Contrary to the encouraging findings of several small studies, newly reported data conclude that Kaletra (lopinavir/ritonavir) monotherapy is not a durable treatment option for HIV-positive people. Compared with patients who took Kaletra plus Retrovir (zidovudine) and Epivir (lamivudine), study volunteers who used Kaletra without other antiretrovirals were less likely to have undetectable viral loads after 48 weeks. Final data from the MONARK study were published in the February 1 issue of AIDS.
Researchers began studying Kaletra monotherapy several years ago in the hopes that taking only a protease inhibitor (PI) would be as effective at controlling HIV as a standard triple-drug regimen, but without the side effects of the two extra drugs. Small studies unveiled over the last few years have hinted that this may be true, and the use of a Norvir (ritonavir)-boosted PI like Kaletra as monotherapy has gained in popularity among European physicians.
For the MONARK study, Jean-Francois Delfraissy from the department of internal medicine and infectious diseases at Bicetre University Hospital in Le Kremlin-Bicetre, France, and his colleagues enrolled 136 HIV-positive patients who were relatively new to antiretroviral therapy. Eighty-three patients were randomized to receive Kaletra monotherapy and 53 patients received Kaletra plus Retrovir and Epivir.
After 48 weeks of treatment, 64 percent of those in the monotherapy group, compared with 75 percent of those in the combination therapy group, had viral loads of less than 50 copies, according to a strict “intent-to-treat” statistical analysis of the data. Though monotherapy appeared inferior, the difference between the two groups was small enough that it could have occurred by chance.
Differences between the groups became significant when the researchers used a more liberal “as-treated” statistical analysis. Comparing only those who remained on their assigned regimens for 48 weeks, 98 percent of people on the triple combination arm had viral loads below 50, compared with just 80 percent of those on Kaletra monotherapy. Moreover, three people in the monotherapy group who failed treatment developed protease resistance mutations compared with none of those on the three-drug regimen.
Though the proportion of people who experienced a serious side effect was statistically equivalent, more people,12 percent, in the monotherapy group experienced a serious side effect, compared with eight percent of patients in the triple-drug regimen group. This was contrary to expectations.
Delfraissy’s team concluded that Kaletra monotherapy cannot be recommended as a first-line therapeutic strategy.
