Emma Hitt, PhD

July 19, 2011

July 19, 2011 (Rome, Italy) — Similar and sustained efficacy against HIV infection was demonstrated over the course of 144 weeks with or without ritonavir in the ARIES study. Patients in both the simplification (abacavir [ABC]/lamivudine [3TC] + atazanavir [ATV]; ie, without ritonavir) and continuation (ABC/3TC + ATV/ritonavir) groups fared equally well.

Kathleen Squires, MD, from the Thomas Jefferson University Hospital, Division of Infectious Diseases, Philadelphia, Pennsylvania, presented the findings here during a poster session at the 6th International AIDS Society (IAS) Conference on HIV Pathogenesis, Treatment and Prevention.

"The main question that this study answers is whether you can keep people maintained without ritonavir," Dr. Squires told Medscape Medical News. According to her, ritonavir, in terms of an adverse effect profile and metabolic effects, is not very well tolerated. "This study showed that we were able to maintain efficacy, with no difference in virologic or immunologic efficacy, but [with] a more favorable lipid profile, and less hyperbilirubinemia," she said. "There was also no 'hit' in terms of resistance," she added.

The ARIES study included 379 antiretroviral therapy–naive patients who received ABC/3TC + ATV/RTV, followed by randomization (1:1) at week 36 to maintain or discontinue ritonavir for an additional 48 weeks. All patients had HIV-RNA levels of 50 or fewer copies/mL and were without virologic failure at randomization at 36 weeks. At week 84, 369 of the 379 participants chose to continue into an extension phase until week 144, during which they continued to receive their assigned regimen.

Similar and sustained efficacy was demonstrated over the course of 144 weeks in both groups of the study. During the extension phase, HIV-RNA levels of 50 or fewer copies/mL (time to loss of virologic response) was observed in 77% of participants in the unboosted groups vs 73% in the boosted group.

CD4+ cell counts increased substantially and to a comparable extent in both groups, and only about 3% of patients in either group were classified as having virologic failure from week 84 through week 144.

Both treatment regimens were generally well tolerated over the course of 144 weeks, although there was a higher number of treatment-related adverse events in the ATV/ritonavir group (23%) compared with in the ATV group (13%).

"Hyperbilirubinemia was the only treatment-related adverse event with ≥3% incidence from week 36 to week 144 (ATV/r arm 14% vs. ATV arm 6%)," the authors noted.

In terms of the clinical relevance of these findings, Dr. Squires noted that, at least for patients not tolerating ritonavir for whatever reason, this study would certainly suggest that stopping ritonavir is feasible.

"The caveat here is to think critically about the protease inhibitors being used," Dr. Squires said. We used atazanavir, which has been shown to work unboosted. However, for other protease inhibitors, such as darunavir, that have not been shown to work unboosted, we have no data to support this approach," she said.

"There are many patients on boosted atazanavir because of the efficacy and favorable tolerability profile of this protease inhibitor," said independent commentator Robert L. Murphy, MD, director of the Center for Global Health and John P. Phair Professor of Medicine at Northwestern University, Chicago, Illinois.

"Here we are dealing with a different paradigm than is usually considered — starting with boosted atazanavir, achieving viral suppression, then maintaining it with unboosted atazanavir," he told Medscape Medical News. "This simplified regimen is safe and also better tolerated than boosted atazanavir," he added.

This study was supported by ViiV Healthcare. Dr. Squires has disclosed that she receives funding for clinical grants and has consulting agreements with Bristol-Myers Squibb and GlaxoSmithKline. Bristol Myers Squibb donated study medication. Dr. Murphy reports acting as a consultant to Gilead and Merck.

6th International AIDS Society (IAS) Conference on HIV Pathogenesis, Treatment and Prevention: Abstract MOPE215. Presented July 18, 2011.


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