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CATIE
Dolutegravir vs. raltegravir
<p>Sean R. Hosein</p>
October 1, 2012

Dolutegravir is an experimental integrase inhibitor. In a study called Spring, researchers randomly assigned 822 HIV-positive volunteers who had never received potent combination anti-HIV therapy (commonly called ART or HAART) to one of the following regimens:

  • dolutegravir 50 mg once daily + two nukes (nucleoside analogues)
  • raltegravir 400 mg twice daily + 2 nukes

Spring is supposed to run for 96 weeks (about two years) and in this issue of TreatmentUpdate we have the results after one year.

Study details

The average profile of participants at the start of the study was as follows:

  • 86% men, 14% women
  • age - 36 years
  • CD4+ count - 360 cells
  • viral load - 35,000 copies/ml
  • HBV co-infection - 2%
  • HCV co-infection - 10%
  • 60% of participants used Truvada (tenofovir + FTC)
  • 40% of participants used Kivexa (abacavir + 3TC)

Results

After 48 weeks, the proportion of participants who had a viral load less than 50 copies/ml was as follows:

  • dolutegravir - 88%
  • raltegravir - 85%

The following proportions of participants had viral loads greater than 50 copies/ml at week 48 because of a lack of effectiveness:

  • dolutegravir - 1%
  • raltegravir - 3%

None of these differences were statistically significant.

Both integrase inhibitors caused a rapid decrease in viral load when treatment was initiated. For instance, after the first four weeks of the study, viral load in the blood fell below the 50-copy/ml mark in 70% of dolutegravir users and 65% of raltegravir users.

When the response to therapy was analysed by pre-study (baseline) viral load, the results were as follows:

Baseline viral load 100,000 copies/ml or less, the proportion with a viral load less than 50 copies/ml after one year of treatment was as follows:

  • dolutegravir - 90%
  • raltegravir - 89%

Baseline viral load greater than 100,000 copies/ml, the proportion with a viral load less than 50 copies/ml after one year was as follows:

  • dolutegravir - 82%
  • raltegravir - 75%

Here are the results when analysed by the nuke regimen that participants used in the study:

Proportion achieving a viral load less than 50 copies/ml

  • Kivexa + dolultegravir - 86%
  • Kivexa + raltegravir - 87%
  • Truvada + dolutegravir - 89%
  • Truvada + raltegravir - 85%

Rates of virologic failure (having a viral load greater than 50 copies/ml after week 24) were as follows:

  • dolutegravir - 5%
  • raltegravir - 7%

More than 80% of cases of virologic failure had viral loads between 50 and 400 copies/ml.

Side effects and complications

Common side effects were as follows:

Nausea

  • dolutegravir - 14%
  • raltegravir - 13%

Headache

  • dolutegravir - 12%
  • raltegravir - 12%

Runny nose

  • dolutegravir - 11%
  • raltegravir - 12%

Diarrhea

  • dolutegravir - 11%
  • raltegravir - 11%

Dizziness

  • dolutegravir - 6%
  • raltegravir - 6%

Chest infections

  • dolutegravir - 6%
  • raltegravir - 6%

Fever

  • dolutegravir - 5%
  • raltegravir - 5%

Fatigue

  • dolutegravir - 5%
  • raltegravir - 4%

Anxiety

  • dolutegravir - 3%
  • raltegravir - 5%

Depression

  • dolutegravir - 5%
  • raltegravir - 3%

Severe side effects were distributed as follows:

  • dolutegravir - 3% (including headache, dizziness, “feeling abnormal,” irregular heartbeats)
  • raltegravir - 5% (including nausea, stomach pain, rash, fatigue, elevated levels of liver and pancreatic enzymes in the blood)

Despite these results, only 2% of participants in each group left the study because of these or other symptoms.

Lab test results

No significant changes in creatinine occurred. Less than 5% of participants in each group had elevated levels of liver or other enzymes, suggestive of ongoing organ injury.

Changes in levels of lipids - cholesterol and triglycerides - in the blood were generally minimal in this study.

Focus on the kidneys

Neither dolutegravir nor raltegravir appeared to cause kidney dysfunction.

Summary

After one year, a regimen based on either dolutegravir or raltegravir seemed equally effective and safe as a first-line therapy for HIV-positive people.

- Sean R. Hosein

REFERENCE:

Raffi F, Rachlis A, Stellbrink H-J, et al. Once-daily dolutegravir (DTG: S/GSK 1349572) is non-inferior to raltegravir in antiretroviral naïve adults. 48-week results from Spring-2 (ING113086). In: Program and abstracts of the XIX International AIDS Conference, 22-27 July 2012, Washington, DC. Abstract THLBB04.



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