(Last updated: February 12, 2014; last reviewed: February 12, 2014)
|Dolutegravir (DTG, Tivicay, GSK1349572)
For additional information see Drugs@FDA: http://www.accessdata.fda.gov/scripts/cder/drugsatfda/index.cfm
Tablet: 50 mg
|Selected Adverse Events
The International Antiviral Society-USA (IAS-USA) maintains a list of updated resistance mutations (http://www.iasusa.org/resistance_mutations/index.html), and the Stanford University HIV Drug Resistance database offers a discussion of integrase strand transfer inhibitor (INSTI) mutations (http://hivdb.stanford.edu/DR/INIResiNote.html). Poor virologic response to 50 mg dolutegravir twice daily may occur if INSTI-resistance Q148 substitution is present along with 2 or more additional INSTI-resistance mutations (see table above for list).
Dolutegravir is Food and Drug Administration (FDA)-approved in combination with other antiretroviral drugs for children aged 12 years and older, weighing at least 40 kg, and who are treatment-naive or treatment-experienced and INSTI-naive.
Efficacy and Pharmacokinetics
IMPAACT P1093 is an ongoing open-label trial of HIV-infected children with the plan to enroll down to age 4 weeks. FDA approval of dolutegravir down to age 12 years was based on data from 23 treatment-experienced, INSTI-naive adolescents. Intensive pharmacokinetic (PK) evaluations were performed on the first 10 participants (9 weighing ≥40 kg and receiving 50 mg, 1 weighing 37 kg and receiving 35 mg) and revealed comparable exposures to those seen in adults receiving 50 mg once daily.1 Nine of 10 participants achieved HIV RNA concentration <400 copies/mL at week 4 (optimal background therapy was added 5 to 10 days after dolutegravir was started). An additional 13 participants were then enrolled for evaluation of long-term outcomes. At 24 weeks, 70% had achieved HIV RNA concentration <50 copies/mL. No safety or tolerability concerns were identified.2 In addition, children aged ≥6 to <12 years are undergoing PK and longer-term follow up in P1093, using investigational tablets of lower strengths (or the 50 mg tablet if they weigh at least 40 kg). An oral pediatric granule formulation will also be studied.