Switiching from Kaletra (lopinavir/ritonavir) plus nucleoside reverse transcriptase inhibitors (NRTIs) to Kaletra monotherapy may be a safe and effective option for patients hoping to simplify their treatment without compromising long-term efficacy, according to study results reported at the 11th European AIDS Conference (EACS) this week in Madrid. A second, less successful Kaletra monotherapy study discussed at the conference, this time involving patients who started treatment using Kaletra without other antiretrovirals, provides some clues as to which patients are least and most likely to respond well to this still-experimental approach.
The first study, known as OK04, enrolled 198 HIV-positive people who had been on a stable regimen containing Kaletra plus two NRTIs for approximately 18 months. Upon entering the trial, the patients were divided into two groups: one group remained on the triple combination, while the other withdrew the two NRTIs and continued Kaletra by itself.
This strategy of starting with a potent regimen to get virus levels under control for several months, followed by a paring down to a simpler regimen, has produced mixed results in other studies. However, according to 48-week OK04 data presented at the International AIDS Conference in Toronto last year, people who simplified their treatment by going solo with Kaletra did just as well virologically as those who remained on triple-drug treatment.
The 96-week follow-up data from this study were reported at EACS by Jose Ramón Arribas, MD, of the HIV unit at the Hospital La Paz in Madrid.
Treatment failure was defined as having a confirmed viral load greater than 500, being lost to follow up or requiring a switch in treatment. Study volunteers taking Kaletra monotherapy were not counted as a failure if they had a viral load measurement greater than 500, added back their two NRTIs and then re-suppressed virus to less than 50 copies. This occurred in ten people in the Kaletra monotherapy group.
After 96 weeks, 13 percent of people in the monotherapy group had a treatment failure, compared with 22 percent of those who remained on triple-drug treatment. The percentage of people with a viral load of less than 50 copies after 96 weeks, was 77 percent in the monotherapy group and 78 percent in the triple combination group. This meant that switching to monotherapy, after virus was well controlled, was not statistically inferior to remaining on triple combination therapy.
Of note, eight people in the triple combination therapy group discontinued treatment because of side effects, compared with no patients in the Kaletra monotherapy group.
The second study, presented by Philippe Flandre, MD, from the Institut National de la Sante et de la Recherche Medicale (INSERM) in Paris, was a retrospective analysis of an earlier Kaletra monotherapy study. The MONARK trial compared Kaletra monotherapy to Kaletra plus two NRTIs: Retrovir (zidovudine) and Epivir (lamivudine). In this case, people who went on Kaletra monotherapy started it right away, without first getting their virus to undetectable with triple combination therapy.
It turned out that starting Kaletra monotherapy without first getting virus levels under control—as was done in the OK04 study—was inferior to triple-drug treatment. As reported in 2006 at the 15th International Drug Resistance Workshop in Sitges, Spain, 20 percent of people taking Kaletra monotherapy either failed to fully suppress virus or experienced a viral load rebound, compared with only 2 percent of people taking Kaletra plus two NRTIs.
Dr. Flandre’s talk highlighted an analysis looking at factors that predicted virologic success—defined as a viral load below 400 at week 24 and below 50 at week 48—or failure among those in the Kaletra monotherapy group. His team found that a person’s viral load before starting treatment; their virus subtype; and their viral loads at weeks one, two and four after starting treatment were associated with virologic success in the study.
Virus subtype and viral loads at week four were the strongest predictors of virologic success while on Kaletra monotherapy. Specifically, they found that people with HIV subtype B—the most common in the U.S.—were more likely to have virologic success than those with a non-B subtype. This result may be confounded a bit, however, by the fact that people with the non-B subtype were less likely to be adherent than people with the B subtype. Another predictive factor was the reduction in viral load after four weeks of treatment. Virologic success was much more likely among those who had viral loads below 400 after four weeks, compared with those who didn’t.
While results from OK04 and MONARK suggest that Kaletra monotherapy may have potential for some HIV-positive people, this therapeutic approach is still considered highly experimental and is not yet approved by the U.S. Food and Drug Administration or recommended by any of the published antiretroviral treatment guidelines.
Sources:
Arribas JR, Pulido F, Delgado R, et al. Lopinavir-ritonavir monotherapy vs. lopinavir-ritonavir and two nucleosides for maintenance therapy of HIV. Ninety-six week results of a randomized, controlled, open label, clinical trials (OK04 Study) [Abstract PS3/1]. 11th European AIDS Conference, Madrid, 2007.
Flandre P, Delaugerre C, Ghosn J, et al. Prognostic factors of virological success in antiretroviral-naïve patients receiving LPV/r monotherapy in the MONARK trial [Abstract PS1/2]. 11th European AIDS Conference, Madrid, 2007.
