Background:
Disseminated Mycobacterium avium complex (MAC) infection remains a serious opportunistic infection in patients with advanced HIV infection, particularly among those with severe immunosuppression. Despite the widespread use of antiretroviral therapy (ART), disseminated MAC (DMAC) continues to be associated with significant morbidity and mortality. The current standard treatment consists of a macrolide-based triple regimen, including a macrolide, ethambutol, and rifamycin. However, in patients with high mycobacterial burden or profound immunodeficiency, early microbiological response and clinical improvement are often suboptimal, and treatment is complicated by drug interactions and tolerability issues.
Objective:
This study aims to evaluate whether adding a fluoroquinolone (levofloxacin or moxifloxacin) to the standard triple therapy improves early clinical outcomes in HIV-infected patients with disseminated MAC infection.
Methods:
This is a prospective, multicenter, randomized, open-label, controlled trial. A total of 124 adult HIV-infected patients with confirmed disseminated MAC infection will be randomly assigned in a 1:1 ratio to receive either standard triple therapy (macrolide, ethambutol, and rifamycin) or an intensified four-drug regimen with the addition of a fluoroquinolone during the initial 8-week intensive phase. Participants will be followed for at least 24 weeks.
Outcomes:
The primary endpoint is the clinical symptom resolution rate at Day 28. Secondary endpoints include microbiological outcomes (culture or molecular conversion at Days 28, 56, and 84), time to culture conversion, mortality, relapse, and safety outcomes including adverse events and QT interval prolongation.
Significance:
This study will provide prospective evidence on whether an intensified treatment strategy can improve early clinical response and microbiological clearance in disseminated MAC infection, while maintaining an acceptable safety profile. The findings may help optimize treatment strategies for HIV-associated disseminated MAC infection.
Age ≥18 years
HIV infection confirmed
Disseminated Mycobacterium avium complex (MAC) infection confirmed by positive culture from a sterile site or positive molecular/sequencing-based detection from a sterile site specimen considered clinically significant
Systemic manifestations consistent with disseminated infection
Prior effective antimycobacterial treatment for >14 days before enrollment
Known macrolide resistance, if susceptibility data are available
Hypersensitivity to macrolides, ethambutol, rifamycins, or fluoroquinolones
Baseline QTc >500 ms or history of significant cardiac arrhythmia
Parallel
Standard Triple Therapy
DrugStandard triple therapy for disseminated MAC infection consisting of a macrolide, ethambutol, and rifabutin, administered according to protocol-defined dosing and duration.
Experimental: Standard Triple Therapy Plus Fluoroquinolone
DrugParticipants receive standard therapy for disseminated Mycobacterium avium complex infection plus a fluoroquinolone during the initial 8-week intensive phase.
Clinical Symptom Resolution Rate at Day 28
The proportion of participants achieving clinical symptom resolution at Day 28. Clinical symptom resolution is defined as meeting all of the following criteria: 1. absence of fever for at least 48 hours without the use of antipyretics; 2. improvement in systemic symptoms, defined as a ≥50% reduction in total symptom score or all individual symptom scores ≤1; 3. stabilization or increase in body weight compared with baseline; 4. no requirement for escalation or modification of antimycobacterial therapy due to disease progression; 5. survival through Day 28. Participants who do not meet all criteria, require rescue therapy, or die before Day 28 are classified as non-responders.
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