IRIS is a frequent early complication of ART in people with HIV and TB. There are two types of IRIS. The first occurs during TB therapy, after ART initiation, and is known as paradoxical IRIS. The second occurs following ART initiation in patients with unrecognized TB, and is known as unmasking IRIS.47,50,51
IRIS has been reported with a frequency ranging from 8 to 43%.52 IRIS usually presents as fever and disease progression at involved sites, for example as enlarging lymph nodes, worsening pulmonary infiltrates on chest radiograph or exacerbation of inflammatory changes at other sites. Mortality attributed to IRIS appears to be uncommon except in cases with CNS involvement. Most affected patients have low initial CD4 cell counts, typically 100 × 106/L or less. Onset has been described between 2 and 40 days after ART initiation.
Diagnosis of IRIS requires exclusion of other possible causes, including treatment failure due to drug resistance or development of a different opportunistic infection.53
Treatment of IRIS is not always required, as the condition is self-limited. However, if the symptoms are severe enough to warrant therapy, corticosteroids such as prednisone at doses in the range of 1 mg/kg of body weight, given over four weeks, have been shown effective in a randomized trial.54 Most people can be managed successfully without interruption of ART or TB treatment and in any case, such interruption will not hasten resolution of IRIS.
A single randomized-controlled study has shown that a short course of prednisone given at the same time as ART initiation can reduce the frequency of symptomatic IRIS without increasing the risk of other opportunistic illness.55 People who should be considered for this intervention are those at high-risk of paradoxical IRIS, defined by CD4 count less than 100 × 106/L. It is important to ensure that patients are responding to TB therapy prior to using preemptive prednisone and that rifampin resistance is excluded. The presence of Kaposi’s sarcoma or active hepatitis B infection are additional contraindications.55
Recommendation
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We strongly recommend, in people with HIV responding to TB therapy and who are about to initiate antiretroviral therapy, and whose CD4 count is less than 100 x106, prednisone 40 mg/d for 14 days followed by 20 mg/d for 14 days to reduce the risk of symptomatic immune reconstitution inflammatory syndrome, unless rifampin-resistance, Kaposi’s sarcoma, and active hepatitis B infection are present as contraindications (good evidence).
Diagnostic considerations in people with both HIV and TB are discussed in Chapter 3: Diagnosis of TB disease and Drug-Resistant TB and Chapter 4: Diagnosis of TB Infection. Regimens used for treatment of latent TB infection in people with HIV are discussed in the Chapter 6: TB Preventive Treatment in Adults.
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