Download Mycobacterium avium Complex and HIV Demetre C. Daskalakis

MYCOBACTERIUM AVIUM COMPLEX AND HIV
Demetre C. Daskalakis, M.D.
October 29, 2002
Introduction
Mycobacterium avium complex refers two the two non-tubeculous mycobacteria M. intracellulare and M.
avium. MAC disease occurs in HIV negative patients, but epidemiologically, it is more of a concern in the
HIV infected population. Patients with CD4 counts less than 50cell/mm 3 are at increased risk for
disseminated disease. 15-40% of patients with advanced HIV are thought to harbor MAC infection.
Pathogenesis
 Bacterial factors: These are not well defined, since MAC tends not to be considered a particularly
virulent organism. Mycobacteria with plasmids or transparent colony morphology are associated
with increased virulence. One study also demonstrated increased replication of isolates from HIV
patients when compared to environmental isolates. It is unclear why this is.
 Route of Acquisition: Not person to person. Felt to be environmental. The majority of patients
get MAC through ingestion; pulmonary acquisition is also possible. It is unproven if MAC
infection can reactivate like TB. It is felt that most cases of disseminated MAC represent new
infections from the following lines of evidence:
o Rate of disseminated MAC infection in HIV greater than one would expect based on
prevalence of MAC + DTH reactions in the general population
o Disease can be detected locally in most cases prior to dissemination
o MAC antibodies absent in AIDS patients with disseminated disease
 Adherence and Invasion: Mycobacteria through unknown adherence receptors attach to the
intestinal epithelium and penetrate the mucosa though unclear mechanisms of invasion. These
organisms then undergo phagocytosis by macrophages. The macrophages of HIV infected
patients are unable to mediate intracellular killing, and the macrophages become MAC factories.
This defect is felt to be secondary to cytokine defects since these MAC-laden macrophages can
be activated with cytokines in vitro. The macrophages rupture releasing MAC bacilli leading to
local foci of sheets of MAC-laden macrophages most commonly in the duodenum but visible as 24 mm punctate lesions through out the gut. Infection spreads to lymphatics, reticuloendothelial
organs, the bone marrow and to the blood.
 Other: The macrophages infected with MAC also become HIV factories, producing more virus.
This complex interaction is felt to explain why patients with MAC seem more
immunocompromised than similar patients without MAC and are prone to other OI’s leading to
increased mortality rates.
Clinical Manifestations
 Disseminated Disease: Non-specific. These include fever, abdominal pain, night sweats,
diarrhea, and weight loss. Anemia is common and may be caused by bone marrow infiltration or
other “unclear” mechanisms that resemble anemia of chronic disease. Elevated alkaline
phosphotase of hepatic origin and LDH are also frequently seen. Diagnosis is by isolation of
MAC.
 Localized Disease: These focal findings were rarely encountered in the HIV population until the
dawn of HAART. Now focal lymphadenitis (cervical, abdominal, mediastinal) is reported after the
initiation of HAART and is thought to be a part of the spectrum of Immune Reconstitution
Inflammatory Syndrome (IRIS).
Diagnosis
 Blood cultures
 Bone marrow culture and AFB stain
Therapy
 Clarithromycin (500 PO BID)or azithromycin in combination with ethambutol or rifabutin
 In one study, clarithromycin + ethambutol was superior to azithromycin + ethambutol.
 Clarithromycin increases levels of rifabutin and rifabutin decreased levels of clarithromycin while
increasing levels of its metabolites. This combination also had a higher rate of rifabutin uveitis.
Beth Israel Deaconess Medical Center Residents’ Report
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A later study revealed that clarithromycin+ethambutol+rifabutin increased survival compared to
clarithroycin and either ethambutol or rifabutin. Three drug regimens are favored, but rifabutin
should be used cautiously in patients on protease inhibitors.
G-CSF is being studied as adjuvant therapy that may improve macrocyte killing of MAC.
Discontinuation of therapy after immune reconstitution is being studied. For now, therapy is life
long.
Prophylaxis
 All patients with CD4 counts less than 50 cells/mm 3 should be prophlaxed
 Preferred regimens are clarithromycin 500 mg PO BID or azithromycin 1200 mg q week
 Rifabutin is an inferior choice to the macrolides
 If immune reconstitution occurs (CD4 > 100 cells/mm 3 for 3-6 months), MAC prophlyaxis may
safely be discontinued.
Bibilography
Horsburgh, CR. The Pathophysiology of disseminated Mycobacterium avium complex disease in AIDS.
JID. 1999; 179 (Suppl3): S461-5.
Tantisiriwat. W. Prophylaxis of opportunistic infections. Infectious Disease Clinic of North America. 2000:
Vol 14. Number 4.
Beth Israel Deaconess Medical Center Residents’ Report