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

Summary 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... Full description

Journal Title: The Lancet (British edition) 2013, Vol.382 (9893), p.700-708
Main Author: Cahn, Pedro, Dr
Other Authors: Pozniak, Anton L, MD , Mingrone, Horacio, MD , Shuldyakov, Andrey, MD , Brites, Carlos, MD , Andrade-Villanueva, Jaime F, MD , Richmond, Gary, MD , Buendia, Carlos Beltran, MD , Fourie, Jan, MD , Ramgopal, Moti, MD , Hagins, Debbie, MD , Felizarta, Franco, MD , Madruga, Jose, MD , Reuter, Tania, MD , Newman, Tamara, MD , Small, Catherine B, MD , Lombaard, John, MD , Grinsztejn, Beatriz, MD , Dorey, David, MMath , Underwood, Mark, PhD , Griffith, Sandy, PharmD , Min, Sherene, MD
Format: Electronic Article Electronic Article
Language: English
Subjects:
HIV
Quelle: Alma/SFX Local Collection
Publisher: England: Elsevier Ltd
ID: ISSN: 0140-6736
Link: https://www.ncbi.nlm.nih.gov/pubmed/23830355
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title: Dolutegravir versus raltegravir in antiretroviral-experienced, integrase-inhibitor-naive adults with HIV: week 48 results from the randomised, double-blind, non-inferiority SAILING study
format: Article
creator:
  • Cahn, Pedro, Dr
  • Pozniak, Anton L, MD
  • Mingrone, Horacio, MD
  • Shuldyakov, Andrey, MD
  • Brites, Carlos, MD
  • Andrade-Villanueva, Jaime F, MD
  • Richmond, Gary, MD
  • Buendia, Carlos Beltran, MD
  • Fourie, Jan, MD
  • Ramgopal, Moti, MD
  • Hagins, Debbie, MD
  • Felizarta, Franco, MD
  • Madruga, Jose, MD
  • Reuter, Tania, MD
  • Newman, Tamara, MD
  • Small, Catherine B, MD
  • Lombaard, John, MD
  • Grinsztejn, Beatriz, MD
  • Dorey, David, MMath
  • Underwood, Mark, PhD
  • Griffith, Sandy, PharmD
  • Min, Sherene, MD
subjects:
  • Abridged Index Medicus
  • Adult
  • Double-Blind Method
  • Drug Administration Schedule
  • Drug dosages
  • Drug Resistance, Viral
  • Drug therapy
  • Female
  • Heterocyclic Compounds, 3-Ring - administration & dosage
  • Heterocyclic Compounds, 3-Ring - adverse effects
  • HIV
  • HIV infection
  • HIV Infections - drug therapy
  • HIV Integrase Inhibitors - administration & dosage
  • HIV Integrase Inhibitors - adverse effects
  • HIV-1
  • Human immunodeficiency virus
  • Human immunodeficiency virus 1
  • Humans
  • Internal Medicine
  • Male
  • Middle Aged
  • Mutation
  • Patient safety
  • Plasma
  • Pyrrolidinones - administration & dosage
  • Pyrrolidinones - adverse effects
  • Raltegravir Potassium
  • RNA, Viral - metabolism
  • Treatment Outcome
  • Viral Load
ispartof: The Lancet (British edition), 2013, Vol.382 (9893), p.700-708
description: Summary 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 group
language: eng
source: Alma/SFX Local Collection
identifier: ISSN: 0140-6736
fulltext: fulltext
issn:
  • 0140-6736
  • 1474-547X
url: Link


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titleDolutegravir versus raltegravir in antiretroviral-experienced, integrase-inhibitor-naive adults with HIV: week 48 results from the randomised, double-blind, non-inferiority SAILING study
sourceAlma/SFX Local Collection
creatorCahn, Pedro, Dr ; Pozniak, Anton L, MD ; Mingrone, Horacio, MD ; Shuldyakov, Andrey, MD ; Brites, Carlos, MD ; Andrade-Villanueva, Jaime F, MD ; Richmond, Gary, MD ; Buendia, Carlos Beltran, MD ; Fourie, Jan, MD ; Ramgopal, Moti, MD ; Hagins, Debbie, MD ; Felizarta, Franco, MD ; Madruga, Jose, MD ; Reuter, Tania, MD ; Newman, Tamara, MD ; Small, Catherine B, MD ; Lombaard, John, MD ; Grinsztejn, Beatriz, MD ; Dorey, David, MMath ; Underwood, Mark, PhD ; Griffith, Sandy, PharmD ; Min, Sherene, MD
creatorcontribCahn, Pedro, Dr ; Pozniak, Anton L, MD ; Mingrone, Horacio, MD ; Shuldyakov, Andrey, MD ; Brites, Carlos, MD ; Andrade-Villanueva, Jaime F, MD ; Richmond, Gary, MD ; Buendia, Carlos Beltran, MD ; Fourie, Jan, MD ; Ramgopal, Moti, MD ; Hagins, Debbie, MD ; Felizarta, Franco, MD ; Madruga, Jose, MD ; Reuter, Tania, MD ; Newman, Tamara, MD ; Small, Catherine B, MD ; Lombaard, John, MD ; Grinsztejn, Beatriz, MD ; Dorey, David, MMath ; Underwood, Mark, PhD ; Griffith, Sandy, PharmD ; Min, Sherene, MD ; on behalf of the extended SAILING Study Team ; extended SAILING Study Team
descriptionSummary 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.
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subjectAbridged Index Medicus ; Adult ; Double-Blind Method ; Drug Administration Schedule ; Drug dosages ; Drug Resistance, Viral ; Drug therapy ; Female ; Heterocyclic Compounds, 3-Ring - administration & dosage ; Heterocyclic Compounds, 3-Ring - adverse effects ; HIV ; HIV infection ; HIV Infections - drug therapy ; HIV Integrase Inhibitors - administration & dosage ; HIV Integrase Inhibitors - adverse effects ; HIV-1 ; Human immunodeficiency virus ; Human immunodeficiency virus 1 ; Humans ; Internal Medicine ; Male ; Middle Aged ; Mutation ; Patient safety ; Plasma ; Pyrrolidinones - administration & dosage ; Pyrrolidinones - adverse effects ; Raltegravir Potassium ; RNA, Viral - metabolism ; Treatment Outcome ; Viral Load
ispartofThe Lancet (British edition), 2013, Vol.382 (9893), p.700-708
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1Pozniak, Anton L, MD
2Mingrone, Horacio, MD
3Shuldyakov, Andrey, MD
4Brites, Carlos, MD
5Andrade-Villanueva, Jaime F, MD
6Richmond, Gary, MD
7Buendia, Carlos Beltran, MD
8Fourie, Jan, MD
9Ramgopal, Moti, MD
10Hagins, Debbie, MD
11Felizarta, Franco, MD
12Madruga, Jose, MD
13Reuter, Tania, MD
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15Small, Catherine B, MD
16Lombaard, John, MD
17Grinsztejn, Beatriz, MD
18Dorey, David, MMath
19Underwood, Mark, PhD
20Griffith, Sandy, PharmD
21Min, Sherene, MD
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0Dolutegravir versus raltegravir in antiretroviral-experienced, integrase-inhibitor-naive adults with HIV: week 48 results from the randomised, double-blind, non-inferiority SAILING study
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descriptionSummary 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.
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titleDolutegravir versus raltegravir in antiretroviral-experienced, integrase-inhibitor-naive adults with HIV: week 48 results from the randomised, double-blind, non-inferiority SAILING study
authorCahn, Pedro, Dr ; Pozniak, Anton L, MD ; Mingrone, Horacio, MD ; Shuldyakov, Andrey, MD ; Brites, Carlos, MD ; Andrade-Villanueva, Jaime F, MD ; Richmond, Gary, MD ; Buendia, Carlos Beltran, MD ; Fourie, Jan, MD ; Ramgopal, Moti, MD ; Hagins, Debbie, MD ; Felizarta, Franco, MD ; Madruga, Jose, MD ; Reuter, Tania, MD ; Newman, Tamara, MD ; Small, Catherine B, MD ; Lombaard, John, MD ; Grinsztejn, Beatriz, MD ; Dorey, David, MMath ; Underwood, Mark, PhD ; Griffith, Sandy, PharmD ; Min, Sherene, MD
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addata
au
0Cahn, Pedro, Dr
1Pozniak, Anton L, MD
2Mingrone, Horacio, MD
3Shuldyakov, Andrey, MD
4Brites, Carlos, MD
5Andrade-Villanueva, Jaime F, MD
6Richmond, Gary, MD
7Buendia, Carlos Beltran, MD
8Fourie, Jan, MD
9Ramgopal, Moti, MD
10Hagins, Debbie, MD
11Felizarta, Franco, MD
12Madruga, Jose, MD
13Reuter, Tania, MD
14Newman, Tamara, MD
15Small, Catherine B, MD
16Lombaard, John, MD
17Grinsztejn, Beatriz, MD
18Dorey, David, MMath
19Underwood, Mark, PhD
20Griffith, Sandy, PharmD
21Min, Sherene, MD
aucorp
0on behalf of the extended SAILING Study Team
1extended SAILING Study Team
formatjournal
genrearticle
ristypeJOUR
atitleDolutegravir versus raltegravir in antiretroviral-experienced, integrase-inhibitor-naive adults with HIV: week 48 results from the randomised, double-blind, non-inferiority SAILING study
jtitleThe Lancet (British edition)
addtitleLancet
date2013
risdate2013
volume382
issue9893
spage700
epage708
pages700-708
issn0140-6736
eissn1474-547X
codenLANCAO
abstractSummary 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.
copEngland
pubElsevier Ltd
pmid23830355
doi10.1016/S0140-6736(13)61221-0