First-line raltegravir. No evidence of comparative effectiveness

First-line treatment for HIV infection consists of a combination of antiretroviral drugs, specifically including a non-nucleoside reverse transcriptase inhibitor or an HIV protease inhibitor, usually boosted with ritonavir. Raltegravir, the only commercially available HIV integrase inhibitor, marketed since 2007 in the European Union, was initially reserved for patients with multiple treatment failure. It is now authorised for first-line use. Clinical evaluation of first-line raltegravir therapy is based on a comparative double-blind "non-inferiority" trial comparing raltegravir + tenofovir + emtricitabine versus efavirenz + tenofovir + emtricitabine in 566 patients. After 48 weeks, about 84% of the patients in the two arms had undetectable viral load. There are no trials versus other first-line combinations. The adverse effect profile of raltegravir is poorly documented. In the trial comparing raltegravir + tenofovir + emtricitabine with efavirenz + tenofovir+ emtricitabine, adverse effects of the two regimens were generally comparable. In practice, given the lack of firm evidence that raltegravir is a therapeutic improvement over existing first-line regimens, it is better to continue to reserve its use for patients with multiple treatment failure. Many satisfactory first-line combinations have been in use for several years.