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Kaletra® (lopinavir/ritonavir) Based Regimens Demonstrate Favorable Resistance in Clinical Trials

BANGKOK, Thailand, July 14 /PRNewswire-FirstCall/ -- In two clinical studies, no primary protease inhibitor (PI) resistance was reported in antiretroviral-naive patients taking a Kaletra® (lopinavir/ritonavir) based regimen once daily (QD) or twice daily (BID) in combination with other antiretroviral agents. These data were presented at the 15th International AIDS Conference (IAC) in Bangkok, Thailand. The majority of patients in both studies maintained an undetectable viral load of less than 50 copies per milliliter (as measured by HIV RNA).

In study 720, no primary PI resistance has been reported through five years (252 weeks) of follow up in patients new to therapy (ARV-naive). Consistent with these findings, a separate trial of 190 ARV-naive patients, study 418, which evaluated Kaletra dosed once daily versus Kaletra dosed twice daily in combination with other agents, demonstrated no confirmed lopinavir resistance through one year (48 weeks) of therapy. The adult recommended dosage of Kaletra is 400/100 mg (three capsules or five milliliters of oral solution) twice daily with food.

"These resistance data, though based on a relatively small number of patients, are important because of the long duration of follow-up. They demonstrate that it is possible to achieve long term viral suppression while minimizing resistance. This may be especially important for ARV-naive patients, whose first regimen may be the best opportunity for success long- term," said Charles Hicks, M.D., lead study investigator, Duke University Medical Center, Durham, NC.

Study 418: Once-Daily vs. Twice-Daily Kaletra

Data from this randomized, open-label, study of patients new to therapy showed an HIV treatment regimen based on a once-daily dose of Kaletra had comparable viral suppression when compared to a twice-daily dose through one year (48 weeks). Patients received either Kaletra (800 mg lopinavir/200 mg ritonavir) once daily or Kaletra (400 mg lopinavir/100 mg ritonavir) twice daily. Patients in both arms also received once-daily emtricitabine and tenofovir.

In an intent-to-treat analysis (ITT), which categorizes any patient who does not complete the study as a treatment failure, the data showed 70 percent of patients in the once daily group and 64 percent of patients in the twice daily group achieved HIV RNA less than 50 copies per milliliter at week 48. These data demonstrated comparable effectiveness between the once-daily regimen and the twice-daily regimen of Kaletra with emtricitabine and tenofovir. Mean increases in CD4 cell count from baseline to the one-year visit were 185 and 188 cells per cubic millimeter in the once-daily and twice- daily arms, respectively.

Data also show that of 15 patients who had genotypic resistance testing results available (HIV RNA greater than 500 copies per milliliter), no patient (0/8 in the once-daily arm and 0/7 in the twice daily arm) was confirmed to have developed lopinavir resistance or tenofovir resistance. The incidence of emtricitabine resistance was low (2/8 in the once daily arm and 1/7 in the twice daily arm). Twenty-two patients (11 in the once-daily arm and 11 in the twice daily arm) had samples available for resistance testing (HIV RNA > 500 copies/mL) at any time between week 12 and week 48. Resistance testing results were available for 27 samples from 15 of the 22 patients.

"Kaletra dosed once daily was comparable in virologic efficacy to Kaletra dosed twice daily for patients new to therapy. This patient population could benefit from the development of more treatment options that provide once daily dosing schedules without sacrificing efficacy," said Jean-Michel Molina, M.D., lead study investigator, Department of Infectious Diseases, Saint-Louis Hospital, University of Paris, Paris, France.

"As part of our commitment to the HIV community, Abbott continues to explore additional treatment options with an aim to offer dosing flexibility to patients. In this study, a majority of patients had undetectable viral load, and no protease inhibitor resistance was detected after one year," said Scott Brun, M.D., global project head, Antiviral Global Project Team, Abbott Laboratories.

Kaletra was generally well tolerated in both arms of the study. The most common drug-related adverse events of moderate or greater intensity reported were diarrhea and nausea. Diarrhea was reported more frequently in patients on once-daily therapy (16 percent) versus patients on twice-daily therapy (5 percent).

Findings from study 418 demonstrated that the mean fasting lipid value changes from baseline to 48 weeks were lower in both the once-daily and twice- daily arms than in a previous Phase III study (M98-863) of Kaletra at 48 weeks in combination with stavudine and lamivudine with lipid values obtained under non-fasting conditions. In both the once-daily and twice-daily arms of this study, there was a mean total cholesterol increase from baseline of 27 milligrams per deciliter compared to 53 milligrams per deciliter in Study 863.

Similarly, both the once-daily and twice-daily arms of this study showed mean triglyceride value changes from baseline to 48 weeks were lower than those found in study 863 at 48 weeks. There was a mean increase from baseline of 82 milligrams per deciliter in the once-daily arm and 76 milligrams per deciliter in the twice-daily arm, versus 125 milligrams per deciliter in Study 863. In this study comparing once-daily and twice-daily therapy, the proportion of patients with triglyceride levels greater than 750 milligrams per deciliter was 5 percent in the once-daily arm and 4 percent in the twice- daily arm.

Study 720: Five-Year Data

Data from the randomized, uncontrolled, prospective Phase II study of 100 treatment-naive patients taking Kaletra in combination with lamivudine (3TC) and stavudine (d4T) show that of 17 patients out of 27 patients who met the criteria for resistance testing with resistance data available through 252 weeks, none demonstrated evidence of resistance to lopinavir (0/17) or stavudine (0/17). Three patients (3/17) demonstrated lamivudine resistance.

In addition, 64 percent of patients (64/100) had an undetectable viral load (HIV RNA less than 50 copies per milliliter) and 67 percent (67/100) had HIV RNA less than 400 copies per milliliter, using an intent-to-treat (ITT) analysis, which categorizes any patient who does not complete the study as a treatment failure. Of the 68 patients remaining on treatment (OT) at week 252, 94 percent (64/68) of patients had an undetectable viral load and 99 percent (67/68) had HIV RNA less than 400 copies per milliliter.

Patients in this open-label study, in which there was no comparator group, were given one of three doses of Kaletra in addition to the nucleoside analogues stavudine and lamivudine. After 48 weeks of therapy, all patients were converted to the same dose of Kaletra (400/100 mg BID) with stavudine and lamivudine.

Kaletra was generally well tolerated through 252 weeks of therapy. The most frequent adverse events were gastrointestinal in nature. Non-fasting lipid elevations were reported. At week 252, no Grade 3 total cholesterol elevation was observed in study patients. Grade 3 triglyceride values were observed in four patients. A minority of patients in this study employed appropriate lipid-lowering agents to treat these elevations through week 252. A decrease in total cholesterol and triglycerides were observed in these patients.

Additional Information About Kaletra

Kaletra should not be taken by patients who have had an allergic reaction to Kaletra or any of its ingredients, including lopinavir or ritonavir. Kaletra should not be used with certain medications. Taking certain other drugs with Kaletra could create the potential for serious side effects that could be life threatening. Patients should discuss all medicines, including those without a prescription and herbal preparations, with their physician or pharmacist.

In patients taking protease inhibitors, increased bleeding (in patients with hemophilia) and diabetes/high blood sugar have occurred. Pancreatitis and liver problems, which can be fatal, have been reported. Tell your doctor if you have or have had liver disease such as hepatitis. Changes in body fat have been seen in some patients receiving antiretroviral therapy. Some patients receiving Kaletra have had large increases in triglycerides and cholesterol. Varying degrees of cross-resistance among protease inhibitors have been observed.

In Kaletra clinical trials, the most commonly reported side effects of moderate to severe intensity were: abdominal pain, diarrhea, feeling weak or tired, headache and nausea; children experienced rash. This is not a complete list of reported side effects. Kaletra oral solution contains alcohol. Kaletra does not cure HIV infection or AIDS and does not reduce the risk of passing HIV to others.

About Abbott Laboratories

Abbott Laboratories has been a leader in HIV/AIDS research since the early years of the epidemic. In 1985, the company developed the first licensed test to detect HIV antibodies in the blood, and remains a leader in HIV diagnostics. Today, Abbott retroviral and hepatitis tests are used to screen more than half of the world's donated blood supply. To treat those with HIV, Abbott scientists have developed two protease inhibitors. Kaletra is the protease inhibitor market share leader in Europe, and is the most prescribed protease inhibitor in the United States.

Abbott Laboratories is a global, broad-based health care company devoted to the discovery, development, manufacture and marketing of pharmaceuticals and medical products, including nutritionals, devices and diagnostics. The company employs more than 55,000 people and markets its products in more than 130 countries.

Abbott's news releases and other information are available on the company's Web site at . Outside of the U.S., health care professionals can access additional information on Kaletra at .

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