What is the recommended prophylaxis regimen for Mycobacterium Avium Complex (MAC) in patients with Human Immunodeficiency Virus (HIV) and a low CD4+ (Cluster of Differentiation 4+) count?

MAC Prophylaxis in HIV Patients with Low CD4+ Counts

Azithromycin or clarithromycin are the preferred prophylactic agents for Mycobacterium Avium Complex (MAC) in HIV-infected patients with CD4+ counts below 50 cells/μL. 1

Primary Prophylaxis Recommendations

When to Start Prophylaxis

• Initiate MAC prophylaxis in all HIV-infected patients with CD4+ counts <50 cells/μL (AI) 1
• Before starting prophylaxis:
  • Rule out active disseminated MAC disease through clinical assessment
  • Consider obtaining a blood culture for MAC
  • Rule out active tuberculosis (TB) if rifabutin will be used (to prevent rifampin resistance) 1

First-Line Prophylactic Regimens

1. Azithromycin:

   • Dosage: 1200 mg orally once weekly 2
   • Strong evidence supports efficacy (AI) 1

2. Clarithromycin:

   • Dosage: 500 mg orally twice daily 3
   • Strong evidence supports efficacy (AI) 1
   • FDA-approved specifically for MAC prophylaxis 3

Alternative Prophylactic Regimen

• Rifabutin:
  • Consider only if macrolides cannot be tolerated
  • Dosage: Not specified in evidence
  • Moderate evidence supports efficacy (BI) 1
  • Caution: Drug interactions may complicate use 1

Combination Regimens (Not Recommended)

• Clarithromycin + rifabutin: Not more effective than clarithromycin alone and has higher adverse effect rates (EI) 1
• Azithromycin + rifabutin: More effective than azithromycin alone but not routinely recommended due to:
  • Additional cost
  • Increased adverse effects
  • Potential drug interactions
  • No survival difference compared to azithromycin alone (CI) 1

When to Discontinue Prophylaxis

• Discontinue primary MAC prophylaxis when:

  • CD4+ count increases to >100 cells/μL for >3 months in response to antiretroviral therapy (ART) (AI) 1
  • This recommendation is supported by randomized, placebo-controlled trials showing minimal risk of MAC disease after prophylaxis discontinuation 4

• Benefits of discontinuation:

  • Reduced pill burden
  • Decreased drug toxicity risk
  • Fewer drug interactions
  • Reduced risk of drug-resistant pathogens
  • Cost savings 1

• Reinstitute prophylaxis if:

  • CD4+ count decreases to <50 cells/μL (AIII) 1

Special Considerations

Drug Interactions

• Pay particular attention to interactions between MAC prophylactic agents and:
  • Antiretroviral protease inhibitors
  • Non-nucleoside reverse transcriptase inhibitors 1
• Clarithromycin doses >1 g/day are associated with increased mortality and should not be used (EI) 1

Additional Benefits

• Both azithromycin and clarithromycin provide additional protection against respiratory bacterial infections (BII) 1

Monitoring

• Routine screening of respiratory or gastrointestinal specimens for MAC is not recommended (DIII) 1

Impact of HAART/ART on MAC Prophylaxis

• Since the advent of effective ART, MAC infection rates have declined substantially 5
• In the Johns Hopkins cohort, MAC infection rates decreased from 16% pre-1996 to less than 1% per year currently 5
• Some experts suggest that routine MAC prophylaxis may not be necessary for patients who respond well to ART, even with initially low CD4+ counts 6

The evidence clearly supports using either azithromycin or clarithromycin as first-line prophylaxis for MAC in HIV patients with CD4+ counts below 50 cells/μL, with discontinuation once CD4+ counts rise above 100 cells/μL for at least 3 months on effective ART.