Safety and efficacy of dolutegravir in treatment-experienced subjects with raltegravir-resistant HIV type 1 infection: 24-week results of the VIKING Study.

Abstract

BACKGROUND:

Dolutegravir (DTG; S/GSK1349572), a human immunodeficiency virus type 1 (HIV-1) integrase inhibitor, has limited cross-resistance to raltegravir (RAL) and elvitegravir in vitro. This phase IIb study assessed the activity of DTG in HIV-1-infected subjects with genotypic evidence of RAL resistance.

METHODS:

Subjects received DTG 50 mg once daily (cohort I) or 50 mg twice daily (cohort II) while continuing a failing regimen (without RAL) through day 10, after which the background regimen was optimized, when feasible, for cohort I, and at least 1 fully active drug was mandated for cohort II. The primary efficacy end point was the proportion of subjects on day 11 in whom the plasma HIV-1 RNA load decreased by ≥0.7 log(10) copies/mL from baseline or was <400 copies/mL.

RESULTS:

A rapid antiviral response was observed. More subjects achieved the primary end point in cohort II (23 of 24 [96%]), compared with cohort I (21 of 27 [78%]) at day 11. At week 24, 41% and 75% of subjects had an HIV-1 RNA load of <50 copies/mL in cohorts I and II, respectively. Further integrase genotypic evolution was uncommon. Dolutegravir had a good, similar safety profile with each dosing regimen.

CONCLUSION:

Dolutegravir 50 mg twice daily with an optimized background provided greater and more durable benefit than the once-daily regimen. These data are the first clinical demonstration of the activity of any integrase inhibitor in subjects with HIV-1 resistant to RAL.

• Authors: Joseph J Eron, Bonaventura Clotet, Jacques Durant, Christine Katlama, Princy Kumar, Adriano Lazzarin, Isabelle Poizot-Martin, Gary Richmond, Vincent Soriano, Mounir Ait-Khaled, Tamio Fujiwara, Jenny Huang, Sherene Min, Cindy Vavro, Jane Yeo, VIKING Study Group
• Journal: The Journal of infectious diseases (J Infect Dis) Vol. 207 Issue 5 Pg. 740-8 (Mar 01 2013) ISSN: 1537-6613 [Electronic] United States
• PMID: 23225901 (Publication Type: Clinical Trial, Phase II, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Anti-HIV Agents
• Heterocyclic Compounds, 3-Ring
• Oxazines
• Piperazines
• Pyridones
• Pyrrolidinones
• RNA, Viral
• Raltegravir Potassium
• dolutegravir

Topics

• Adult
• Aged
• Anti-HIV Agents (administration & dosage, adverse effects, pharmacology)
• Antiretroviral Therapy, Highly Active (methods)
• Drug Resistance, Viral
• Female
• HIV Infections (drug therapy, virology)
• HIV-1 (drug effects, isolation & purification)
• Heterocyclic Compounds, 3-Ring (administration & dosage, adverse effects, pharmacology)
• Humans
• Male
• Middle Aged
• Oxazines
• Pilot Projects
• Piperazines
• Plasma (virology)
• Pyridones
• Pyrrolidinones (pharmacology)
• RNA, Viral (blood)
• Raltegravir Potassium
• Treatment Outcome
• Viral Load
• Young Adult