An Overview of Dolutegravir
May 29, 2013
Other Names: DTG, GSK1349572, S/GSK1349572
What is an investigational drug?
An investigational drug is one that is under study and is not approved by the U.S. Food and Drug Administration (FDA) for sale in the United States. Medical research studies are conducted to evaluate the safety and effectiveness of an investigational drug. These research studies are also called clinical trials. Once an investigational drug has been proven safe and effective in clinical trials, FDA may approve the drug for sale in the United States.
What is dolutegravir?
Dolutegravir is an investigational drug that is being studied for the treatment of HIV infection.
Dolutegravir belongs to a class (group) of HIV drugs called integrase inhibitors.2 Integrase inhibitors block an HIV enzyme called integrase. (An enzyme is a protein that starts or increases the speed of a chemical reaction.) By blocking integrase, integrase inhibitors prevent HIV from multiplying and can reduce the amount of HIV in the body.
Dolutegravir does not require boosting with an additional drug. (Boosting involves the use of a second drug to increase the effectiveness of the main [first] drug.)6
How are clinical trials of investigational drugs conducted?
Clinical trials are conducted in "phases." Each phase has a different purpose and helps researchers answer different questions.7
In most cases, an investigational drug must be proven safe and effective in a Phase III clinical trial to be considered for approval by the FDA for sale in the United States. Some drugs go through the FDA's accelerated approval process and are approved before a Phase III clinical trial is complete. After a drug is approved by the FDA and made available to the public, researchers track its safety in Phase IV trials to seek more information about the drug's risks, benefits, and optimal use.7
In what phase of testing is dolutegravir?
Dolutegravir is currently being studied in several Phase III clinical trials.2
A new drug application (NDA) for dolutegravir for the treatment of HIV infection in adults and adolescents was submitted to the FDA in December 2012.4
A dolutegravir expanded access program (ING114916 Study) is currently open to HIV-infected adults in whom the HIV medicines raltegravir or elvitegravir do not work because of drug resistance and who have limited treatment options.5
What have recent studies shown about dolutegravir?
In a Phase III study (known as the SPRING-2 Study), unboosted dolutegravir taken once daily was compared to the FDA-approved integrase inhibitor raltegravir (brand name: Isentress) taken twice daily in HIV-infected participants. The participants had never taken HIV medicines before entering the study (treatment-naive). During the study, participants also received additional HIV medicines as part of their background regimens. (A background regimen is a combination of drugs that are not being studied as the investigational drug[s] in the clinical trial, but are being given to help control a participant's HIV infection.) In this study, dolutegravir proved as effective as raltegravir. In terms of safety, dolutegravir was comparable to raltegravir. The most common side effects that occurred were nausea, headache, common cold, and diarrhea.8
In another Phase III study (known as the SINGLE Study), unboosted dolutegravir taken once daily was compared to once-daily tenofovir disoproxil fumarate/emtricitabine/efavirenz (brand name: Atripla), an FDA-approved combination drug, in treatment-naive adults. Participants receiving dolutegravir were also given a background regimen of abacavir/lamivudine (brand name: Epzicom). Results indicated that in treatment-naive adults, dolutegravir was more effective and caused fewer side effects than Atripla.9
The SAILING Study is a Phase III study that compared unboosted dolutegravir taken once daily to raltegravir taken twice daily in participants who had taken HIV medicines previously but had never taken integrase inhibitors before entering the study (treatment-experienced but integrase inhibitor-naive). All study participants also received a background regimen. Early results demonstrated that in treatment-experienced, integrase inhibitor-naive adults, dolutegravir was more effective in reducing viral load (the amount of HIV in the blood) than raltegravir and caused side effects similar to those caused by raltegravir.10
Dolutegravir has also been studied in treatment-experienced adults for whom other HIV medicines are not working because of drug resistance. In this study, called the VIKING-3 Study, dolutegravir taken twice daily along with an optimized background regimen proved effective in reducing viral load. (An optimized background regimen is a combination of drugs, chosen on the basis of a person's resistance test results and treatment history, that are not being studied as the investigational drug[s] in the clinical trial, but are given to help control a participant's HIV infection.) In terms of safety, dolutegravir was well tolerated and the most common side effects were diarrhea, nausea, and headache.11
Additional studies of dolutegravir are under way, including a study of a fixed-dose combination (FDC) drug containing dolutegravir and abacavir/lamivudine. (Fixed-dose combination drugs include two or more drugs in a single dosage form, such as a capsule or tablet.)12
This article was provided by AIDSinfo. Visit the AIDSinfo website to find out more about their activities and publications.
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