Dolutegravir in antiretroviral-experienced patients with raltegravir- and/or elvitegravir-resistant HIV-1: 24-week results of the phase III VIKING-3 study.
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.


BACKGROUND
www.clinicaltrials.gov (NCT01328041) and http://www.gsk-clinicalstudywww.gsk-clinicalstudyregister.com (112574).
San Raffaele Scientific Institute, Milan.
Antonella
A
Castagna
Ospedale Riuniti, Bergamo.
Franco
F
Maggiolo
Ospedale Galliera, Genova, Italy.
Giovanni
G
Penco
Central Texas Clinical Research, Austin, Texas.
David
D
Wright
Anthony Mills MD Inc, Los Angeles, California.
Anthony
A
Mills
Montefiore Medical Center, New York, New York.
Robert
R
Grossberg
Hôpital Saint-Louis, Paris.
Jean-Michel
JM
Molina
Hôpital Tenon, Paris.
Julie
J
Chas
Hôpital de L'Archet, Nice, France.
Jacques
J
Durant
Hospital Universitario Ramón y Cajal, Madrid, Spain.
Santiago
S
Moreno
Hospital de Santa Maria, Lisbon, Portugal.
Manuela
M
Doroana
GlaxoSmithKline, London, United Kingdom.
Mounir
M
Ait-Khaled
GlaxoSmithKline, Mississauga, Ontario, Canada.
Jenny
J
Huang
GlaxoSmithKline, Research Triangle Park, North Carolina.
Sherene
S
Min
GlaxoSmithKline, Research Triangle Park, North Carolina.
Ivy
I
Song
GlaxoSmithKline, Research Triangle Park, North Carolina.
Cindy
C
Vavro
GlaxoSmithKline, Research Triangle Park, North Carolina.
Garrett
G
Nichols
GlaxoSmithKline, London, United Kingdom.
Jane M
JM
Yeo
D000328:Adult; D019380:Anti-HIV Agents / Q000627:therapeutic use; D024882:Drug Resistance, Viral; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology; D015497:HIV-1 / Q000187:drug effects*; D006575:Heterocyclic Compounds, 3-Ring / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D008875:Middle Aged; D010078:Oxazines; D010865:Pilot Projects; D010879:Piperazines; D011728:Pyridones; D011760:Pyrrolidinones / Q000494:pharmacology*; D015363:Quinolones / Q000494:pharmacology*; D012367:RNA, Viral / Q000097:blood; D000068898:Raltegravir Potassium; D019562:Viral Load; D000099226:Dolutegravir
D019380:Anti-HIV Agents; D006575:Heterocyclic Compounds, 3-Ring; D010078:Oxazines; D010879:Piperazines; D011728:Pyridones; D011760:Pyrrolidinones; D015363:Quinolones; D012367:RNA, Viral; D000068898:Raltegravir Potassium; D000099226:Dolutegravir; C509700:elvitegravir
DTG; dolutegravir; elvitegravir resistance; integrase inhibitor; raltegravir resistance