Combination Therapy: This is a combination therapy for HIV-1 infection, consisting of two separate active ingredients: Darunavir (A), an HIV protease inhibitor, and Ritonavir (B), a pharmacokinetic boosting agent.
Standard Adult Dosing: This regimen, with Darunavir 600 mg and Ritonavir 100 mg, is the standard oral dose for adults who are treatment-experienced or pregnant. It is typically administered twice daily.
Pharmacokinetic Booster: Ritonavir is included at a low dose not for its direct antiviral effect, but to inhibit the metabolism of Darunavir, 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
High Barrier to Resistance: The boosted Darunavir regimen is known for its very high genetic barrier to resistance. It is highly effective against multidrug-resistant HIV strains that have failed to respond to other protease inhibitors.
Potent Viral Suppression: The combination provides potent and durable viral suppression, effectively reducing the HIV viral load to undetectable levels and improving the patient’s immune function.
Effective for Treatment-Experienced Patients: This specific dosing regimen is a preferred choice for patients who have failed previous antiretroviral regimens due to its proven efficacy against resistant virus strains.
Flexibility in Dosing: While the standard regimen is twice daily for treatment-experienced patients, once-daily dosing may be an option for treatment-naïve patients, depending on the specific clinical situation.
Uses
HIV-1 Infection: Indicated for the treatment of HIV-1 infection in adults and adolescents weighing at least 15 kg, in combination with other antiretroviral agents.
Treatment-Experienced Patients: The 600 mg/100 mg twice-daily regimen is specifically indicated for patients who have been previously treated and may have darunavir resistance-associated mutations.
Pregnancy: It is a recommended antiretroviral for use in HIV-positive pregnant women to prevent perinatal transmission, with a twice-daily dosing regimen to ensure adequate drug levels.
Post-Exposure Prophylaxis (PEP): It can be used as a component of PEP regimens to prevent HIV infection following a potential exposure.
Nature
Drug Classes: Darunavir 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 (Darunavir): Darunavir 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 Darunavir, leading to higher and more sustained therapeutic concentrations.
Side Effects: A key characteristic of Darunavir is the potential for severe skin reactions and hepatotoxicity (liver damage), particularly in patients with pre-existing liver conditions.
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 Darunavir 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.
