The SWITCHMRK studies: substitution of lopinavir/ritonavir with raltegravir in HIV-positive individuals

Protease inhibitors potently suppress HIV viral load but are often associated with metabolic disturbances such as dyslipidemias and lipodystrophy. In addition to exercise, diet modification and anti-lipid therapies, one potential management strategy for HIV-positive patients with dyslipiclemia is to switch any antiretrovirals that may be exacerbating the condition to more lipid-neutral drugs. The SWITCHMRK studies examined the effects of substituting lopinavir/ritonavir, a protease inhibitor known to cause dyslipidemias, with the integrase inhibitor raltegravir. Participants who switched from lopinavir/ritonavir to raltegravir experienced an improvement in cholesterol and triglycerides at 12 weeks; however, a large proportion of patients in the raltegravir arms did not maintain HIV virologic suppression at less than 50 copies/ml at week 24. Further analyses are underway to determine why more patients in the raltegravir arms experienced increased virologic failure and to determine whether switching lopinavir/ritonavir with raltegravir may be appropriate for specific subgroups of patients.