paradoxical tuberculosis immune reconstitution inflammatory syndrome (tb-iris) treatment trial

Conditions: Immune Reconstitution Inflammatory Syndrome; Immune Reconstitution Syndrome; Tuberculosis; HIV-infection/Aids

Summary: tuberculosis is the most common opportunistic infection (oi) in hiv-infected persons worldwide, including in south east asia. significant numbers of patients experience tuberculosis-related paradoxical immune reconstitution inflammatory syndrome (tb-iris) after art initiation, yet the optimal treatment of tb-iris is unknown. a recent randomized-controlled trial showed the benefit of prednisone over placebo in reduction of days of hospitalization and invasive procedures. the investigators hypothesize that nonsteroidal anti-inflammatory drugs (nsaids) are as effective as corticosteroids for treatment of non-life threatening tb-iris in hiv-infected patients and hypothesize that adjunctive treatment with 3-hydroxy-3-methylglutaryl coenzyme a (hmg-coa) reductase inhibitors (statins) may improve the outcomes. this is a randomized controlled trial with a 2x2 factorial design to test the relative benefit of corticosteroids, nsaids, and statins for the symptomatic and immunologic control of tb-iris.


Eligibility criteria:
inclusion criteria: * hiv-1 infection documented by any locally licensed elisa or rapid hiv test kit. * age \>18 years * paradoxical tb-iris diagnosed by case definition (see section 5.2) * ability and willingness of the participant or legal guardian/representative to give informed consent. receiving appropriate art and anti-tb therapy, as judged by the site investigator exclusion criteria: * inability to take oral medication; * receiving chemotherapy, immunosuppressant, corticosteroid, nsaid, or statin medications; (asa is acceptable) * cannot or unlikely to attend regular clinic visits; * known allergy to nsaids, statins or corticosteroids; * liver transaminase \> 2 times the upper limit of normal within 60 days of enrollment; * history of myositis/myopathy; * high investigator suspicion of anti-tb treatment failure due to tb-resistance or medication non-adherence; * receiving ongoing azole anti-fungal for treatment or secondary prophylaxis of cryptococcosis, histoplasmosis or penicilliosis; * serious co-morbidities, co-infections, or laboratory values who should not receive nsaids, steroid or statins, as judged by the site investigator; * minimal iris reaction which is unlikely to require treatment, as judged by the site investigator; * pregnancy (a negative urine pregnancy test at screening is required for women of childbearing potential) or breast feeding; * receiving a hiv treatment regimen containing a protease inhibitor at study entry. exclusion for randomization a only * life threatening tb-iris, as defined by: * acute respiratory failure; pao2 \< 60 on room air or; * altered mental status or; * new focal neurological deficit or; * compression of the vital organs. * persons with uncontrolled diabetes mellitus; * impair kidney function, glomerular filtration rate \<60 ml/min; within 72 hours of consent * uncontrolled congestive heart failure * history of bleeding disorder; * platelet count \<100,000/µl; * history of significant gastrointestinal bleeding or ulceration; * prior adjunctive corticosteroid therapy for this tb episode for \> 48 hr; * pregnancy

Keywords: tb aids hiv iris immune reconstitution inflammatory syndrome anti-inflammatory treatment