Page 94 - AIDSBK23C

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The incidence of tuberculosis among persons infected with HIV in the U.S. is increased
when the CD4 lymphocyte count is less than 200/µL. Persons already tuberculin (PPD) positive
at first testing during the course of HIV infection are much less likely to get tuberculosis than
HIV-infected persons who convert to a positive PPD. HIV infection is the greatest known risk
factor for progression from latent tuberculosis to active tuberculosis. In the U.S., after
tuberculosis exposure and infection, HIV-infected persons who do not receive appropriate
treatment progress to active tuberculosis over 5 years at a rate 10 times greater than that for
persons not infected with HIV. HIV-infected persons who have negativity to mumps antigen by
skin testing also have an increased risk for tuberculosis.[430]
Worldwide, prevalence of tuberculosis with HIV parallels prevalence of HIV and lack of
health care resources. In 2008, there were 9.4 million new cases of TB and 1.78 million deaths
from TB worldwide; of these, 1.4 million cases (15%) occurred in HIV-infected individuals,
resulting in 0.5 million deaths (28% of total deaths from TB). Africa, and Southern Africa in
particular, and Southeast Asia, particularly India, have the highest prevalence.[431]
The incidence of MTB as well as the number of deaths from MTB began increasing in
the United States in the mid-1980's, in part due to the AIDS epidemic, but leveled off and
decreased in the 1990's.[428,429] Accompanying this increase in MTB was the emergence in
the 1990's of MTB strains exhibiting multiple drug resistance. Emergence of multidrug-resistant
TB (MDR TB) may be a function of inadequate control: poor surveillance, delayed diagnosis,
inappropriate drug taking by patients, or inappropriate drug prescribing by physicians.[432] The
clinical presentation is similar to non-resistant strains, though the chest roentgenographic
appearance is more often an alveolar infiltrate, and cavitation is more frequent than with non-
resistant MTB. These resistant strains are also likely to result in pathologic lesions with poor
granuloma formation, extensive necrosis, neutrophilic inflammation, and numerous acid-fast
bacilli.[433] There is a higher fatality rate in persons with HIV infection. The Beijing genotype
family of M tuberculosis organisms is associated with the greatest drug resistance.[434]
Active MTB infection in patients with AIDS probably results from reactivation of
previous infection rather than primary infection. The incidence of clinically apparent MTB
infection is highest in HIV-infected persons in the first months after beginning antiretroviral
therapy, probably from immune restoration that unmasks a subclinical inflammatory response.
Despite immunosuppression, pulmonary involvement by MTB in AIDS is still far more common
than extrapulmonary spread. Not all AIDS patients have reactivation of prior MTB infection,
because isolated fibrotic or calcified granulomas without evidence for active granulomatous
disease can be found in some AIDS cases at autopsy.[435] Persons with HIV can have latent
MTB infection, and the rate of progression to active tuberculosis disease is estimated to be 5 to
8% per year, compared with a 10% lifetime risk in the general population. HIV is also associated
with higher rates of extrapulmonary and disseminated MTB.[431]
The risk for developing active MTB infection is greatest in the first 90 days following
initiation of antiretroviral therapy. The incidence of MTB is highest for persons with greater
immunosuppression upon starting antiretroviral therapy, particularly with CD4 lymphocyte
counts below 50/µL. Additional risk factors include anemia and poor nutritional status.[434]
MTB infection may be more likely to occur in association with HIV infection through
alterations in alveolar macrophage function. The macrophages in asymptomatic HIV-infected
persons show increased phagocytosis of mycobacteria along with decreased release of cytokines
and chemokines, and impaired phagosome maturation. There is also decreased apoptosis of
alveolar macrophage in response to mycobateria, reducing clearance of the organisms. Lung