Enhanced Treatment Strategy for Disseminated MAC Infection in HIV Patients: A Randomized Controlled Trial

May 8, 2026 updated by: Li Liu, Shanghai Public Health Clinical Center

A Multicenter, Randomized, Controlled Trial Evaluating the Efficacy and Safety of Adding Fluoroquinolone (Levofloxacin or Moxifloxacin) to Standard Triple Therapy in Disseminated Mycobacterium Avium Complex Infection

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.

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

Detailed Description

Background and Rationale:

Disseminated Mycobacterium avium complex (MAC) infection remains a major opportunistic infection in patients with advanced HIV infection, particularly among those with severe immunosuppression (e.g., CD4 <50 cells/μL). Although the incidence of disseminated MAC (DMAC) has declined in the era of antiretroviral therapy (ART), it continues to pose a substantial clinical burden due to delayed diagnosis, high mycobacterial load, and frequent co-infections. Clinically, DMAC often presents with systemic symptoms such as fever, weight loss, anemia, and multi-organ involvement, including bone marrow, liver, spleen, and lymph nodes.

Current guidelines recommend a macrolide-based triple therapy consisting of a macrolide (azithromycin or clarithromycin), ethambutol, and a rifamycin (typically rifabutin). This regimen has demonstrated efficacy in reducing mortality and preventing macrolide resistance. However, in real-world clinical practice, early microbiological clearance and symptom improvement remain suboptimal, particularly in patients with high disease burden or delayed immune reconstitution. In addition, drug-drug interactions, especially with ART, and tolerability issues may limit treatment effectiveness.

Fluoroquinolones have demonstrated in vitro activity against mycobacteria and possess favorable pharmacokinetic properties, including good tissue penetration. Retrospective studies suggest that the addition of a fluoroquinolone to standard regimens may improve outcomes in disseminated MAC infection, but high-quality prospective evidence is lacking. Therefore, an intensified treatment strategy incorporating a fluoroquinolone during the early phase of therapy may enhance bacterial clearance and improve clinical outcomes.

Study Objectives:

The primary objective of this study is to determine whether adding a fluoroquinolone (levofloxacin or moxifloxacin) to standard triple therapy improves clinical symptom resolution at Day 28 in HIV-infected patients with disseminated MAC infection.

Secondary objectives include evaluating microbiological outcomes (culture or molecular conversion), time to culture conversion, mortality, relapse, treatment failure, and safety outcomes, including adverse events and QT interval prolongation.

Study Design:

This is a prospective, multicenter, randomized, open-label, controlled clinical trial. A total of 124 eligible adult participants with confirmed disseminated MAC infection will be enrolled and randomized in a 1:1 ratio to one of two treatment arms.

Control group: Standard triple therapy consisting of a macrolide (azithromycin or clarithromycin), ethambutol, and rifabutin (or an equivalent rifamycin-based regimen according to local practice).

Experimental group: Standard triple therapy plus a fluoroquinolone (levofloxacin or moxifloxacin), administered during the initial 8-week intensive phase.

The choice of fluoroquinolone will be determined at baseline based on clinical considerations such as renal function and risk of QT interval prolongation, and will remain fixed during the intensive phase unless safety concerns necessitate modification.

Treatment and Follow-up:

Participants will receive study treatment according to group assignment, with ART initiated or continued as per standard clinical practice, typically within 2 weeks after starting anti-MAC therapy. Patients will be followed for at least 24 weeks, with scheduled visits at baseline and predefined time points (e.g., Days 7, 14, 28, 56, and 84, and Weeks 24 and beyond).

Clinical assessments will include symptom evaluation, physical examination, laboratory tests, and safety monitoring. Microbiological assessments will include culture and/or molecular testing from blood or other sterile sites, with emphasis on consistent sampling sources across time points.

Outcome Measures:

The primary endpoint is the proportion of participants achieving clinical symptom resolution at Day 28, defined by sustained defervescence, improvement in symptom scores, stabilization or gain in body weight, absence of treatment escalation, and survival.

Secondary endpoints include:

Microbiological conversion rates at Days 28, 56, and 84 Time to culture conversion All-cause and MAC-related mortality Relapse and treatment failure rates Safety outcomes, including adverse events (graded by CTCAE), serious adverse events, and QT interval changes

Safety Considerations:

Fluoroquinolones are associated with potential adverse effects, including QT interval prolongation, tendon disorders, and central nervous system toxicity. Therefore, baseline and periodic electrocardiogram monitoring will be performed, along with electrolyte assessment and careful evaluation of concomitant medications. Predefined criteria for dose adjustment or discontinuation will be applied to ensure participant safety.

Significance:

This study aims to generate high-quality prospective evidence on whether an intensified four-drug regimen can improve early clinical and microbiological outcomes in disseminated MAC infection without compromising safety. The results may inform future treatment guidelines and optimize management strategies for HIV-associated disseminated MAC infection.

Study Type

Interventional

Enrollment (Estimated)

124

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • 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
  • Planned initiation of standard antimycobacterial therapy
  • Able and willing to provide written informed consent

Exclusion Criteria:

  • 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
  • Uncorrected hypokalemia or hypomagnesemia
  • History of severe adverse reaction to fluoroquinolones, such as tendon rupture or severe neuropathy
  • Severe hepatic impairment or severe renal dysfunction precluding study treatment
  • Concomitant medications that significantly prolong QT interval and cannot be safely discontinued
  • Pregnancy or breastfeeding
  • Coexisting infection requiring non-protocol antimycobacterial therapy, such as active tuberculosis
  • Any condition that, in the investigator's judgment, would interfere with study participation or interpretation of results

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Standard Triple Therapy
Participants receive standard triple therapy for disseminated Mycobacterium avium complex infection, consisting of a macrolide (azithromycin or clarithromycin), ethambutol, and rifabutin. Antiretroviral therapy is continued or initiated according to standard clinical practice and drug-drug interaction assessment.
Drug: Standard Triple Therapy
Standard triple therapy for disseminated MAC infection consisting of a macrolide, ethambutol, and rifabutin, administered according to protocol-defined dosing and duration.
Other Names:
  • Ethambutol
  • Clarithromycin
  • Azithromycin
  • Rifabutin
Experimental: Standard Triple Therapy Plus Fluoroquinolone
Participants receive standard triple therapy for disseminated Mycobacterium avium complex infection, consisting of a macrolide (azithromycin or clarithromycin), ethambutol, and rifabutin, plus a fluoroquinolone (levofloxacin or moxifloxacin) during the initial 8-week intensive phase. The fluoroquinolone is selected at baseline based on clinical considerations and is intended to remain unchanged during the intensive phase unless modification is required for safety reasons. Antiretroviral therapy is continued or initiated according to standard clinical practice and drug-drug interaction assessment.
Drug: Experimental: Standard Triple Therapy Plus Fluoroquinolone
Participants receive standard therapy for disseminated Mycobacterium avium complex infection plus a fluoroquinolone during the initial 8-week intensive phase.
Other Names:
  • Ethambutol
  • Levofloxacin
  • Moxifloxacin
  • Azithromycin
  • clarithromycin
  • Rifabutin

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Clinical Symptom Resolution Rate at Day 28
Time Frame: Day 28 (±3 days)

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.
Day 28 (±3 days)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Shanghai Public Health Clinical Center

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

April 30, 2026

Primary Completion (Estimated)

December 31, 2028

Study Completion (Estimated)

December 31, 2028

Study Registration Dates

First Submitted

April 14, 2026

First Submitted That Met QC Criteria

May 8, 2026

First Posted (Actual)

May 13, 2026

Study Record Updates

Last Update Posted (Actual)

May 13, 2026

Last Update Submitted That Met QC Criteria

May 8, 2026

Last Verified

April 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • DMAC-RCT-2026

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

Individual participant data that underlie the results reported in this article, after de-identification (text, tables, figures, and appendices), will be shared.

IPD Sharing Time Frame

Beginning 6 months and ending 5 years following article publication.

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL
  • SAP
  • ICF
  • CSR

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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