Dolutegravir in Antiretroviral-Experienced Patients With Raltegravir- and/or Elvitegravir-Resistant HIV-1: 24-Week Results of the Phase III VIKING-3 Study

• Published in: The Journal of infectious diseases Vol. 210; no. 3; pp. 354 - 362
• Main Authors: Castagna, Antonella, Maggiolo, Franco, Penco, Giovanni, Wright, David, Mills, Anthony, Grossberg, Robert, Molina, Jean-Michel, Chas, Julie, Durant, Jacques, Moreno, Santiago, Doroana, Manuela, Ait-Khaled, Mounir, Huang, Jenny, Min, Sherene, Song, Ivy, Vavro, Cindy, Nichols, Garrett, Yeo, Jane M.
• Format: Journal Article
• Language: English
• Published: Oxford Oxford University Press 01.08.2014
• Subjects: Adult; Anti-HIV Agents - therapeutic use; Antiretrovirals; Antivirals; Biological and medical sciences; Dosage; Drug Resistance, Viral; Female; Fundamental and applied biological sciences. Psychology; Genetic mutation; Heterocyclic Compounds, 3-Ring - therapeutic use; HIV; HIV 1; HIV infections; HIV Infections - drug therapy; HIV Infections - virology; HIV-1 - drug effects; HIV/AIDS; Human immunodeficiency virus 1; Humans; Infectious diseases; Integrase inhibitors; Major and Brief Reports; Male; Medical sciences; Microbiology; Middle Aged; Miscellaneous; Pilot Projects; Pyrrolidinones - pharmacology; Quinolones - pharmacology; Raltegravir Potassium; RNA; RNA, Viral - blood; Viral Load; Virology; Viruses; Human; Antiretroviral agent; HIV-1 virus; Retroviridae; Elvitegravir; Lentivirus; Virus; Infection; Resistance; Integrase inhibitor; Antiviral; Human immunodeficiency virus; Raltegravir; dolutegravir; DTG; elvitegravir resistance; integrase inhibitor; raltegravir resistance
• ISSN: 0022-1899; 1537-6613; 1537-6613
• DOI: 10.1093/infdis/jiu051

Background. The pilot phase IIb VIKING study suggested that dolutegravir (DTG), a human immunodeficiency virus (HIV) integrase inhibitor (INI), would be efficacious in INI-resistant patients at the 50 mg twice daily (BID) dose. Methods. VIKING-3 is a single-arm, open-label phase III study in which therapy-experienced adults with INI-resistant virus received DTG 50 mg BID while continuing their failing regimen (without raltegravir or elvitegravir) through day 7, after which the regimen was optimized with ≥1 fully active drug and DTG continued. The primary efficacy endpoints were the mean change from baseline in plasma HIV-1 RNA at day 8 and the proportion of subjects with HIV-1 RNA <50 c/mL at week 24. Results. Mean change in HIV-1 RNA at day 8 was -1.43 log₁₀ c/mL, and 69% of subjects achieved <50 c/mL at week 24. Multivariate analyses demonstrated a strong association between baseline DTG susceptibility and response. Response was most reduced in subjects with Q148 + ≥2 resistance-associated mutations. DTG 50 mg BID had a low (3%) discontinuation rate due to adverse events, similar to INI-naive subjects receiving DTG 50 mg once daily. Conclusions. DTG 50 mg BID-based therapy was effective in this highly treatment-experienced population with INI-resistant virus. Clinical Trials Registration. www.clinicaltrials.gov (NCT01328041) and http://www.gsk-clinicalstudywww.gsk-clinicalstudyregister.com (112574).