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Lancet. 2013 Aug 24;382(9893):700-8. doi: 10.1016/S0140-6736(13)61221-0. Epub 2013 Jul 3.

Dolutegravir versus raltegravir in antiretroviral-experienced, integrase-inhibitor-naive adults with HIV: week 48 results from the randomised, double-blind, non-inferiority SAILING study.

Collaborators (163)

Saud AE, Ajana F, Akil B, Villanueva JF, Anstead GM, Bánhegyi D, Barros C, Bartczak JC, Belloso WH, Buendia CJ, Benetucci JA, Blick G, Bloch M, Martínez VB, Brar I, Alves CR, Burack JH, Cahn PE, Sánchez AC, Caseiro MM, Casey KK, Cassetti LI, Iglesia MA, Chernova OE, Sala BC, Clumeck N, Conway B, De Andrade Neto JL, Gil Ide L, De Truchis P, Comerma ED, Delfraissy JF, Den Hollander JG, Di Perri G, Diaz RS, Duiculescu D, Elliott JH, Eron JJ Jr, Feinberg J, Felizarta FA, File TM Jr, Florence E, Cid JF, Fourie J, Galindo MJ, Gargalianos-Kakolyris P, Gathe JC Jr, Ghosn J, Gogos C, García JG, Hernández-Mora MG, Gori A, Goulston C, Granados-Reyes ER, Grinsztejn BG, Gulick PG, Gupta SK, Hagins DP, Hardy WD, Hay P, Henry WK, Hicks CB, Hodder SL, Horton J, Huhn G, Jefferson TT, Johnson MA, Johnson PC, Katlama C, Kegg S, Khafizov KM, Khanlou H, Khoo SH, Kozal MJ, Kozyrev OA, Kulagin VV, Kumar PN, Lasso M, Latiff G, Lazzarin A, Legrand JC, Lin HH, Lin YH, Logue KJ, Lombaard JJ, Lupo SH, Madruga JV, Masia Mdel M, McCurdy LH, McDonald CK, Meier JL, Mikhaylov EV, Mildvan D, Mingrone H, Molina JM, Moshkovich GF, Mosqueda-Gómez JL, Moutschen M, Murphy MD, Nagimova FI, Nahass RG, Newman TN, Newman-Whitlow CL, Nguyen TC, O'Keefe JP, Osiyemi OO, Paparizos V, Parks DA, Perez C, Pialoux G, Piga S, Poizot-Martin I, Pokrovsky VV, Pronin A, Quertainmont Y, Rakhmanova AG, Ramgopal MN, Reuter TQ, Ribera E, Richmond GJ, Robbins WJ, Baño JR, Rodriguez JE, Rosas-Dossetti MM, Ruane PJ, Rugina S, Rusconi S, Ryamova EP, Saag MS, Samuel R, Sandkovsky US, Scarsella AJ, Schneider S, Schrader SR, Scribner AR, Shalit P, Shuldyakov AA, Siraj DS, Slim J, Sloan LM, Smaill FM, Small CB, Sonin DB, Streinu-Cercel A, Tashima KT, Tebas P, Teicher E, Tremblay C, Tsai HC, Tupinambas U, Vanig TJ, Méndez FJ, De Miguel MÁ, Wang JH, Ward DJ, Warner DA, Wheeler DA, Wilkins EG, Wolff MJ, Wong WW, Yazdanpanah Y, Yeni GP, Zingman BS.

Author information

1
Fundacion Huesped, Buenos Aires, Argentina. pcahn@huesped.org.ar

Erratum in

  • Lancet. 2014 Jan 4;383(9911):30.

Abstract

BACKGROUND:

Dolutegravir (GSK1349572), a once-daily HIV integrase inhibitor, has shown potent antiviral response and a favourable safety profile. We evaluated safety, efficacy, and emergent resistance in antiretroviral-experienced, integrase-inhibitor-naive adults with HIV-1 with at least two-class drug resistance.

METHODS:

ING111762 (SAILING) is a 48 week, phase 3, randomised, double-blind, active-controlled, non-inferiority study that began in October, 2010. Eligible patients had two consecutive plasma HIV-1 RNA assessments of 400 copies per mL or higher (unless >1000 copies per mL at screening), resistance to two or more classes of antiretroviral drugs, and had one to two fully active drugs for background therapy. Participants were randomly assigned (1:1) to once-daily dolutegravir 50 mg or twice-daily raltegravir 400 mg, with investigator-selected background therapy. Matching placebo was given, and study sites were masked to treatment assignment. The primary endpoint was the proportion of patients with plasma HIV-1 RNA less than 50 copies per mL at week 48, evaluated in all participants randomly assigned to treatment groups who received at least one dose of study drug, excluding participants at one site with violations of good clinical practice. Non-inferiority was prespecified with a 12% margin; if non-inferiority was established, then superiority would be tested per a prespecified sequential testing procedure. A key prespecified secondary endpoint was the proportion of patients with treatment-emergent integrase-inhibitor resistance. The trial is registered at ClinicalTrials.gov, NCT01231516.

FINDINGS:

Analysis included 715 patients (354 dolutegravir; 361 raltegravir). At week 48, 251 (71%) patients on dolutegravir had HIV-1 RNA less than 50 copies per mL versus 230 (64%) patients on raltegravir (adjusted difference 7·4%, 95% CI 0·7 to 14·2); superiority of dolutegravir versus raltegravir was then concluded (p=0·03). Significantly fewer patients had virological failure with treatment-emergent integrase-inhibitor resistance on dolutegravir (four vs 17 patients; adjusted difference -3·7%, 95% CI -6·1 to -1·2; p=0·003). Adverse event frequencies were similar across groups; the most commonly reported events for dolutegravir versus raltegravir were diarrhoea (71 [20%] vs 64 [18%] patients), upper respiratory tract infection (38 [11%] vs 29 [8%]), and headache (33 [9%] vs 31 [9%]). Safety events leading to discontinuation were infrequent in both groups (nine [3%] dolutegravir, 14 [4%] raltegravir).

INTERPRETATION:

Once-daily dolutegravir, in combination with up to two other antiretroviral drugs, is well tolerated with greater virological effect compared with twice-daily raltegravir in this treatment-experienced patient group.

FUNDING:

ViiV Healthcare.

PMID:
23830355
DOI:
10.1016/S0140-6736(13)61221-0
[Indexed for MEDLINE]
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