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CHAPTER 69: Human Immunodeficiency Virus (HIV) and AIDS in the Intensive Care Unit 635

TABLE 69-5 Guidelines for Discontinuation of Primary and Secondary Prophylaxis for Selected Opportunistic Infections Following Antiretroviral-induced Immune Reconstitution 82
Opportunistic Infection Initiate Primary Prophylaxis Discontinue Primary Prophylaxis Discontinue Secondary Prophylaxis
3
Pneumocyctis jirovecii pneumonia • CD4 <200 cells/mm or history of • CD4 >200 cells/mm for ≥3 months • CD4 >200 cells/ mm for ≥3 months
3
3
oropharyngeal candidiasis
3
3
Toxoplasma encephalitis (TE) • Toxoplasma seropositive and CD4 • CD4 >200 cells/mm for ≥3 months • CD4 >200 cells/ mm for ≥6 months, completed initial
<100 cells/ mm 3 therapy and remain free of signs and symptoms of TE
3
Mycobacterium avium complex • CD4 <50 cells/ mm 3 • CD4 >100 cells/ mm for ≥3 months • CD4 >100 cells/ mm for ≥6 months on ART, and 12 months of
3
MAC therapy with documented clinical and microbiologic resolution
Cryptococcus neoformans Not indicated Not applicable • CD4 ≥100 cells/ mm for ≥3 months with suppressed plasma
3
HIV RNA, and asymptomatic for cryptococcal infection, after
completion of initial therapy and 1 year of maintenance
therapy
3
Cytomegalovirus Retinitis Not indicated Not applicable • CD4 >100 cells/mm for ≥6 months with suppressed plasma
HIV RNA. Requires confirmation of clinical resolution of disease
epidemic, mortality was greater than 80% in most series. Mortality Tuberculosis is usually diagnosed with smear and culture of sputum
97
has been reduced to less than 50% with the addition of systemic cortico- or BAL. Of particular note, blood culture may have a diagnostic yield
steroids. 78,87,88 However, if PJP-related acute respiratory failure develops (2%-12% in some patients). Rapid diagnostic tests (within 24 hours)
despite early intervention with maximal therapy, including corticoste- have been approved for the detection of M tuberculosis RNA or DNA
roids and appropriate antimicrobial agents, the prognosis appears to be in respiratory tract specimens. Such tests are particularly useful in the
dismal, with a mortality greater than 90% in some series. 98 management of selected patients who are positive or negative for an
acid-fast bacilli smear, particularly for those with an intermediate pretest
MYCOBACTERIUM TUBERCULOSIS probability of having tuberculosis. 102,103
HIV is associated with significantly increased risk of reactivation ■ MANAGEMENT
of latent tuberculosis and progression to active disease in recently
acquired infections. Tuberculosis occurs with varying degrees of fre- Current therapeutic guidelines (revised recently by the American
quency among HIV-infected individuals, reaching 20% in some series. Thoracic Society [ATS] and the CDC) recommend a standard approach
Tuberculosis is now seen as a major pulmonary infection in HIV-infected to tuberculosis therapy in the setting of HIV infection, that is, first-line
positive patients in many resource-limited settings. Because the risk therapy with quadruple-drug regimens initially for the first 2 months
99
of developing tuberculosis is proportional to the risk of developing consisting of isoniazid (plus pyridoxine), rifampin, pyrazinamide, and
it prior to the acquisition of HIV, its incidence in North America is ethambutol. The continuation phase of treatment consists of isoniazid
greatest among intravenous drug users, aboriginal populations, and (plus pyridoxine) and rifampin for four more months (total
104,105
individuals originally from TB-endemic regions. Tuberculosis usually 6 months). Patients who respond slowly to treatment should
develops within the year prior to the diagnosis of other AIDS-defining have the continuation phase of treatment increased to 7 months (total
conditions. Either pulmonary or disseminated tuberculosis in an HIV- 9 months, or 6 months after documented culture conversion). During
infected individual is diagnostic of AIDS according to the CDC clas- the continuation phase, treatment may be administered either on a daily
sification of HIV disease. basis or three times weekly. Due to concerns regarding increased risk of
rifampin resistance, the use of daily treatment, as opposed to twice or
■ CLINICAL AND RADIOLOGIC FEATURES three times weekly dosing schedules, is recommended, particularly in
The symptoms of tuberculosis in the context of HIV generally are patients with CD4 cell counts under 100 cells/mm . 3 104,105
A high proportion of patients with multidrug-resistant tuberculosis
nonspecific because “classic” tuberculosis symptoms (fatigue, malaise, (MDR-TB) have been HIV-infected. 106,107 MDR-TB should be suspected
weight loss, fever, and night sweats) are extremely common, even in in patients with persistent fevers after 14 days of therapy, particularly in
moderately advanced stages of HIV disease. In contrast to the immuno- areas of high prevalence. Persistent fevers have also been associated
108
competent host, in the context of HIV disease, reactivating tuberculosis with extensive pulmonary or miliary disease in cases of non-MDR-TB.
usually has radiologic features similar to those of primary tuberculosis, In contrast to previous reports, HIV-infected patients with MDR-TB
including hilar and/or mediastinal adenopathy, middle and lower lung had survival rates similar to those with non-MDR-TB when an early
infiltrates, pleural effusions, or a miliary pattern. Apical infiltrates or diagnosis was established and treatment was initiated with a regimen
cavities are seen only in a minority of patients. As many as 9% of patients containing at least two drugs to which the isolate was susceptible in
with AIDS-related TB with CD4 counts of less than 200 cells/mm have vitro. Expert consultation is recommended for the management of
3
108
a normal chest x-ray with a positive sputum culture for tuberculosis. patients with suspected or proven drug-resistant TB. Principles of ther-
100
Furthermore, PJP is diagnosed simultaneously in as many as 25% of the apy include the use of at least three previously unused drugs, not limiting
cases of tuberculosis. regimens to three drugs if other active unused drugs are available (since
■ DIAGNOSIS four- to six-drug regimens appear to be more effective), using directly
observed therapy (DOT), and avoiding intermittent therapy except pos-
104
Tuberculin skin testing (PPD) with a threshold of 5 mm induration may sibly for injectable drugs after the first 2 to 3 months. MTb-IRIS is
be useful among HIV-infected individuals because tuberculosis devel- important to consider in the differential diagnosis of any HIV-positive
ops more frequently in patients known to have a previously positive test; patient who appears to worsen during the course of therapy for MTb.
however, at the time of diagnosis of AIDS, at least 30% of patients are Drug interactions occur predominantly due to rifampin-related
anergic. Other modalities such as interferon-γ release assays (IGRAs) induction of the cytochrome P-450 isoenzyme 3A4. Concomitant use
may supplement the PPD to diagnose prior tuberculosis exposure and of rifampin leads to reductions in concentrations of the non-nucleoside
thus play a role in evaluating potential risk for active tuberculosis. 101 reverse transcriptase inhibitors. 109,110 This effect is greater for nevirapine,

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