A Slice of Atazanavir, but Hold the Ritonavir: Switch to Unboosted Dose Still Effective After 120 Weeks, With Good Lipid Findings

Switching from a regimen containing Reyataz (atazanavir) boosted with Norvir (ritonavir) to a regimen that cuts out the Norvir doesn't hurt the regimen's effectiveness and doesn't compromise its safety, according to 120-week results from a study presented at ICAAC 2010.

A study of such length is somewhat unusual among clinical trials comparing antiretroviral regimens. But uncertainty over the staying power of a regimen containing unboosted Reyataz led the study researchers to extend their trial about a year beyond its original end date.

Reyataz, a protease inhibitor, is one of the more common options out there for HIV-positive people starting their first treatment regimen. It's usually taken as a single, 300-mg pill once daily along with 100 mg of Norvir to help boost the regimen's effectiveness at suppressing viral load. But Norvir is also believed to carry its share of side effects: Shortly after people begin taking it, they may experience any number of gastrointestinal problems, such as nausea and diarrhea; and over the long term, Norvir may be associated with lipid problems, including elevated cholesterol and triglycerides.

The ARIES study was designed to see whether people could safely switch from boosted Reyataz to unboosted Reyataz in hopes of avoiding some of those long-term side effects. Initially, the study enrolled 515 HIV-positive people who had never been on antiretrovirals and started them all on a regimen of Reyataz, Norvir and the drugs in the fixed-dose combination pill Epzicom (abacavir/3TC, Kivexa). Those who had an undetectable viral load after 36 weeks were then split into two groups; one continued the same regimen, while the other dropped the Norvir and began taking a higher dose of Reyataz (400 mg once daily). Previously released study results (at 84 weeks) showed that those who switched did as well as those who didn't. Here at ICAAC 2010, we saw "extended" results out to 120 weeks, involving a total of 369 people from the original study.

Those extended results continued to demonstrate that unboosted Reyataz was "non-inferior" to boosted Reyataz. The percentage of people with a viral load under 50 was virtually identical across both study arms (84 percent in the unboosted arm vs. 83 percent in the boosted arm). Three people in the unboosted arm (vs. four in the boosted arm) saw their regimens stop suppressing HIV; none of them showed any sign of major drug resistance to protease inhibitors, although that had been one of the concerns associated with cutting Norvir out of the equation. CD4 increases were identical across both arms (up 290, on average; about half of the study participants had started the trial with a CD4 count of 200 or less).

When comparing key side effects, the results were about as expected. Rates of gastrointestinal problems were similar across both arms, which makes sense, since the gastrointestinal effects associated with Norvir typically fade within the first several weeks. Unusually high levels of bilirubin, a possible indicator of liver function impairment that is sometimes associated with Reyataz, occurred less frequently in the unboosted arm (6 percent) than the boosted arm (14 percent). And unsurprisingly, lipid levels looked significantly better among people in the unboosted arm: Total cholesterol, LDL cholesterol and triglycerides all dropped significantly more in the unboosted arm than in the boosted arm (where those values usually tended to rise).

To be clear: These findings don't say that people should switch to unboosted Reyataz if they're doing well on boosted Reyataz. Many clinicians are understandably nervous about the idea of "fixing what ain't broke," particularly given a number of other studies that tend to show a higher risk of treatment failure after people switch to a new regimen from one that was working fine.

But that having been said, within the context of these clinical trial results, it does look like removing Norvir from the equation won't do more harm. And in the case of a person with high lipid levels, this study suggests it might actually do some good. Additionally, as one study author noted, removing Norvir from the study regimen cut its price tag by 25 percent. That may not matter much either way for most HIV-positive people in the U.S. who have solid health care coverage. But for cash-strapped health care facilities and AIDS Drug Assistance Programs, study findings such as these could become more relevant.

Myles is the editorial director of TheBody.com and TheBodyPRO.com.

Reference

Squires K, DeJesus E, Bellos N, et al. Sustained virologic efficacy of atazanavir versus atazanavir/ritonavir, each in combination with abacavir/lamivudine over 120 weeks: The ARIES Trial. In: Program and abstracts of the 50th Interscience Conference on Antimicrobial Agents and Chemotherapy; September 12-15, 2010; Boston, Mass. Abstract H-204.

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