I. Is prophylaxis for Mycobacterium avium complex (MAC), with either clarithromycin, azithromycin, or rifabutin, indicated in children with HIV infection who have advanced immunosuppression to prevent MAC infection?
- Prophylaxis with either clarithromycin or azithromycin should be offered to children with HIV infection who have advanced immunosuppression (strong, low)
- Children aged <1 year: <750 cells/mm3
- Children aged 1 to <2 years: <500 cells/mm3
- Children aged 2 to <6 years: <75 cells/mm3
- Children aged ≥6 years: <50 cells/mm3
- For children who cannot tolerate azithromycin or clarithromycin, rifabutin is an alternative prophylactic agent for MAC, although drug interactions and lack of efficacy data in children limit its use (weak, very low).
II. In children with HIV infection aged ≥2 years on stable antiretroviral therapy (ART) for ≥6 months and experiencing sustained (>3 months) CD4 T lymphocyte (CD4) cell count recovery, is discontinuation of primary prophylaxis associated with risk of disseminated MAC infection?
- Primary prophylaxis can be discontinued in children with HIV infection aged ≥2 years receiving stable antiretroviral therapy (ART) for ≥6 months and experiencing sustained (>3 months) CD4 count recovery well above the age-specific target for initiation of prophylaxis (i.e., as in adults, >100 cells/mm3 for children aged ≥6 years [strong, high]; and >200 cells/mm3 for children aged 2 to <6 years [strong, moderate]).
III. In children with HIV infection and MAC disease, is testing MAC isolates for susceptibility indicated to guide management?
- Testing of MAC isolates for susceptibility to clarithromycin or azithromycin is recommended (strong, very low).
IV. In children with HIV infection and MAC disease, does combination therapy with a minimum of 2 drugs compared with monotherapy prevent or delay the emergence of resistance?
- Combination therapy with a minimum of 2 drugs (e.g., clarithromycin or azithromycin plus ethambutol) is recommended to prevent or delay the emergence of resistance (strong, moderate). Monotherapy is associated with the emergence of high-level drug resistance.
V. In children with HIV infection and MAC disease, does the use of clarithromycin (as compared to azithromycin) improve clearance of bacteremia?
- There are insufficient data to recommend the use of clarithromycin over azithromycin. Some experts use clarithromycin as the preferred first agent, reserving azithromycin for patients with substantial intolerance to clarithromycin or when drug interactions with clarithromycin are a concern. (strong, low)
VI. In children with HIV infection and MAC disease who are treated with combination therapy, does the addition of a third agent provide improved clearance of infection?
- Use of rifabutin as a third drug added to the macrolide/ethambutol regimen is controversial (weak, very low). Some experts would add rifabutin as a third drug to the clarithromycin/ethambutol regimen, particularly in the absence of ART and in the presence of high mycobacterial counts; however, with such combination therapy, drug interactions should be checked carefully, and more intensive toxicity monitoring may be warranted (strong, very low). Other experts recommend against using this third agent in children because of rifabutin’s increased cytochrome P450 activity, which leads to increased clearance of other drugs such as protease inhibitors and non-nucleoside reverse transcriptase inhibitors, and the potential for increased toxicity associated with concomitant administration of drugs.
VII. In patients with HIV infection and MAC infection who are antiretroviral naive, what is the optimal timing to start ART to prevent IRIS?
- In patients with HIV and disseminated MAC disease who have not been previously ART treated, or are not receiving effective ART initiation, ART generally should be withheld until after the first 2 weeks of antimycobacterial therapy have been completed to reduce the risk of drug interactions and complications associated with IRIS and to lower the pill burden (weak, very low).
VIII. In patients with HIV infection and MAC infection who have failed treatment (defined as the absence of clinical response and the persistence of mycobacteremia after 8 to 12 weeks of treatment) is there an indication to repeat susceptibility testing to help guide clinical management?
- Treatment failure is defined as the absence of clinical response and the persistence of mycobacteremia after 8 to 12 weeks of treatment. Repeat susceptibility testing of MAC isolates is recommended in this situation, and a new multidrug regimen of two or more drugs not previously used, and to which the isolate is susceptible, should be administered (strong, very low). Drugs that should be considered for this scenario include rifabutin, amikacin, and a quinolone.
IX. In children with HIV infection with disseminated MAC and continued immunosuppression, does secondary prophylaxis prevent recurrence of infection?
- Children with a history of disseminated MAC and continued immunosuppression should receive lifelong prophylaxis to prevent recurrence (strong, low). Secondary prophylaxis typically consists of continued multidrug therapy used in treatment of disease.
X. In children with HIV infection with disseminated MAC and sustained CD4 recovery, is discontinuation of secondary prophylaxis associated with risk of relapse?
- Some experts recommend discontinuation of therapy in children with HIV infection who meet all of the following criteria:
- Aged ≥2 years and have completed ≥12 months of treatment for MAC;
- Remain asymptomatic for MAC;
- Receiving stable ART (i.e., ART not requiring change for virologic or immunologic failure);
- Have sustained (≥6 months) CD4 count recovery well above the age-specific target for initiation of primary prophylaxis (i.e., as in adults, >100 cells/mm3 for children aged ≥ 6 years [strong, low] and >200 cells/mm3 for children aged 2 to <6 years [weak, very low]).