Management of individuals requiring antiretroviral therapy and TB treatment

Globally, tuberculosis (TB) is the commonest opportunistic infection in people living with HIV. Many co-infected patients first present with advanced immunosuppression and require antiretroviral therapy (ART) initiation during TB treatment. The incidence of TB in patients established on ART remains high. Co-treatment presents several management challenges. Recent data on these management issues are reviewed.

Efavirenz concentrations at standard doses are similar with and without concomitant rifampicin-based TB treatment. Nevirapine concentrations are frequently subtherapeutic during lead-in dosing at 200 mg daily in patients on rifampicin-based TB treatment, which may result in inferior virological outcomes. Hepatotoxicity occurred in three pharmacokinetic studies (conducted in healthy volunteers) of boosted protease inhibitors initiated in participants on rifampicin. Results of a clinical trial comparing efavirenz-based and nevirapine-based ART in patients on TB treatment, with no lead-in dosing of nevirapine, are awaited. Concurrent TB treatment increases the need for stavudine substitutions, mainly related to neuropathy. Consensus case definitions for TB immune reconstitution inflammatory syndrome (TB-IRIS) have been published. It is important to exclude TB drug resistance in patients with suspected TB-IRIS. A clinical trial demonstrated benefit of prednisone for treating TB-IRIS, reducing a combined endpoint of days of hospitalization and outpatient therapeutic procedures. Starting ART during TB treatment improved survival in patients with CD4 cell count less than 500 cells/mul, but the optimal interval between starting TB treatment and starting ART remains to be determined in several ongoing trials.

ART improves survival in co-infected TB patients, but is complicated by several management challenges that compromise programmatic implementation in resource-limited settings. Recent findings and the findings of ongoing studies will assist clinicians in dealing with these challenges.