General Information

Reyataz (atazanavir, BMS-232632) is a type of antiretroviral agent called a protease inhibitor (PI). These medicines block protease, a protein that HIV needs to make more copies of itself.

Reyataz is indicated in combination with other antiretroviral agents for the treatment of HIV-1 infection. Reyataz does not cure HIV or prevent passing HIV to others.

Reyataz Capsules are available for oral administration in strengths containing the equivalent of 100 mg, 150 mg or 200 mg.

Pretreatment testing: Renal laboratory testing should be performed in all patients prior to initiation of Reyataz and continued during treatment with Reyataz. Hepatic testing should be performed in patients with underlying liver disease prior to initiation of Reyataz and continued during treatment with Reyataz.

• Treatment-naive adults: Reyataz 300 mg with ritonavir 100 mg once daily with food or Reyataz 400 mg once daily with food.
• Treatment-experienced adults: Reyataz 300 mg with ritonavir 100 mg once daily with food.
• Pediatric patients: Reyataz capsule dosage is based on body weight not to exceed the adult dose and must be taken with food.
• Pregnancy: Reyataz 300 mg with ritonavir 100 mg once daily with food, with dosing modifications for some concomitant medications.

Reyataz oral powder:

• Reyataz oral powder is for use in treatment-naive or treatment-experienced pediatric patients who are at least 3 months of age and weighing at least 5 kg. Reyataz oral powder must be mixed with food or a beverage for administration and ritonavir must be given immediately afterwards.

Dosing modifications: may be required for concomitant therapy, renal impairment and hepatic impairment

Mechanism of Action

Atazanavir, an azapeptide HIV-1 protease inhibitor, selectively inhibits the virus-specific processing of viral Gag and Gag-Pol polyproteins in HIV-1 infected cells, preventing formation of mature virions. Atazanavir exhibits anti-HIV-1 activity with a mean EC50 in the absence of human serum of 2 to 5 nM against a variety of laboratory and clinical HIV-1 isolates grown in peripheral blood mononuclear cells, macrophages, CEM-SS cells, and MT-2 cells.

Side Effects

Adverse events associated with the use of Reyataz may include (but are not limited to) the following:

• Headache
• Nausea
• Rash
• Abdominal pain
• Jaundice
• Vomiting
• Diarrhea

Clinical Trial Results

FDA approval of Reyataz was based on three randomized phase III studies. The first (study AI424-034) was a randomized, double-blind, multicenter trial comparing Reyataz (400mg) to efavirenz (600mg) once daily, each in combination with fixed-dose lamivudine (150) + zidovudine (300mg) twice daily. The study enrolled 810 antiretroviral treatment-naive subjects for 48 weeks. Subject had a mean age of 34 years, 36% were Hispanic, 33% were Caucasian, and 65% were male.

Result showed that 67% of subjects in the Reyataz plus lamivudine/zidovudine group responded to treatment compared with 62% of subjects in the efavirenz plus lamivudine/zidovudine group. Response was based on subjects that achieved and maintained confirmed HIV RNA <400 copies/mL through all 48 weeks. Data also demonstrated that 20% of subjects in the Reyataz plus lamivudine/zidovudine group achieved virologic failure compared with 21% of subjects in the efavirenz plus lamivudine/zidovudine group. Virologic failure subjects had confirmed viral rebound and failure to achieve confirmed HIV RNA <400 copies/mL through all 48 weeks.

The second study (AI424-008) was a randomized, multicenter trial, blinded trial comparing Reyataz (400 mg) once daily to Reyataz (600 mg) once daily. It also compared Reyataz to nelfinavir (1250 mg) twice daily, each in combination with stavudine and lamivudine twice daily. The trial enrolled 467 antiretroviral treatment-naive subject for 48 weeks. Subjects had a mean age of 35 years, 55% were Caucasian and 63% were male.

Results showed that 67% of subjects in the Reyataz plus lamivudine/stavudine group responded to treatment compared with 59% of subjects in the nelfinavir plus lamivudine/stavudine group. Response was based on subjects that achieved and maintained confirmed HIV RNA <400 copies/mL through all 48 weeks. Data also demonstrated that 24% of subjects in the Reyataz plus lamivudine/zidovudine group achieved virologic failure compared with 27% of subjects in the efavirenz plus lamivudine/zidovudine group. Virologic failure subjects had confirmed viral rebound and failure to achieve confirmed HIV RNA <400 copies/mL through all 48 weeks.

The Third study (AI424-043) was a randomized, open-label, multicenter comparing Reyataz (400 mg) once daily to lopinavir + ritonavir (400/100 mg) twice daily, each in combination with two nucleosides (NRTIs). The trial enrolled 300 subjects who experienced virologic failure to only one prior PI-containing regimen. For the 229 patients who have been assessed for efficacy, the mean time of prior exposure to antiretrovirals was 140 weeks for PIs, 180 weeks for NRTIs, and 85 weeks for NNRTIs (13% of patients). The mean age was 38 years where 53% were Hispanic, 41% were Caucasian, and 81% were male.

Results showed that 54% of subjects in the Reyataz plus two NRTIs group responded to treatment (HIV RNA <400 copies/mL) compared with 75% of subjects in the lopinavir + ritonavir plus two NRTIs group.