Page 164 - HIV/AIDS Guidelines

Anti-Tuberculosis/Antiretroviral Drug Toxicities
ARV agents and TB drugs, particularly INH, rifamycin, and pyrazinamide, can cause drug-induced hepatitis.
These first-line TB drugs should be used for treatment of active TB disease, even with coadministration of
other potentially hepatotoxic drugs or when baseline liver disease is present (AIII). Patients receiving
potentially hepatotoxic drugs should be monitored frequently for clinical symptoms and signs of hepatitis and
have laboratory monitoring for hepatotoxicity. Peripheral neuropathy can occur with administration of INH,
didanosine (ddI), or stavudine (d4T) or may be a manifestation of HIV infection. All patients receiving INH
also should receive supplemental pyridoxine to reduce peripheral neuropathy. Patients should be monitored
closely for signs of drug-related toxicities and receive alternative ARVs to ddI or d4T.

Immune Reconstitution Inflammatory Syndrome with Tuberculosis and Antiretroviral
Agents
IRIS occurs in two forms: unmasking and paradoxical. The mechanism of the syndrome is the same for both
forms: restoration of immune competence by administration of ART, resulting in an exuberant host response to
TB bacilli and/or antigens. Unmasking IRIS refers to the initial clinical manifestations of active TB that occurs
soon after ART is started. Paradoxical IRIS refers to the worsening of TB clinical symptoms after ART is started
in patients who are receiving TB treatment. Severity of IRIS ranges from mild to severe to life threatening. IRIS
has been reported in 8% to more than 40% of patients starting ART after TB is diagnosed, although the
incidence depends on the definition of IRIS and the intensity of monitoring. 17-18

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Predictors of IRIS include CD4 count <50 cells/mm ; higher on-ART CD4 counts; high pre-ART and lower
on-ART HIV viral loads; severity of TB disease, especially high pathogen burden; and less than 30-day
interval between initiation of TB and HIV treatments. 19-22 Most IRIS in HIV/TB disease occurs within 3
months of the start of TB treatment. Delaying initiation of ART for 2 to 8 weeks may reduce the incidence
and severity of IRIS. However, this possible advantage of delayed ART must be weighed against the
potential benefit of earlier ART in improving immune function and preventing progression of HIV disease
and mortality.

Patients with mild or moderately severe IRIS can be managed symptomatically or treated with nonsteroidal
anti-inflammatory agents. Patients with more severe IRIS can be treated successfully with corticosteroids. A
recent randomized, placebo-controlled trial demonstrated benefit of corticosteroids in the management of
IRIS symptoms (as measured by decreasing days of hospitalization and Karnofsky performance score)
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without adverse consequences. In the presence of IRIS, neither TB therapy nor ART should be stopped
because both therapies are necessary for the long-term health of the patient (AIII).

Immune Reconstitution with Antiretroviral Therapy: Conversion to Positive Tuberculin
Skin Test and Interferon-Gamma Release Assay
Immune reconstitution with ART may result in unmasking LTBI (i.e., conversion of a previously negative
tuberculin skin test [TST] to a positive TST or a positive interferon-gamma [IFN-γ] release assay [IGRA] for
Mycobacterium tuberculosis-specific proteins). A positive IGRA, similar to a positive TST, is indicative of
LTBI in the absence of evidence of active TB disease. Because treatment for LTBI is indicated in the absence
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of evidence of active TB disease, clinicians should be aware of this phenomenon. Patients with a negative TST
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or IGRA and advanced HIV disease (i.e., CD4 count <200 cells/mm ) should have a repeat TST or IGRA after
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initiation of ART and CD4 count increase to >200 cells/mm (BII). 25

Guidelines for the Use of Antiretroviral Agents in HIV-1-Infected Adults and Adolescents J-16

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