Skip to main content

Dolutegravir, the Second-Generation of Integrase Strand Transfer Inhibitors (INSTIs) for the Treatment of HIV.

Publication ,  Journal Article
Dow, DE; Bartlett, JA
Published in: Infect Dis Ther
December 2014

The integrase strand transfer inhibitors (INSTIs) are the newest antiretroviral class in the HIV treatment armamentarium. Dolutegravir (DTG) is the only second-generation INSTI with FDA approval (2013). It has potential advantages in comparison to first-generation INSTI's, including unboosted daily dosing, limited cross resistance with raltegravir and elvitegravir, and a high barrier to resistance. Clinical trials have evaluated DTG as a 50-mg daily dose in both treatment-naïve and treatment-experienced, INSTI-naïve participants. In those treatment-naïve participants with baseline viral load <100,000 copies/mL, DTG combined with abacavir and lamivudine was non-inferior and superior to fixed-dose combination emtricitabine/tenofovir/efavirenz. DTG was also superior to the protease inhibitor regimen darunavir/ritonavir in treatment-naïve participants regardless of baseline viral load. Among treatment-experienced patients naïve to INSTI, DTG (50 mg daily) demonstrated both non-inferiority and superiority when compared to the first-generation INSTI raltegravir (400 mg twice daily) regardless of the background regimen. No phenotypically significant DTG resistance has been demonstrated in INSTI-naïve participant trials. The VIKING trials evaluated DTG's ability to treat persons with HIV with prior INSTI exposure. VIKING demonstrated twice-daily DTG was more efficacious than daily dosing when treating participants receiving and failing first-generation INSTI regimens. DTG maintained potency against single mutations from any of the three major INSTI pathways (Y143, H155, Q148); however, the Q148 mutation with two or more additional mutations significantly reduced its potency. The long-acting formulation of DTG, GSK1265744LA, is the next innovation in this second-generation INSTI class, holding promise for the future of HIV prevention and treatment.

Duke Scholars

Altmetric Attention Stats
Dimensions Citation Stats

Published In

Infect Dis Ther

DOI

ISSN

2193-8229

Publication Date

December 2014

Volume

3

Issue

2

Start / End Page

83 / 102

Location

New Zealand

Related Subject Headings

  • 3204 Immunology
  • 3202 Clinical sciences
  • 1115 Pharmacology and Pharmaceutical Sciences
  • 1107 Immunology
  • 1103 Clinical Sciences
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Dow, D. E., & Bartlett, J. A. (2014). Dolutegravir, the Second-Generation of Integrase Strand Transfer Inhibitors (INSTIs) for the Treatment of HIV. Infect Dis Ther, 3(2), 83–102. https://doi.org/10.1007/s40121-014-0029-7
Dow, Dorothy E., and John A. Bartlett. “Dolutegravir, the Second-Generation of Integrase Strand Transfer Inhibitors (INSTIs) for the Treatment of HIV.Infect Dis Ther 3, no. 2 (December 2014): 83–102. https://doi.org/10.1007/s40121-014-0029-7.
Dow, Dorothy E., and John A. Bartlett. “Dolutegravir, the Second-Generation of Integrase Strand Transfer Inhibitors (INSTIs) for the Treatment of HIV.Infect Dis Ther, vol. 3, no. 2, Dec. 2014, pp. 83–102. Pubmed, doi:10.1007/s40121-014-0029-7.

Published In

Infect Dis Ther

DOI

ISSN

2193-8229

Publication Date

December 2014

Volume

3

Issue

2

Start / End Page

83 / 102

Location

New Zealand

Related Subject Headings

  • 3204 Immunology
  • 3202 Clinical sciences
  • 1115 Pharmacology and Pharmaceutical Sciences
  • 1107 Immunology
  • 1103 Clinical Sciences