What is the appropriate dosing of azithromycin (Azithromycin) for an HIV-positive patient not on antiviral medication, being treated with Augmentin (Amoxicillin-Clavulanate)?

Azithromycin Dosing for HIV-Positive Patients Not on Antiretroviral Therapy

For an HIV-positive patient not on antiretroviral therapy who is also receiving Augmentin, azithromycin should be dosed at 500 mg orally daily when treating MAC infection, or 1,200 mg orally weekly when used for MAC prophylaxis. 1

Azithromycin Dosing Based on Clinical Scenario

For Treatment of Mycobacterium Avium Complex (MAC)

• Treatment of active MAC disease: Azithromycin 500 mg orally daily, combined with ethambutol 15 mg/kg orally daily 1
• This regimen is preferred over clarithromycin in patients receiving certain antiretrovirals due to fewer drug interactions 1
• Consider adding rifabutin 300 mg daily as a third drug for patients with advanced immunosuppression (CD4+ count <50 cells/μL) 1

For MAC Prophylaxis

• Primary prophylaxis: Azithromycin 1,200 mg orally once weekly 1, 2
• This dosing is more effective than daily rifabutin for preventing MAC infection 2, 3
• Weekly dosing is possible due to azithromycin's long half-life and concentration in macrophages 2

For Other Bacterial Infections

• Respiratory infections: Azithromycin 500 mg orally on day 1, followed by 250 mg daily for 4 days 4
• Acute bacterial sinusitis: Azithromycin 500 mg orally daily for 3 days 4
• Pharyngitis/Tonsillitis: 12 mg/kg once daily for 5 days (pediatric dosing) 4

Important Considerations for HIV-Positive Patients

Drug Interactions

• Azithromycin has fewer drug interactions than clarithromycin when combined with antiretrovirals 1
• Azithromycin metabolism is not affected by the cytochrome P450 (CYP450) system, making it safer to use with protease inhibitors or NNRTIs 1
• When using Augmentin (amoxicillin-clavulanate) concurrently, no dose adjustments are needed for either medication 5

Adverse Effects

• Most common side effects include gastrointestinal symptoms: diarrhea (6%), vomiting (6%), and abdominal pain (3%) 4
• Gastrointestinal adverse effects occur in approximately 18% of patients on azithromycin 4
• Serious adverse effects are rare but may include QT prolongation and hepatotoxicity 4

Monitoring

• For MAC treatment, repeat blood cultures should be obtained 4-8 weeks after initiating therapy only if clinical response is inadequate 1
• Clinical improvement (reduced fever, decreased mycobacteremia) typically occurs within 2-4 weeks of appropriate therapy 1
• Monitor for drug resistance if treatment failure occurs (absence of clinical response and persistent mycobacteremia after 4-8 weeks) 1

Special Considerations

Prophylaxis Discontinuation

• MAC prophylaxis may be discontinued if CD4+ count increases to >100 cells/μL for at least 3 months in response to antiretroviral therapy 6
• No episodes of MAC disease were observed in patients with CD4+ counts >100 cells/μL who discontinued prophylaxis 6

Treatment Duration

• Treatment for MAC should be considered lifelong in patients not on antiretroviral therapy 1
• If the patient starts antiretroviral therapy and achieves immune reconstitution (CD4+ >100 cells/μL for at least 12 months), MAC treatment may be discontinued 1

Caution

• Doses of clarithromycin >1 g/day have been associated with increased mortality in HIV patients with MAC and should not be used; this caution should be considered when selecting azithromycin doses as well 1