The safety of both dolutegravir- and raltegravir-containing regimens was good, with generally similar rates of reported adverse events (side effects and complications). Most side effects occurred during the first year of the study.
No participant taking dolutegravir in the second year of the study left prematurely because of side effects. However, three participants who were taking raltegravir had to stop due to side effects.
Side effects reported in the second year of the study were usually of mild or moderate intensity. Adverse events reported at week 96 were distributed as follows:
Stuffy nose and/or sore throat
No deaths related to the study medicines occurred.
Researchers did not find any clinically meaningful changes in levels of cholesterol in the blood of participants during the study.
Dolutegravir users had small increases in their level of creatinine (a waste product formed from the breakdown of muscle) in their blood as follows:
These small but sustained changes in creatinine occurred because dolutegravir interferes with the kidneys' ability to remove creatinine from the blood. The change appears to be harmless. For instance, researchers conducted additional and more direct tests of kidney health -- focusing on the ratio of the protein albumin to creatinine in the blood -- and did not find any significant differences in this ratio between dolutegravir and raltegravir users.
The small interference with creatinine release into the urine is also seen with other drugs, such as in these cases:
In such cases, the small increase in creatinine that occurs when these drugs are used does not appear to cause harm.
Overall, the researchers did not find any differences in changes in heart beat or abnormal heart rhythms in participants. However, one participant taking dolutegravir had a slightly abnormal heart rhythm.
As with all the clinical trials of dolutegravir, there have not been any reports of increased risk of heart attacks in participants in general and in users of abacavir in particular. This latter finding is consistent with an analysis of abacavir done by the U.S. Food and Drug Administration (FDA), which reviewed many randomized clinical trials and found no increased risk of cardiovascular complications in people who had used the drug.
In analysing the two-year data on dolutegravir-based regimens, researchers have found that this drug, when taken in a dose of 50 mg once daily, was as effective and safe as twice-daily raltegravir-based regimens. Results with dolutegravir were similar regardless of initial viral load or the additional nukes used in regimens -- abacavir + 3TC or tenofovir + FTC.
Dolutegravir and raltegravir caused a relatively low rate of side effects; when they did occur, such side effects were generally of mild-to-moderate intensity. This is similar to what has been seen in other trials of dolutegravir.
Other trials with dolutegravir are ongoing, including a clinical trial in women called Aria.