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Dolutegravir in Treatment-Experienced People Who Have Not Previously Used an Integrase Inhibitor

August 2013

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Complications and Side Effects

Rates of side effects were similar whether participants were taking dolutegravir or raltegravir. There are at least two possible reasons for this. First, as a class, integrase inhibitors are generally well tolerated. Secondly, the background regimens for nearly all participants were combinations of protease inhibitors. These drugs can cause a range of side effects, mostly affecting the gastrointestinal tract (nausea, vomiting, diarrhea). Such side effects may have dwarfed any, more minor side effects that may have occurred with exposure to integrase inhibitors. Researchers noted that, in general, side effects were mostly of mild-to-moderate intensity.

No deaths occurred among participants who received dolutegravir. Although there were three deaths among raltegravir users, investigators found that none were caused by raltegravir (two cases of unrelated cancer and one case of multi-organ failure).

Some commonly reported side effects appear below. Bear in mind that many participants were taking complex regimens, so it is difficult to connect exposure to the study drugs with specific side effects.



  • dolutegravir: 20%
  • raltegravir: 18%

Lung/throat infections

  • dolutegravir: 11%
  • raltegravir: 8%


  • dolutegravir: 9%
  • raltegravir: 9%


  • dolutegravir: 6%
  • raltegravir: 6%


  • dolutegravir: 4%
  • raltegravir: 7%


  • dolutegravir: 5%
  • raltegravir: 5%

Joint pain

  • dolutegravir: 3%
  • raltegravir: 5%

Severely Abnormal Lab Test Results

ALT (alanine aminotransferase -- a liver enzyme)

  • Elevated levels of liver enzymes in the blood are suggestive of inflammation and injury to the liver. A similar proportion of participants receiving dolutegravir (3%) and raltegravir (2%) developed markedly increased levels of ALT (at least five times the upper limit of normal). These cases were reviewed by an independent panel of doctors and they judged the severe increases in liver enzymes to be related to HBV or HCV co-infection. Specifically, these rises in ALT levels likely occurred because upon entering the Sailing study and receiving a potent drug (integrase inhibitor), the immune systems of participants subsequently partially recovered. As a result, their immune systems were able to sense and attack liver cells infected with HBV or HCV. The ensuing attack by the immune system was responsible for the rise in liver enzyme levels. Another reason for elevated liver enzymes was the inadvertent removal of participants' anti-HBV therapy just prior to entering the study, as physicians focused on optimizing their anti-HIV regimens.


  • dolutegravir: 2%
  • raltegravir: 4%


  • Measuring levels of the waste product creatinine in the blood is one way to assess general kidney health. Higher-than-normal levels of creatinine are suggestive of kidney injury. In the present study, severe or serious elevations of creatinine in the blood were rare -- occurring in less than 1% of participants who received dolutegravir or raltegravir. Upon investigation, most of these cases were related to pre-existing conditions that can affect kidney health, such as higher-than-normal blood pressure, diabetes or infections (other than HIV).
  • However, as a group, dolutegravir users had slightly elevated levels of creatinine in the blood that persisted throughout the study. This effect was apparently not harmful and has also been seen in clinical trials where participants received the drug cobicistat, one of the drugs found in the pill called Stribild. In the case of Stribild users, the elevation in creatinine levels is also apparently not harmful.

Higher-than-normal blood sugar

  • dolutegravir: 1%
  • raltegravir: 2%

Elevated levels of creatine phosphokinase (CPK)

  • CPK is one of several enzymes (specifically called CPK-3) whose levels in the blood increase in cases of muscle inflammation and injury. In rare cases, muscle inflammation can occur with raltegravir and likely other integrase inhibitors. In the present study, elevated levels of CPK were distributed as follows:
  • dolutegravir: 2%
  • raltegravir: 1%

For the Future

Dolutegravir is expected to be approved as part of combination therapy for HIV-positive people in the U.S. by September and in Canada later this year.

A future issue of TreatmentUpdate will explore the issue of kidney health and dolutegravir.


Cahn P, Pozniak A, Mingrone, et al. Dolutegravir is superior to raltegravir in ART-experienced, integrase-naïve subjects: week 48 results from Sailing (ING111762). In: Program and abstracts of the 7th IAS Conference on Pathogenesis, Treatment and Prevention, 30 June to 3 July, 2013, Kuala Lumpur, Malaysia. Abstract WELBB03.

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This article was provided by Canadian AIDS Treatment Information Exchange. It is a part of the publication TreatmentUpdate. Visit CATIE's Web site to find out more about their activities, publications and services.

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