Combination Therapy: This is a combination therapy for HIV-1 infection, consisting of two separate active ingredients: Atazanavir (A), an HIV protease inhibitor, and Ritonavir (B), a pharmacokinetic boosting agent.
Standard Adult Dosing: The standard adult dose is one Atazanavir 300 mg tablet and one Ritonavir 100 mg tablet taken together, typically once daily.
Pharmacokinetic Booster: Ritonavir is included at a low dose not for its direct antiviral effect, but to inhibit the metabolism of Atazanavir, thereby increasing its concentration in the bloodstream.
Component of cART: This combination is a core component of combination antiretroviral therapy (cART) and must be used with other antiretroviral agents to provide a complete and effective treatment regimen.
Advantages
Once-Daily Dosing: The pharmacokinetic boosting effect of Ritonavir allows for a once-daily dosing regimen, which significantly simplifies the treatment schedule and improves patient adherence.
High Efficacy: The boosted concentration of Atazanavir provides potent and sustained viral suppression, making it a highly effective component of a cART regimen.
Lower Impact on Lipids: Compared to some other protease inhibitor-based regimens, Atazanavir is associated with a lower risk of increasing total cholesterol and triglycerides.
High Barrier to Resistance: As a potent protease inhibitor, Atazanavir has a high genetic barrier to resistance, meaning the virus is less likely to develop mutations that would render the drug ineffective.
Uses
HIV-1 Infection: Indicated for the treatment of HIV-1 infection in adults and in children weighing at least 35-40 kg, in combination with other antiretroviral agents.
Treatment-Naïve and -Experienced Patients: It is effective in both patients who are new to HIV treatment and those who have failed previous regimens.
Post-Exposure Prophylaxis (PEP): This combination is a recommended component of PEP regimens to prevent HIV infection following a potential exposure.
Use in Pregnancy: It is a key regimen for managing HIV in pregnant women to prevent perinatal transmission, with specific dosing recommendations.
Nature
Drug Classes: Atazanavir is a protease inhibitor (PI) and Ritonavir is also a PI, but it is primarily used as a cytochrome P450 (CYP450) inhibitor.
Mechanism of Action (Atazanavir): Atazanavir works by selectively inhibiting the viral enzyme protease, which is essential for the cleavage of viral polyproteins into functional proteins. This results in the production of immature, non-infectious viral particles.
Mechanism of Action (Ritonavir): At a low dose, Ritonavir is a potent inhibitor of the CYP3A4 enzyme in the liver. By blocking this enzyme, it prevents the rapid metabolism of Atazanavir, leading to higher and more sustained therapeutic concentrations.
Side Effects: A key characteristic of Atazanavir is its association with asymptomatic, reversible increases in indirect bilirubin, which can cause jaundice or yellowing of the eyes. This is due to its inhibition of the enzyme UGT1A1.
Storage
Temperature: Store the tablets at a controlled room temperature, typically between 20∘C to 25∘C (68∘F to 77∘F).
Protection: Keep the tablets in their original, tightly closed container, protected from light and moisture.
Administration: Both Atazanavir and Ritonavir tablets must be taken with food to enhance their absorption and efficacy.
Patient Compliance: Patients must be educated on the importance of taking every dose as prescribed and on time to prevent the development of viral resistance and to ensure long-term treatment success.
