Atazanavir for HIV-1 Infection Treatment: Recommended Use and Dosage
Atazanavir is indicated in combination with other antiretroviral agents for the treatment of HIV-1 infection in adults and pediatric patients 6 years and older weighing at least 15 kg, with recommended dosing of 300 mg once daily boosted with ritonavir 100 mg once daily for most patients. 1
Standard Dosing Recommendations
Treatment-Naïve Patients:
- Preferred regimen: Atazanavir 300 mg with ritonavir 100 mg once daily, combined with two nucleoside reverse transcriptase inhibitors (NRTIs) 2
- Alternative regimen (US only): Unboosted atazanavir 400 mg once daily with two NRTIs 3
- Must be taken with food to increase absorption (70% increase in bioavailability) 4
Treatment-Experienced Patients:
- Required regimen: Atazanavir 300 mg with ritonavir 100 mg once daily, combined with other antiretrovirals 3
- Selection should be guided by the number of baseline primary protease inhibitor resistance substitutions 1
Special Populations and Considerations
Pregnancy:
- Atazanavir/ritonavir is recommended during pregnancy (evidence rating: AIIa) 2
- Should be combined with either tenofovir disoproxil fumarate/emtricitabine or tenofovir disoproxil fumarate/lamivudine 2
HIV/HCV Co-infection:
- When treating HCV with direct-acting antivirals in HIV co-infected patients:
Tuberculosis Co-infection:
- Not recommended as first-line therapy for patients with HIV and active tuberculosis
- If a protease inhibitor must be used with rifampin-based TB treatment, rifabutin (150 mg/day) should be substituted for rifampin 2
- Integrase inhibitor-based regimens (dolutegravir, raltegravir) are preferred for TB co-infection 2
Drug Interactions and Contraindications
Major Drug Interactions:
- Contraindicated with: alfuzosin, amiodarone, astemizole, terfenadine, cisapride, ergot derivatives, lovastatin, simvastatin, oral midazolam, triazolam, quetiapine, quinidine, salmeterol, sildenafil (when used for pulmonary arterial hypertension) 2
- Acid-reducing agents: Proton pump inhibitors, H2 receptor antagonists, and antacids can significantly reduce atazanavir absorption 5
- Other antiretrovirals:
Monitoring Requirements:
- Monitor liver function tests due to potential hepatotoxicity
- Monitor for hyperbilirubinemia, which occurs in 22-47% of patients but rarely requires discontinuation (<2%) 5
- ECG monitoring recommended when used with rilpivirine 2
Clinical Advantages and Considerations
Advantages:
- Once-daily dosing (simplifies regimen) 4
- Favorable lipid profile compared to other protease inhibitors 6
- Low capsule burden 6
Key Considerations:
- Inhibits glucuronyltransferase, causing increased unconjugated bilirubin levels and potential jaundice 3
- Mean terminal elimination half-life is approximately 7 hours 4
- Ritonavir boosting increases atazanavir AUC by 3-4 fold and minimum plasma concentration by approximately 10-fold 4
Pitfalls to Avoid
- Never administer unboosted atazanavir to treatment-experienced patients
- Avoid co-administration with proton pump inhibitors
- Do not use with rifampin for TB treatment (use rifabutin if protease inhibitor is necessary)
- Take care with tenofovir co-administration due to potential for reduced atazanavir levels
- Always administer with food to ensure adequate absorption
When selecting HIV treatment regimens, newer integrase inhibitor-based regimens are often preferred over protease inhibitor-based regimens for many patients, but atazanavir remains a valuable option particularly when metabolic complications are a concern.