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Elvitegravir vs. raltegravir - two-year results




 

Raltegravir belongs to a group of drugs called integrase inhibitors and is sold under the brand name Isentress. Raltegravir is taken twice daily with or without food. In clinical trials raltegravir is a highly effective part of combination anti-HIV therapy (commonly called ART or HAART) and is generally safe.

Elvitegravir is an experimental integrase inhibitor. It needs to be taken with another drug that can raise, or boost, levels of elvitegravir in the blood. Such boosting drugs are called pharmacokinetic enhancers and examples of these are ritonavir (Norvir) and the new drug cobicistat.

On August 27, 2012, the U.S. Food and Drug Administration (FDA) approved a combination of the following four drugs (three of which - elvitegravir, tenofovir and FTC - have anti-HIV activity) in one pill:

  • elvitegravir
  • cobicistat
  • tenofovir (Viread)
  • FTC (emtricitabine, Emtriva)

This combination of four drugs in one pill taken once daily will be sold under the brand name Stribild and has been nicknamed the Quad. The Quad needs to be taken with a meal to maximize absorption and has been tested as a first regimen in HIV-positive people. There is also another group of people, those who have previously used several regimens - the treatment-experienced - and they could also benefit from elvitegravir. Therefore, Gilead Sciences, the manufacturer of elvitegravir (and the Quad) is testing elvitegravir in different populations, including treatment-experienced people.

In study 145, researchers in several countries recruited and randomly assigned 712 HIV-positive volunteers to one of the following treatment groups:

  • elvitegravir + a ritonavir-boosted protease inhibitor + a third drug
  • raltegravir + a ritonavir-boosted protease inhibitor + a third drug

The study was double blind and placebo controlled so that neither participants nor researchers knew who received elvitegravir until the study ended.

At the start of the study, an equal proportion of participants in each group were taking ritonavir with the following protease inhibitors:

  • darunavir (Prezista) - 58%
  • lopinavir (in Kaletra) - 19%
  • atazanavir (Reyataz) - 17%
  • fosamprenavir (Telzir) - 4%
  • tipranavir (Aptivus) - 2%

Participants were randomly assigned as follows:

  • elvitegravir-based regimen - 354 people
  • raltegravir-based regimen - 358 people

The average profile of participants at the time they entered the study was as follows:

  • 82% men, 18% women
  • age - 45 years
  • CD4+ cell count - 220 cells
  • HIV viral load - 32,000 copies/ml
  • HBV co-infection - 4%
  • HCV co-infection - 15%

About 60% of participants had HIV that was resistant to two or more classes of drugs.

Elvitegravir was taken at a dose of 85 mg once daily if used with atazanavir or lopinavir, otherwise it was taken at a dose of 150 mg, also once daily.

Raltegravir was taken at a standard dose of 400 mg twice daily.

The study was planned to last about two years (96 weeks) and we now present the results.

Results

A similar proportion of participants in each group achieved a viral load less than 50 copies/ml by the 48th week of the study, as shown below:

  • elvitegravir-based regimen - 59%
  • raltegravir-based regimen - 58%

Virologic suppression (less than 50 copies/ml) at week 96 was as follows:

  • elvitegravir-based regimen - 48%
  • raltegravir-based regimen  - 45%

On average, CD4+ counts increased by 200 cells two years after entering the study.

About 19% of participants in each group left the study prematurely for at least one of the following reasons:

  • side effects
  • not taking the study medicines as directed
  • pregnancy
  • death
  • failing to return for clinic visits

Side effects and complications

Side effects and complications graded as moderate to severe occurred in 68% of participants in each group. Here is the distribution of selected adverse effects:

Diarrhea

  • elvitegravir - 13%
  • raltegravir - 8%

Nausea

  • elvitegravir - less than 1%
  • raltegravir - 0%

Vomiting

  • elvitegravir - less than 1%
  • raltegravir - 0%

Sinus infection

  • elvitegravir - 5%
  • raltegravir - 4%

Chest infection

  • elvitegravir - 5%
  • raltegravir - 4%

Back pain

  • elvitegravir - 6%
  • raltegravir - 4%

Depression

  • elvitegravir - 6%
  • raltegravir - 6%

Thoughts of suicide

  • elvitegravir - 1%
  • raltegravir - 1%

Bone or joint pain

  • elvitegravir -5%
  • raltegravir - 3%

Rash

  • elvitegravir - 0%
  • raltegravir - less than 1%

Summary

Both integrase inhibitors were generally well tolerated with similar rates of effectiveness in this heavily treatment-experienced population.

- Sean R. Hosein

REFERENCE:

Elion R, Molina J-M, Arribas-Lopez J-R, et al. Efficacy and safety results from a randomized, double-blind, active-controlled trial of elvitegravir (once daily) vs. raltegravir (twice daily) in treatment-experienced HIV-infected patients. In: Program and abstracts of the XIX International AIDS Conference, 22-27 July 2012, Washington, DC. Abstract TUAB 0105.



 


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Information in this article was accurate in October 1, 2012. The state of the art may have changed since the publication date. This material is designed to support, not replace, the relationship that exists between you and your doctor. Always discuss treatment options with a doctor who specializes in treating HIV.