Safety and Efficacy of Dolutegravir in Treatment-Experienced Subjects With Raltegravir-Resistant HIV Type 1 Infection: 24-Week Results of the VIKING Study

• Published in: The Journal of infectious diseases Vol. 207; no. 5; pp. 740 - 748
• Main Authors: Eron, Joseph J., Clotet, Bonaventura, Durant, Jacques, Katlama, Christine, Kumar, Princy, Lazzarin, Adriano, Poizot-Martin, Isabelle, Richmond, Gary, Soriano, Vincent, Ait-Khaled, Mounir, Fujiwara, Tamio, Huang, Jenny, Min, Sherene, Vavro, Cindy, Yeo, Jane
• Format: Journal Article
• Language: English
• Published: Oxford Oxford University Press 01.03.2013
• Subjects: Adult; Aged; Anti-HIV Agents - administration & dosage; Anti-HIV Agents - adverse effects; Anti-HIV Agents - pharmacology; Antiretroviral Therapy, Highly Active - methods; Biological and medical sciences; Drug Resistance, Viral; Female; Fundamental and applied biological sciences. Psychology; Heterocyclic Compounds, 3-Ring - administration & dosage; Heterocyclic Compounds, 3-Ring - adverse effects; Heterocyclic Compounds, 3-Ring - pharmacology; HIV Infections - drug therapy; HIV Infections - virology; HIV-1 - drug effects; HIV-1 - isolation & purification; Human immunodeficiency virus 1; Human viral diseases; Humans; Infectious diseases; Major and Brief Reports; MAJOR ARTICLES AND BRIEF REPORTS; Male; Medical sciences; Microbiology; Middle Aged; Miscellaneous; Pilot Projects; Plasma - virology; Pyrrolidinones - pharmacology; Raltegravir Potassium; RNA, Viral - blood; Treatment Outcome; Viral diseases; Viral diseases of the lymphoid tissue and the blood. Aids; Viral Load; Virology; Young Adult; Immunopathology; Antiretroviral agent; HIV-1 virus; Retroviridae; AIDS; Immune deficiency; Lentivirus; Virus; Infection; Resistance; Integrase inhibitor; Treatment; Efficiency; Viral disease; Antiviral; Human immunodeficiency virus; Raltegravir
• ISSN: 0022-1899; 1537-6613; 1537-6613
• DOI: 10.1093/infdis/jis750

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 log10 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.