The study results of a three-year efficacy and tolerability of a Kaletra-based regimen in 100 patients new to antiretroviral therapy (naive) was presented at the 14th International AIDS Conference in Barcelona. This data demonstrated that a drug regimen including Kaletra provided viral suppression (as measured by viral load) and immunologic response (as measured by CD4 levels). Additionally, of the six patients who experienced viral rebound (HIV RNA >400 copies/mL) and had genotypic analysis available, none showed detectable protease inhibitor (PI) resistant mutations through the three years of study.
This ongoing Phase II study (M97-720) of 100 antiretroviral (ARV)-naïve patients was designed to evaluate different doses of Kaletra and had no comparator group. Patients were randomized to one of three doses of Kaletra in addition to stavudine (d4T) and lamivudine (3TC). After 48 weeks, all patients were converted to open-label 400/100 mg twice-daily dosing of Kaletra with continued NRTIs twice daily.
The Kaletra-based regimen provided viral suppression through three years (156 weeks) of treatment. In an intent-to-treat (ITT) analysis where non-completers were considered treatment failures, 75 percent of patients maintained undetectable viral levels (HIV RNA<400 copies/mL). For patients with a detectable viral load, viral samples were tested for genotypic resistance. Of the patients with a detectable viral load and whose viral isolates could be analyzed, none were found to have mutations associated with PI resistance. Patients also achieved significant increases in CD4 cell counts. From baseline to week 156, the average increase in CD4 cell count was 356 cells/mm3. An immune response was observed in all patient groups regardless of baseline CD4 measures; this includes 36 percent of patients who entered the study with significantly low CD4 counts (<200 cells/mm3). By week 156, 78 of 100 patients remained on the study drug, and of the twenty-two patients who discontinued, five were due to Kaletra-related adverse events.
Tolerability of Kaletra plus the two NRTIs was similar in both men and women. Drug discontinuations were not significantly different between females and males, and patient discontinuations due to gastrointestinal-related adverse events or lipid elevations were uncommon. Some gender-specific differences were noted, with triglyceride elevations occurring less frequently among women and nausea occurring less frequently in men.