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May 14, 2007
Kaletra Regimens 'Forgiving' of Missed Doses (Reuters Health)
by Martha Kerr
Adherence rates to lopinavir/ritonavir regimens that fall below 95% can still bring about high rates of virologic suppression in HIV infection, according to a new study.
Dr. Jonathan Shuter and associates at Montefiore Medical Center, Center for AIDS Research, in the Bronx, New York, prospectively studied 64 HIV-infected individuals on a regimen of lopinavir plus ritonavir, evaluating them according to adherence rates. Eighty percent of the study group had been diagnosed with AIDS.
Most of the subjects had received highly active antiretroviral therapy (HAART) for more than seven years.
Mean adherence overall was 73%. Eighty percent had viral loads below 400 copies/ml and 59% achieved viral loads below 75 copies/ml.
"In this study, all subjects were receiving twice daily dosing of lopinavir/ritonavir," Dr. Shuter told Reuters Health. "This translates to 60 doses in a 30-day month. Any subject taking less than 57 doses per month would have a calculated adherence rate below 95%. A patient missing just one dose per week would have a calculated adherence rate of 93%," he explained.
High levels of viral suppression were seen in all groups, even in those with the lowest adherence rates. Only 20% of patients achieved adherence rates above 95%, the investigators report in the May 1st issue of the Journal of Acquired Immune Deficiency Syndrome.
Dr. Shuter calls the lopinavir/ritonavir regimen "forgiving" and says the forgiveness is likely attributable to two factors. "One is the improved pharmacokinetic properties of lopinavir/ritonavir as compared to unboosted protease inhibitors," he said. "The second is the low frequency of resistance mutations in recipients of lopinavir/ritonavir therapy."
"Factor 1 makes it more likely that a patient missing a dose will maintain therapeutic levels of drug, and Factor 2 makes it less likely for non-adherent patients to evolve resistance against the agent," he continued.
Dr. Shuter said that recent research data demonstrate "high rates of virologic suppression in the face of moderate adherence rates in recipients of non-nucleoside reverse transcriptase based (primarily nevirapine) therapy. The forgiveness of other boosted protease inhibitor-based regimens or of unboosted atazanavir is not known."
