of double-blind therapy with NORVIR and placebo was 6 months. The median duration of follow-up through the end of the open-label phase was 13.5 months for patients randomized to NORVIR and 14months for patients randomized to placebo.

The cumulative incidence of clinical disease progression or death during the double-blind phase of Study 247 was 26% for patients initially randomized to NORVIR compared to 42% for patients initially randomized to placebo. This difference in rates was statistically significant (see Figure 1).

Figure 1. Time to Disease Progression or Death During the Double-blind Phase of Study 247

The cumulative mortality through the end of the open-label follow-up phase for patients enrolled in Study 247 was 18% for patients initially randomized to NORVIR compared to 26% for patients initially randomized to placebo. This difference in rates was statistically significant (see Figure 2). Since the analysis at the end of the open-label phase includes patients in the placebo arm who were switched from placebo to NORVIR therapy, the survival benefit of NORVIR cannot be precisely estimated.

Figure 2. Survival of Patients by Randomized Treatment Regimen in Study247

Figure 3 and Figure 4 summarize the mean change from baseline for CD4 cell count and plasma HIV RNA (copies/mL), respectively, during the first 24 weeks for the double-blind phase of Study 247.

Figure 3. Mean Change from Baseline in CD4 Cell Count (cells/µL) During the Double-blind Phase of Study 247

Figure 4. Mean Change from Baseline in HIV RNA (log copies/mL) During the Double-blind Phase of Study 247

Patients Without Prior Antiretroviral Therapy
In Study 245, 356 antiretroviral-naive HIV-infected patients (mean baseline CD4=364cells/µL) were randomized to receive either NORVIR 600 mg twice-daily, zidovudine 200mgthree-times-daily, or a combination of these drugs. Figure 5 and Figure 6 summarize the mean change from baseline for CD4 cell count and plasma HIV RNA (c