15th Conference on Retroviruses and Opportunistic Infections Boston, MA February 3-8, 2008

Norvir/Reyataz Comparable to Kaletra for First-Line Therapy

February 4, 2008

By Tim Horn

Data from a study comparing Norvir (ritonavir)-boosted Reyataz (atazanavir) to Kaletra (lopinavir/ritonavir) suggest that both drugs have similar effectiveness in HIV-positive patients starting therapy for the first time. The 48-week study results, which also suggest potential side effect advantages in those using Norvir/Reyataz, were reported today at the 15th Conference on Retroviruses and Opportunistic Infections (CROI) in Boston.

Although the U.S. Department of Health and Human Services lists Norvir-boosted Reyataz as a “preferred” protease inhibitor (PI) option for individuals starting their first antiretroviral drug regimen, its safety and efficacy compared with Kaletra—considered to be the benchmark by which other first-line PI contenders are compared—has not been fully explored. Until now, Norvir-boosted Reyataz had only been compared with Kaletra in treatment-experienced patients.

Forty-eight-week data from the 96-week international CASTLE study were reported at CROI by Jean-Michel Molina, MD, of the Hospital St. Louis in Paris. First-time treatment takers have been randomized to use either once-daily Reyataz (300 mg) plus Norvir (100 mg) or twice-daily Kaletra (400 mg/100 mg), with both groups also using a standard dose of Truvada (tenofovir plus emtricitabine).

Upon entering the study, the 883 HIV-positive patients enrolled had average viral loads of 95,500 copies and CD4 counts of 205.

After 48 weeks, 78 percent of those in the Norvir-boosted Reyataz group had viral loads below 50 copies; in the Kaletra group, approximately 76 percent had viral loads below 50 copies. The difference between the two groups wasn’t statistically significant, meaning that it could have been due to chance.

CD4 count improvements were also similar in both groups. There was a 203 CD4 cell gain in the Norvir/Reyataz group, compared to a 219 gain in the Kaletra group.

Of the 106 patients who entered the study with fewer than 50 CD4 cells, more patients in the Norvir/Reyataz group (78 percent), compared with those in the Kaletra group (63 percent), were able to keep their viral load undetectable for 48 weeks. However, a direct comparison between the two study groups was not conducted by the researchers.

In the Norvir-boosted Reyataz group, patients who entered the study with low CD4 counts (i.e., less than 50 cells) were just as likely to benefit virologically from therapy as those with high CD4 cell counts (i.e., more than 200 cells). In the Kaletra group, statistically significant differences were reported—63 percent of those who entered the study with a CD4 count lower than 50 cells had an undetectable viral load after 48 weeks, compared with 80 percent of those who entered the study with a CD4 count of 200 cells or higher.

As for side effects, some time was spent reviewing changes in cholesterol and triglycerides, as these aren’t significantly affected by Reyataz and may be only moderately increased when a Norvir booster is used.

In CASTLE, total cholesterol levels increased by 12 percent in the Norvir/Reyataz group, compared with a 24 percent increase in the Kaletra group.  Triglyceride increases of 13 percent and 51 percent, respectively, we also reported. These differences were statistically significant, meaning that that they are too large to have occurred by chance.

Moderate increases in both “bad” LDL cholesterol and “good” HDL cholesterol were seen in both groups of patients, with no statistically significant differences between the two.

The authors also noted a lower incidence of diarrhea (2 percent versus 11 percent) and nausea (4 percent versus 8 percent) in the Norvir/Reyataz group, compared with the Kaletra group, respectively. It is important to note, however, that patients randomized to the Kaletra group began the study by taking the older, less-palatable capsule version of the drug; a better-tolerated tablet version is now used.

The 48-week conclusion offered up by the study authors is that Norvir-boosted Reyataz “demonstrated similar efficacy, a lower risk of gastrointestinal-related side effect and a significantly better lipid profile, compared with twice-daily [Kaletra],” in patients beginning HIV treatment for the first time.

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bhavin dalal, ahmedababd, 2008-02-12 03:27:11
reyataz+norvir is better than lopinavir/ritomavir.because it has minimum impact on lipid profile as compare to lopinavir/ritonavir.