INDICATIONS AND USAGE
AGENERASE (amprenavir) is indicated in combination with other antiretroviral agents for the treatment of HIV-1 infection.
The following points should be considered when initiating therapy with AGENERASE:
In a study of NRTI-experienced, protease inhibitor-naive patients, AGENERASE was found to be significantly less effective than indinavir (see Description of Clinical Studies).
Mild to moderate gastrointestinal adverse events led to discontinuation of AGENERASE primarily during the first 12 weeks of therapy (see ADVERSE REACTIONS).
There are no data on response to therapy with AGENERASE in protease inhibitor-experienced patients.
Description of Clinical Studies
Therapy-Naive Adults
PROAB3001, a randomized, double-blind, placebo-controlled, multicenter study, compared treatment with AGENERASE Capsules (1,200 mg twice daily) plus lamivudine (150 mg twice daily) plus zidovudine (300 mg twice daily) versus lamivudine (150 mg twice daily) plus zidovudine (300 mg twice daily) in 232 patients. Through 24 weeks of therapy, 53% of patients assigned to AGENERASE/zidovudine/lamivudine achieved HIV-1 RNA <400 copies/mL. Through week 48, the antiviral response was 41%. Through 24 weeks of therapy, 11% of patients assigned to zidovudine/lamivudine achieved HIV-1 RNA <400 copies/mL. Antiviral response beyond week 24 is not interpretable because the majority of patients discontinued or changed their antiretroviral therapy.
NRTI-Experienced Adults
PROAB3006, a randomized, open-label multicenter study, compared treatment with AGENERASE Capsules (1,200 mg twice daily) plus NRTIs versus indinavir (800 mg every 8 hours) plus NRTIs in 504 NRTI-experienced, protease inhibitor-naive patients, median age 37 years (range 20 to 71 years), 72% Caucasian, 80% male, with a median CD4 cell count of 404 cells/mm3 (range 9 to 1,706 cells/mm3) and a median plasma HIV-1 RNA level of 3.93 log10 copies/mL (range 2.60 to 7.01 log10 copies/mL) at baseline. Through 48 weeks of therapy, the median CD4 cell count increase from baseline in the amprenavir group was significantly lower than in the indinavir group, 97 cells/mm3 versus 144 cells/mm3, respectively. There was also a significant difference in the proportions of patients with plasma HIV-1 RNA levels <400 copies/mL through 48 weeks (see Figure 1 and Table 5).
Figure 1. Virologic Response Through Week 48, PROAB3006*,†
HIV-1 RNA status and reasons for discontinuation of randomized treatment at 48 weeks are summarized (Table 5).
Table 5. Outcomes of Randomized Treatment Through Week 48 (PROAB3006) |
Outcome
|
AGENERASE
(n = 254)
|
Indinavir
(n = 250)
|
|
HIV-1 RNA <400 copies/mL*
|
30%
|
49%
|
|
HIV-1 RNA ≥400 copies/mL†,‡
|
38%
|
26%
|
|
Discontinued due to adverse events*,‡
|
16%
|
12%
|
|
Discontinued due to other reasons‡,§
|
16%
|
13%
|
* Corresponds to rates at Week 48 in Figure 1.
†Virological failures at or before Week 48.
‡Considered to be treatment failure in the analysis.
§Includes discontinuations due to consent withdrawn, loss to follow-up, protocol violations, non-compliance, pregnancy, never treated, and other reasons.
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