Is there evidence for using moxifloxacin (Moxifloxacin) regimens instead of ethambutol (Ethambutol) for treating tuberculosis in people living with Human Immunodeficiency Virus (HIV)?

Moxifloxacin as a Substitute for Ethambutol in Tuberculosis Treatment for People Living with HIV

Moxifloxacin can be used as part of a shorter MDR-TB regimen that includes moxifloxacin instead of ethambutol, particularly in patients with drug-resistant tuberculosis, but it is not recommended as a routine substitute for ethambutol in first-line treatment of drug-susceptible TB in people living with HIV.

Evidence for Moxifloxacin in TB Treatment

MDR-TB Treatment

• The WHO-recommended shorter MDR-TB regimen includes moxifloxacin as a core component: 4–6 Km-Mfx-Pto-Cfz-Z-H(high−dose)-E/5 Mfx-Cfz-Z-E 1
• Moxifloxacin is classified in Group A (fluoroquinolones) of the WHO classification for anti-TB drugs, indicating its importance in MDR-TB treatment regimens 1
• For patients with rifampicin-resistant TB or MDR-TB, a shorter 9–11 month regimen containing moxifloxacin may be used when resistance to fluoroquinolones and second-line injectable agents has been excluded 1

HIV-Specific Evidence

• A recent study (S31/A5349) demonstrated that a 4-month daily regimen substituting rifapentine for rifampin and moxifloxacin for ethambutol had noninferior efficacy and was safe for treating drug-susceptible pulmonary TB in people with HIV with CD4+ counts ≥100 cells/μL on efavirenz-based ART 2
• This 4-month rifapentine-moxifloxacin regimen showed fewer adverse events (15%) compared to the standard 6-month control regimen (21%) in people with HIV 2

Limitations and Considerations

Drug Resistance Concerns

• Using moxifloxacin routinely instead of ethambutol in first-line regimens could lead to increased fluoroquinolone resistance, which would limit future treatment options for MDR-TB 1
• Fluoroquinolones like moxifloxacin are critical drugs for MDR-TB treatment, and preserving their effectiveness is essential 1

Drug Interactions and Dosing

• When moxifloxacin is combined with rifamycins (like rifampicin), plasma concentrations of moxifloxacin can be reduced by up to 31%, which may affect treatment outcomes 3
• Moxifloxacin exhibits extensive interindividual pharmacokinetic variability, which may necessitate therapeutic drug monitoring in some cases 3

Special Situations

• Moxifloxacin may be considered in HIV patients with contraindications or intolerance to rifamycins 4
• For isoniazid-resistant TB, adding a later-generation fluoroquinolone like moxifloxacin to a regimen of rifampin, ethambutol, and pyrazinamide is suggested 1

Practical Recommendations

When to Consider Moxifloxacin Instead of Ethambutol

1. MDR-TB treatment: As part of WHO-recommended shorter regimen 1
2. Rifampicin-resistant TB: When resistance to fluoroquinolones has been excluded 1
3. Intolerance to ethambutol: When patients cannot tolerate ethambutol due to adverse effects 1
4. Isoniazid-resistant TB: As an addition to rifampin, ethambutol, and pyrazinamide 1

Monitoring Requirements

• Regular clinical assessment for treatment response and adverse effects
• Baseline and follow-up visual testing if ethambutol is used
• ECG monitoring may be necessary with moxifloxacin due to QT interval prolongation, especially if patients have baseline QTc > 500 milliseconds or take other QT-prolonging drugs 5

Conclusion

While there is evidence supporting the use of moxifloxacin in specific TB treatment regimens for people living with HIV, particularly in MDR-TB and in the 4-month rifapentine-moxifloxacin regimen, routine substitution of ethambutol with moxifloxacin in first-line treatment of drug-susceptible TB is not currently recommended. The decision to use moxifloxacin should be based on drug susceptibility testing, patient tolerance, and the specific clinical scenario, with consideration of preserving fluoroquinolones for MDR-TB treatment when possible.