182 Challenges in the Treatment of Two Infections: HIV and Tuberculosis William Burman Denver Publ Hlth and Univ of Colorado Hlth Sci Ctr, USA

Tuberculosis (TB) is the single most common opportunistic infection among HIV-infected persons worldwide, and persons with HIV-related TB have a substantial risk of death and other opportunistic infections during the 6-9 month period of TB treatment.  Therefore, antiretroviral therapy should be a key intervention among persons with HIV-related TB.  However, treatment of two infections at the same time is challenging.  The side effect profiles of some antiretroviral and antituberculosis drugs are similar, making it difficult to determine the cause of common side effects like hepatitis, nausea, or skin rash.  Adherence to one form of multidrug therapy is challenging; taking multidrug therapy for two infections may require a significant preparation and effort.  The rifamycins are potent inducers of a number of hepatic enzyme systems, including cytochrome P450-3A4, and a number of antiretroviral drugs affect the same enzyme systems (most often, inhibiting CYP450).  Therefore, there are a number of drug-drug interactions  between the rifamycins and the non-nucleoside reverse transcriptase inhibitors and protease inhibitors.  Finally, the immune response following effective antiretroviral therapy can result in an exacerbation of the clinical manifestations of tuberculosis.  These immune reconstitution inflammatory syndromes among patients with HIV-related TB can cause substantial morbidity.  These challenges in using antiretroviral therapy during TB treatment result in controversies about the optimal timing of antiretroviral therapy in this clinical situation.  Despite the difficulties and challenges, there is growing evidence that starting antiretroviral therapy during TB treatment can result in marked decreases in the risk of other opportunistic infections and death.