Bob Roehr

October 28, 2008

October 28, 2008 (Washington, DC) — Results from 2 trials reported here at the 48th Annual ICAAC/IDSA 46th Annual Meeting, a joint meeting of the American Society for Microbiology and the Infectious Diseases Society of America, show continued strong results for both darunavir and atazanavir with ritonavir in patients with HIV infection who have not previously received treatment.

In the ARTEMIS study, darunavir/ritonavir (DRV/r; Prezista, Tibotec) appears to be "noninferior and statistically superior" to lopinavir/ritonavir (LPV/r; Kaletra, Abbott ) in treatment-naïve patients. This is the first look at the 96-week data that was the basis for the move earlier this week by the US Food and Drug Administration granting an expanded label indication for darunavir in treatment-naïve patients.

The 689 patients were randomized to receive either DRV/r 800/100 mg once daily or a total daily dose of LPV/r 800/200 mg. Tenofovir disoproxil fumarate/emtricitabine (300/200 mg) completed the regimens.

Although both groups performed well, the data show a continued divergence of outcomes between them, to the benefit of DRV/r. At week 96, a greater percentage of patients in the DRV/r group had fewer than 50 HIV RNA copies/mL (79% vs 71%), and the median change in absolute CD4 cell count was greater (+188 vs +171). This continues a trend observed in week-48 data, reported by Medscape HIV/AIDS when those data were released.

Anthony Mills, MD, a physician in private practice in Los Angeles, California, and lead author of the study, participated in studies of both treated and treatment-naïve patients, sponsored by Tibotec. "That gave me a breadth of knowledge about how useful and potent it is in all of those situations very early on," he told Medscape HIV/AIDS.

"The thing I am most impressed with is the tolerability. Most of the patients were newly diagnosed and didn't know a lot about HIV. So, they couldn't figure out why we kept asking about adverse effects and made them keep coming back every 2 months," he said.

He said that LPV/r is a good drug and he has many patients taking it, but a portion of them have issues with tolerability, which play out over time. He believes tolerability explains much of the difference in dropouts and virologic failure between the 2 groups.

Dr. Mills strongly favors the first-line use of the most powerful agents, rather than saving them for second-line use after initial or subsequent failure. He said: "We used to always sequence [serial use of drugs after failure], then Abbott came along with [LPV/r] and said, if you plan for success, then you don't have to plan for failure. That changed my mind set years and years ago."

Darunavir is "a great new agent to be used as first-line therapy; the tolerability is incredible. We did not see the development of resistance, which makes me confident about using it early on. I'm not concerned that I'm going to breed a resistant virus that is going to be a problem to treat later on. It provides a really great quality of life for patients."

Douglas Ward, a physician practicing in Washington, DC, told Medscape HIV/AIDS that the study confirms and reinforces what many doctors have already integrated into their clinical practice.

Across the aisle, a poster on the CASTLE study extended the comparison of once-daily atazanavir/ritonavir (ATV/r; Reyataz) and twice-daily LPV/r in treatment-naïve patients.

Earlier 48-week data demonstrated the comparability of the 2 therapies. By week 96, they were still comparable but had begun to inch apart in nonconcordant, but not statistically or clinically significant, ways.

Those in the ATV/r group were more likely than those in the LPV/r group to have fewer than 50 HIV RNA copies/mL (74% vs 68%; P < .05). The ATV/r group showed a slightly lower increase in mean CD4 cell count from baseline (268 vs 290), although both groups continued to show an upward slope on that curve. Both measures in this intent-to-treat analysis likely were affected by the higher dropout rate in the LPV/r group.

Virologic failure in both groups was ~7%. ATV/r showed better gastrointestinal tolerability. It also showed an improved fasting lipid profile over baseline (total-cholesterol to high-density-lipoprotein-cholesterol ratio of >5; 23% at baseline and 17% at week 96), whereas the LPV/r group showed no improvement and was more likely to initiate lipid-lowering therapy (2% vs 9%).

"Historically, there has been some concern that, with more advanced patients — those with low CD4 counts and a high viral load — atazanavir didn't do quite as well. What these data show is that it is just as potent a drug" in all patient populations, Judith Absalon, MD, senior author of the poster and an employee of the sponsor, Bristol-Myers Squibb, told Medscape HIV/AIDS.

"The tolerability profile is better" and physicians should be thinking about atazanavir as part of their treatment repertoire, she said.

Douglas Ward, MD, a physician practicing in Washington, DC, told Medscape HIV/AIDS that the studies confirm and reinforce what many physicians are already doing in their clinical practices.

The ARTEMIS study was funded by Tibotec. Dr. Mills has compensated research, advisory, and speaking ties with most of the companies producing antiretroviral drugs. Dr. Ward has disclosed no relevant financial relationships. The CASTLE trial was sponsored by Bristol-Myers Squibb. Dr. Absalon is an employee of Bristol-Myers Squibb.

48th Annual ICAAC/IDSA 46th Annual Meeting: A Joint Meeting of the American Society for Microbiology and the Infectious Diseases Society of America: Abstracts H-1250c and H1250d. Presented October 26, 2008.

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