Treatment of NTM Infections in HIV-Positive Patients
For HIV-infected patients with disseminated MAC disease, treat with clarithromycin (1,000 mg daily) or azithromycin (250 mg daily) plus ethambutol (15 mg/kg daily) with or without rifabutin (150-350 mg daily), and continue treatment lifelong unless immune restoration is achieved with antiretroviral therapy. 1
Key Epidemiologic Context
Disseminated NTM disease occurs almost exclusively in severely immunocompromised HIV patients with CD4 counts below 50 cells/μL, with MAC accounting for over 90% of cases. 1 Patients with CD4 counts below 10 cells/μL have nearly a 40% risk of developing disseminated MAC within one year without prophylaxis. 1
Treatment Regimen for Disseminated MAC in HIV
Core Antimycobacterial Therapy
- Macrolide backbone: Use clarithromycin 1,000 mg daily OR azithromycin 250 mg daily 1
- Ethambutol: 15 mg/kg daily 1, 2
- Rifabutin (optional): 150-350 mg daily, though drug interactions with antiretroviral therapy are substantial 1
Azithromycin is generally preferred over clarithromycin due to better tolerance, fewer drug interactions, lower pill burden, and once-daily dosing. 2
Critical Drug Dosing Warnings
Never use clarithromycin at doses exceeding 500 mg twice daily (1,000 mg total daily) in HIV patients, as higher doses are associated with excess mortality. 1 When combining clarithromycin with rifabutin, monitor closely for rifabutin toxicity including arthralgias, uveitis, neutropenia, and liver dysfunction, as this combination elevates rifabutin serum levels. 1 Rifabutin also reduces clarithromycin levels, potentially compromising efficacy. 1
Managing Drug-Drug Interactions with Antiretroviral Therapy
Rifabutin induces cytochrome P-450 enzymes and significantly interferes with protease inhibitors and non-nucleoside reverse transcriptase inhibitors. 1 Rifabutin cannot be used with certain antiretroviral agents and requires dose modification with others—consult current CDC guidelines for specific combinations. 1 If severe drug interactions or toxicity occurs, rifabutin should be dose-reduced or discontinued entirely. 1
Treatment Duration and Discontinuation Criteria
When to Stop Treatment
Treatment should be considered lifelong unless immune restoration occurs. 1 MAC treatment may be safely discontinued in patients who meet ALL of the following criteria: 1
- Completed at least 12 months of antimycobacterial therapy
- Remain completely asymptomatic for MAC disease
- Achieved CD4 count >100 cells/μL sustained for at least 6 months on HAART
- No detectable MAC in blood cultures
Restart treatment if CD4 count drops below 100 cells/μL. 1
Treatment of Non-MAC NTM Species in HIV
For M. kansasii and other non-MAC species causing disseminated disease in HIV patients, follow standard treatment guidelines for non-HIV-infected persons but extend treatment duration to at least 6-12 months after immune restoration. 1 M. kansasii responds favorably to standard therapy even in HIV patients. 1
Primary Prophylaxis for MAC
Indications and Regimens
All HIV patients with CD4 counts <50 cells/μL should receive MAC prophylaxis. 1 Before initiating prophylaxis, rule out active disseminated MAC disease with clinical assessment and blood cultures if warranted. 1
Preferred prophylaxis regimen: Azithromycin 1,200 mg once weekly 1, 2
Alternative regimen: Clarithromycin 500 mg twice daily (though higher risk of macrolide-resistant breakthrough compared to weekly azithromycin) 1
Second-line alternative: Rifabutin 300 mg daily (less effective, use only if macrolides cannot be tolerated) 1
Discontinuing Prophylaxis
Stop primary MAC prophylaxis when CD4 count rises above 100 cells/μL for more than 3 months on HAART. 1 Reinitiate prophylaxis if CD4 count falls below 50-100 cells/μL. 1
Pulmonary NTM Disease in HIV Patients
For HIV patients with pulmonary (not disseminated) NTM disease meeting ATS/IDSA diagnostic criteria, treatment approaches mirror those for non-HIV patients but require careful attention to drug interactions with antiretroviral therapy. 3 The complexity of managing concurrent HIV and NTM medications necessitates close monitoring for both drug interactions and overlapping toxicities. 3
Critical Pitfalls to Avoid
Never use macrolide monotherapy for any NTM infection at any time, as this rapidly induces resistance and guarantees treatment failure. 4, 2 This is the single most important error to avoid. 4
Exclude active tuberculosis before starting rifabutin prophylaxis, as rifabutin monotherapy could induce rifampin resistance in undiagnosed TB. 1
Do not routinely screen respiratory or gastrointestinal specimens for MAC in asymptomatic patients with negative blood cultures, as no data support prophylaxis efficacy in this scenario. 1
Monitoring Requirements
Establish baseline and ongoing monitoring for hearing loss, visual changes, renal function, and liver enzymes based on the specific antimycobacterial agents used. 4 Monitor for immune reconstitution inflammatory syndrome (IRIS) when initiating or optimizing antiretroviral therapy in patients with recent or active NTM infection. 5, 6