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infections from disseminated Mycobacterium avium complex (MAC) infections include night
sweats, extra-inguinal lymphadenopathy, acid fast bacilli in sputum smears, hilar enlargement on
chest radiograph, miliary lesions, and pleural effusions. Hepatosplenomegaly, elevated serum
alkaline phosphatase (twice normal), and leukopenia are more likely to suggest disseminated
MAC.[440]
Grossly, MTB produces recognizable discrete tan to white, firm granulomas in most
involved organs. Unlike MAC, the lesions will not show bright yellow coloration. Most of the
granulomas are 0.1 to 0.5 cm, but larger granulomas can occur and demonstrate central
caseation. Large cavitary lesions with AIDS are not common. A classic miliary pattern is not
seen frequently because the granulomas of MTB in AIDS tend to be more variably sized and
more widely scattered in distribution. A pneumonic pattern may occasionally be seen.
The microscopic appearance of MTB with AIDS can be typical of that seen in MTB
infecting non-AIDS patients. The granulomas contain epithelioid cells, Langhans giant cells,
lymphocytes, and fibroblasts with central caseation. In many cases, the inflammatory response is
poor and the granulomas are ill defined, particularly in advanced AIDS. Acid-fast stains show
variable numbers of mycobacteria, but usually there are more mycobacteria than are seen in non-
AIDS patients. In some cases with few or small granulomas, mycobacteria are not numerous; in
other cases with many larger caseating granulomas, they may be abundant. Large macrophages
filled with mycobacteria similar to those seen in MAC are quite uncommon in MTB.[441]
Persons on active MTB therapy starting antiretroviral therapy (ART) can develop
immune restoration inflammatory syndrome (IRIS) with a vigorous delayed-type
hypersensitivity reaction and more pronounced granulomatous inflammation from mycobacterial
infection. There may be thoracic lymphadenitis in addition to active pulmonary disease.
Extrathoracic disease, however, is unlikely to occur with IRD.[285] Risk factors for IRIS are
disseminated MTB, low CD4 count and shorter interval from start of MTB therapy to beginning
antiretroviral therapy. IRIS with MTB typically last 2 to 3 months.[442]
Persons with HIV infection and MTB are more likely to develop adverse antitubercular
drug reactions and antitubercular drug resistance. Death from MTB is more common than with
MAC from both an increase in the numbers of infections and death rate from infection. The rise
in multiple drug resistant (MDR) strains of MTB has played a role in this increasing death
rate.[428,433,442] Worldwide, about 5% of tuberculosis cases are MDR and it is likely half of
those occur in HIV-infected persons. The incidence of tuberculosis declines with the use of
antiretroviral therapy.[431]
Treatment of mycobacterial illness in conjunction with HIV infection may require special
consideration for use of drugs. Drug interactions between antiretrovirals and antituberculars are
common because of induction or inhibition of hepatic enzymes cytochrome P450 (CYP450). The
isoform CYP3A4 is primarily responsible for the metabolism of protease inhibitors (PI) and non-
nucleoside reverse transcriptase inhibitor (NNRTI). Rifampicin is a potent inducer of
CYP3A4.[442]
In general, for untreated patients, MTB therapy is initiated first. If both illnesses are
treated simultaneously, then recommended regimens include use of the antiretroviral efafirenz
with 2 nucleoside reverse transcriptase inhibitors plus 4 MTB drugs (isoniazid, rifampin,
ethambutol, pyrazinamide) or a ritonavir-boosted protease inhibitor with 2 nucleoside reverse
transcriptase inhibitors along with the MTB drugs (but rifabutin is substituted for rifampin). For
atypical mycobacterial infection with HIV, the antimycobacterials employed along with
antiretrovirals are rifabutin, clarithromycin, and ethambutol.[282]