Pharmacology of second-line antituberculosis drugs and potential for interactions with antiretroviral agents

摘要

An estimated 33.2 million people were living with HIV worldwide in 2007 . In 2006 there were an estimated 700000 cases of tuberculosis (TB) among HIV-positive people, and 200 000 deaths . HIV increases the risk of active TB and the mortality rate.When HIV-positive individuals are diagnosed with TB they usually have significant immunosuppression and require HIV therapy as well as TB treatment. First-line TB drugs are isoniazid, rifampicin, pyrazinamide and ethambutol. Co-administration with antiretrovirals often results in drug-drug interactions which may compromise efficacy or result in toxicity. Adverse effects are very common and include gastrointestinal intolerance, rashes and hepatotoxicity, which may necessitate stopping drugs and reintroducing them gradually. There are overlapping toxicity profiles such as peripheral neuropathy with isoniazid and didanosine, and anaemia with isoniazid, rifampicin, pyrazinamide and zidovu-dine. Whenever possible the most efficacious TB regimen should be continued,with adjustment to the antiretroviral drugs if necessary. However, sometimes it is unsafe to continue the first-line TB drugs and alternatives need to be found