- Category: Experimental HIV Drugs
- Published on Wednesday, 20 July 2011 00:00
- Written by Liz Highleyman
The experimental HIV integrase inhibitor elvitegravir works as well as raltegravir (Isentress) for treatment-experienced people with extensive drug resistance, and was well-tolerated overall, according to data presented at the International AIDS Society Conference on HIV Pathogenesis, Treatment and Prevention (IAS 2011) this week in Rome.
Integrase inhibitors prevent HIV from integrating its genetic material into the chromosomes of a host cell, a requirement for viral replication. The sole approved drug in this class, raltegravir, has enabled many highly treatment-experienced patients to bring their viral load under control, but resistance can develop if it is used without enough other active drugs.
Elvitegravir is a next generation integrase inhibitor that can be taken once-daily, while raltegravir is taken twice-daily. But it must be used with a boosting agent, either ritonavir (Norvir) or the new pharmacoenhancer cobicistat. Elvitegravir and cobicistat are part of a single-tablet regimen known as the Quad pill (along with tenofovir/emtricitabine) that is being tested in treatment-naive people.
At the IAS meeting Jean-Michel Molina from Hopital Saint Louis in Paris reported findings from Study 183-0145, the first randomized, head-to-head study of elvitegravir vs raltegravir for treatment-experienced patients.
This international Phase 3 study included 702 participants. Most were men and the average age was 45 years. The mean CD4 cell count was approximately 260 cells/mm3, nearly half had less than 200 cells/mm3, and one-quarter had high viral load (> 100,000 copies/mL).
About two-thirds were resistant to two or more antiretroviral drug classes. However they were able to construct viable regimens including a fully active ritonavir-boosted protease inhibitor (the ritonavir acts as a booster for elvitegravir as well) and an active third agent such as etravirine (Intelence), maraviroc (Selzentry) or a nucleoside/nucleotide reverse transcriptase inhibitor. Boosted darunavir (Prezista) and tenofovir (Viread) were the most commonly used other drugs.
Participants were randomly assigned to receive either 150 mg elvitegravir once daily (dose adjusted if used with certain drugs) or 400 mg raltegravir twice-daily. The researchers looked at proportions of patients achieving viral load suppression at 48 weeks; the study is continuing through 96 weeks.
- Elvitegravir and raltegravir were equally effective, with 59% and 58%, respectively, achieving HIV RNA < 50 copies/mL.
- About 20% of participants in both arms experienced virological failure.
- CD4 cell gains were also similar, at around 140 cells/mm3 in both groups.
- Both study drugs were well-tolerated overall and few people discontinued due to side effects (3% vs 4%, respectively).
- Adverse events and laboratory abnormalities were generally similar.
- More elvitegravir recipients reported diarrhea (12% vs 7%).
- About 20% of patients who experienced virological failure developed integrase resistance mutations.
Based on these findings, the researchers concluded, elvitegravir was non-inferior to raltegravir when given with an active boosted protease inhibitor.
Due to cross-resistance patterns, elvitegravir is not likely to work well for people who have developed resistance to raltegravir. Once-daily dosing is an advantage, though perhaps less so for highly treatment-experienced individuals who must take other drugs twice-daily. On the other hand, the need for boosting is not a problem for people already taking a booster for protease inhibitors. Elvitegravir provides yet another option in an antiretroviral drug class that is well-tolerated and to date has not been linked to long-term toxicities.
Lead investigator Molina talked with HIVandHepatitis.com about the highlights of his study.
Jean-Michel Molina, IAS 2011, Rome, July 20, 2011:
J-M Molina, A LaMarca, J Andrade Villanueva, et al. Elvitegravir once-daily is non inferior to raltegravir twice-daily in treatment experienced patients: 48 week results from a phase 3 multicenter, randomized, double blind study. 6th International AIDS Society Conference on HIV Pathogenesis, Treatment and Prevention (IAS 2011). Rome, July 17-20, 2011. Abstract WELBB05.