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Mycobacterium Tuberculosis Infection in the HIV-Infected Patient

Epidemiology of TB and HIV

TB in HIV-infected patients was responsible for much of the increase in U.S. TB cases in the late 1908s

Rapid progression to active disease is well documented, particularly in those patients with CD4 cells below 50 to 100 per mm3

The clinical presentation of TB in HIV-infected patients is often atypical, leading to a failure to

Anergy with tuberculin testing is frequently present

Primary disease does not cause the apical pulmonary involvement

Disseminated and extrapulmonary disease are common

Failure to consider the diagnosis resulted in nosocomial and institutional outbreaks of TB affecting both patients and health care workers

HIV and Multi-drug Resistant Tuberculosis TB

Currently resistance rates for US isolates are:
INH = 8%, Rifampin = 3% (mono-resistance to rifampin higher among HIV-infected), PZA = 3%, EMB = 2%, Streptomycin = 6%, MDR = 2%

38% of cases reported from New York City

MDR TB mortality rate has been very high, up to 90%; prompt initial treatment with at least two active drugs greatly improves outcome

Transmission of TB to health care workers, with several HIV-seropositive health-care workers developing MDR-TB with a fatal outcome

Fortunately, the prevalence and incidence of MDR-TB has fallen with implementation of effective control strategies including adherence to isolation precautions, early initiation of empirical therapy directed against MDR strains, and institution of directly observed therapy: in New York City a 29% reduction in proportion of MDR cases (from 19% to 13%) and 50% reduction in number of patients

Failure of patient to defervesce while receiving standard four-drug therapy may be marker in identifying patients with MDR TB

Pathogenesis, clinical presentation, diagnosis

M. tuberculosis is an obligate aerobic organism that spreads almost exclusively by the respiratory route

MTB enhances HIV replication and transmission to T-cells in vitro and probably in vivo

In HIV disease, the immune system is unable to hold M. tuberculosis in check

Patients with advanced HIV disease are unable to limit the spread and multiplication of M. tuberculosis with early stages of infection, resulting in a primary tuberculous pneumonia and initial dissemination

 HIV-infected patients with dormant, previously contained loci of infection, eventually develop reactivation TB because of the gradual loss of cell-mediated immunity

The clinical presentation of TB in HIV-infected patients varies depending on the severity of immunosuppression

In patients with earlier stages of HIV disease (as indicated by higher numbers of circulating CD4 cell counts of 300 or above), the presentation tends to be like that in persons without immunodeficiency

With CD4 counts of less than 200, the features of TB are often atypical, with a much greater frequency of extrapulmonary involvement and diffuse pulmonary disease without cavitation

Patients with advanced HIV disease more often have miliary TB and involvement of the lymphatic system, central nervous system(parenchymal and meningeal), soft tissue, bone marrow, liver, and other viscera

TB can masquerade as any one of the several other pulmonary infections and lymphadenopathic diseases that are common in HIV-infected, leading to a failure to consider the diagnosis; M. kansasii has a similar presentation and may be on the rise5. Infectivity and smear and culture positivity are no different for HIV-positive versus HIV-negative patients; 1-2 smears and cultures may be sufficient to

Treatment

HIV-positive patients with AFB present in sputum or biopsy specimens or whose cultures yield AFB should be treated for M. tuberculosis (see Table 1 for listing agents useful for

HIV-infected patients with tuberculosis respond well to treatment if the infecting organism is sensitive to INH and rifampin and these agents can be used.

Treatment considerations

Relapse (recurrence rates): 5-9%, probably higher than for HIV-negatives and more likely to occur in those with