The immunomodulatory role of prednisone in TB-HIV co-infected patients and assessment of its impact on clinical and TB treatment outcomes

Tuberculosis (TB) is the most common opportunistic infection amongst HIV-infected patients in sub-Saharan Africa. In South Africa up to 42% of patients starting antiretroviral therapy are taking tuberculosis treatment. Up to 54% of these patients develop TB-IRIS, resulting in considerable morbidity. Treatment with prednisone was shown to reduce this morbidity in a previous trial conducted in Cape Town. We are currently conducting a trial (Pred-ART) to study the effect of prednisone as a preventive strategy for TB-IRIS in HIV-TB co-infected patients who are identified as being at high risk for TB-IRIS and starting ART. This trial provides us with an ideal opportunity to address certain questions related to the effects of prednisone in patients with HIVassociated TB co-infection: on the outcome of TB treatment, time to sputum culture positivity, and the risk of relapse, on residual pulmonary impairment after completion of TB treatment as well as health related quality of life. We hypothesize that prednisone therapy inhibits or prevents inflammation early in the co-treatment of HIV-associated TB coinfection, resulting in less pulmonary scarring and ultimately improved pulmonary function. We also hypothesize that improved pulmonary function will be reflected by higher HR-QoL scores. In addition, immunological studies will be conducted in order to understand the mechanisms underlying the clinical findings.