What Role, Kaletra?
Kaletra (lopinavir), Abbott Laboratories' recently approved protease inhibitor (PI), has caused a great deal of confusion among researchers and healthcare providers. The reason for this is that nobody fully understands this drug's resistance profile. In one study presented at the 8th CROI, a team of researchers from Abbott examined 96 HIV samples collected from people on treatment for the first time who saw a rebound in their viral load while taking either Viracept (nelfinavir) or Kaletra with Zerit (d4T) and Epivir (3TC). Of the 65 samples collected from those who failed the Viracept regimen, 32% had mutations that were clearly associated with Viracept resistance. Of the 41 samples collected from patients who failed the Kaletra regimen, none contained mutations in the virus's protease gene (42% did contain mutations associated with Epivir resistance).
On the surface, the lack of Kaletra mutations might be considered to be a good thing. However, without information about its resistance profile, it is difficult to determine which protease inhibitor people can switch to if they start therapy with Kaletra and eventually fail the drug. Fortunately, another study presented at the 8th CROI helped shed some light on this situation. Upon testing samples collected from people who had failed other protease inhibitors in the past, researchers at Abbott concluded that people who are no longer responding to Kaletra may benefit from switching to either Fortovase (saquinavir) or Agenerase (amprenavir). On the other hand, patients failing Kaletra were less likely to respond upon switching to Norvir (ritonavir) or Crixivan (indinavir).
What about patients who have failed other protease inhibitors in the past and need to switch to Kaletra? Of all the mutations that can arise during therapy with other protease inhibitors, 11 are associated with cross-resistance to Kaletra. As a rule of thumb, researchers have determined that HIV containing six or fewer of these 11 mutations will still likely respond to Kaletra. Strains of HIV containing seven or more of these 11 mutations are less likely to respond to Kaletra therapy. Many laboratories currently conducting drug-resistance testing are aware of this new information, so people hoping to use Kaletra as a salvage protease inhibitor can benefit from the information produced by these tests.
This article was provided by AIDS Community Research Initiative of America. It is a part of the publication CRIA Update. Visit ACRIA's website to find out more about their activities, publications and services.