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The Lancet Infect Dis. Once-daily dolutegravir versus twice-daily raltegravir in antiretroviral-naive adults with HIV-1 infection (SPRING-2 study): 96 week results from a randomised, double-blind, non-inferiority trial
[Source: The Lancet Infectious Diseases, full page: (LINK). Abstract, edited.]
The Lancet Infectious Diseases, Early Online Publication, 25 September 2013
doi:10.1016/S1473-3099(13)70257-3
Copyright ? 2013 Elsevier Ltd All rights reserved.
Once-daily dolutegravir versus twice-daily raltegravir in antiretroviral-naive adults with HIV-1 infection (SPRING-2 study): 96 week results from a randomised, double-blind, non-inferiority trial
Original Text
Prof Fran?ois Raffi MD a, Hans Jaeger MD b, Eugenia Quiros-Roldan MD c, Prof Helmut Albrecht MD d, Elena Belonosova MD e, Prof Jose M Gatell MD f, Jean-Guy Baril MD g, Pere Domingo MD h, Clare Brennan DPT i, Steve Almond MMath j, Sherene Min MD i, on behalf of the extended SPRING-2 Study Group
Summary
Background
In the primary analysis of SPRING-2 at week 48, dolutegravir showed non-inferior efficacy to and similar tolerability to raltegravir in adults infected with HIV-1 and naive for antiretroviral treatment. We present the 96 week results.
Methods
SPRING-2 is an ongoing phase 3, randomised, double-blind, active-controlled, non-inferiority study in treatment-naive adults infected with HIV-1 that started in Oct 19, 2010. We present results for the safety cutoff date of Jan 30, 2013. Patients had to be aged 18 years or older and have HIV-1 RNA concentrations of 1000 copies per mL or more. Patients were randomly assigned (1:1) to receive either dolutegravir (50 mg once daily) or raltegravir (400 mg twice daily), plus investigator-selected tenofovir?emtricitabine or abacavir?lamivudine. Prespecified 96 week secondary endpoints included proportion of patients with HIV-1 RNA less than 50 copies per mL, CD4 cell count changes from baseline, safety, tolerability, and genotypic or phenotypic resistance. We used an intention-to-treat exposed population (received at least one dose of study drug) for the analyses. Sponsor staff were masked to treatment assignment until primary analysis at week 48; investigators, site staff, and patients were masked until week 96. This study is registered with ClinicalTrials.gov, NCT01227824.
Findings
Of 1035 patients screened, 827 were randomly assigned to study group, and 822 received at least one dose of the study drug (411 patients in each group). At week 96, 332 (81%) of 411 patients in the dolutegravir group and 314 (76%) of 411 patients in the raltegravir group had HIV-1 RNA less than 50 copies per mL (adjusted difference 4?5%, 95% CI −1?1% to 10?0%) confirming non-inferiority. Secondary analyses of efficacy such as per protocol (HIV RNA <50 copies per mL: 83% for dolutegravir and 80% for raltegravir) and treatment-related discontinuation equals failure (93% without failure for dolutegravir; 91% for raltegravir) supported non-inferiority. Virological non-response occurred less frequently in the dolutegravir group (22 [5%] patients for dolutegravir vs 43 [10%] patients for raltegravir). Median increases in CD4 cell count from baseline were similar between groups (276 cells per μL for dolutegravir and 264 cells per μL for raltegravir). Ten patients (2%) in each group discontinued because of adverse events, with few such events between weeks 48 and 96 (zero in the dolutegravir group and one in the raltegravir group). No study-related serious adverse events occurred between week 48 and week 96. At virological failure, no additional resistance to integrase inhibitors or nucleotide reverse transcriptase inhibitors was detected since week 48 or in any patient receiving dolutegravir.
Interpretation
At week 96, once-daily dolutegravir was non-inferior to twice-daily raltegravir in treatment-naive, patients with HIV-1. Once-daily dosing without requirement for a pharmacokinetic booster makes dolutegravir-based therapy an attractive treatment option for HIV-1-infected treatment-naive patients.
Funding
ViiV Healthcare.
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a Infectious and Tropical Diseases Department, Nantes University Hospital, Nantes, France; b MUC Research GmbH, Munich, Germany; c University of Brescia, Brescia, Italy; d University of South Carolina School of Medicine/Palmetto Health, Columbia, SC, USA; e Orel Regional Center for AIDS, Orel, Russia; f Hospital Cl?nic i Provincial, Barcelona, Spain; g Clinique M?dicale du Quartier Latin, Montreal, QC, Canada; h Hospital Santa Cruz y San Pablo, Barcelona, Spain; i GlaxoSmithKline, Medicine Discovery and Development, Research Triangle Park, NC, USA; j GlaxoSmithKline, Clinical Statistics, Mississauga, ON, Canada
Correspondence to: Prof Fran?ois Raffi, Infectious and Tropical Diseases Department, Nantes University Hospital, 44093 Nantes Cedex 1, France
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The Lancet Infectious Diseases, Early Online Publication, 25 September 2013
doi:10.1016/S1473-3099(13)70257-3
Copyright ? 2013 Elsevier Ltd All rights reserved.
Once-daily dolutegravir versus twice-daily raltegravir in antiretroviral-naive adults with HIV-1 infection (SPRING-2 study): 96 week results from a randomised, double-blind, non-inferiority trial
Original Text
Prof Fran?ois Raffi MD a, Hans Jaeger MD b, Eugenia Quiros-Roldan MD c, Prof Helmut Albrecht MD d, Elena Belonosova MD e, Prof Jose M Gatell MD f, Jean-Guy Baril MD g, Pere Domingo MD h, Clare Brennan DPT i, Steve Almond MMath j, Sherene Min MD i, on behalf of the extended SPRING-2 Study Group
Summary
Background
In the primary analysis of SPRING-2 at week 48, dolutegravir showed non-inferior efficacy to and similar tolerability to raltegravir in adults infected with HIV-1 and naive for antiretroviral treatment. We present the 96 week results.
Methods
SPRING-2 is an ongoing phase 3, randomised, double-blind, active-controlled, non-inferiority study in treatment-naive adults infected with HIV-1 that started in Oct 19, 2010. We present results for the safety cutoff date of Jan 30, 2013. Patients had to be aged 18 years or older and have HIV-1 RNA concentrations of 1000 copies per mL or more. Patients were randomly assigned (1:1) to receive either dolutegravir (50 mg once daily) or raltegravir (400 mg twice daily), plus investigator-selected tenofovir?emtricitabine or abacavir?lamivudine. Prespecified 96 week secondary endpoints included proportion of patients with HIV-1 RNA less than 50 copies per mL, CD4 cell count changes from baseline, safety, tolerability, and genotypic or phenotypic resistance. We used an intention-to-treat exposed population (received at least one dose of study drug) for the analyses. Sponsor staff were masked to treatment assignment until primary analysis at week 48; investigators, site staff, and patients were masked until week 96. This study is registered with ClinicalTrials.gov, NCT01227824.
Findings
Of 1035 patients screened, 827 were randomly assigned to study group, and 822 received at least one dose of the study drug (411 patients in each group). At week 96, 332 (81%) of 411 patients in the dolutegravir group and 314 (76%) of 411 patients in the raltegravir group had HIV-1 RNA less than 50 copies per mL (adjusted difference 4?5%, 95% CI −1?1% to 10?0%) confirming non-inferiority. Secondary analyses of efficacy such as per protocol (HIV RNA <50 copies per mL: 83% for dolutegravir and 80% for raltegravir) and treatment-related discontinuation equals failure (93% without failure for dolutegravir; 91% for raltegravir) supported non-inferiority. Virological non-response occurred less frequently in the dolutegravir group (22 [5%] patients for dolutegravir vs 43 [10%] patients for raltegravir). Median increases in CD4 cell count from baseline were similar between groups (276 cells per μL for dolutegravir and 264 cells per μL for raltegravir). Ten patients (2%) in each group discontinued because of adverse events, with few such events between weeks 48 and 96 (zero in the dolutegravir group and one in the raltegravir group). No study-related serious adverse events occurred between week 48 and week 96. At virological failure, no additional resistance to integrase inhibitors or nucleotide reverse transcriptase inhibitors was detected since week 48 or in any patient receiving dolutegravir.
Interpretation
At week 96, once-daily dolutegravir was non-inferior to twice-daily raltegravir in treatment-naive, patients with HIV-1. Once-daily dosing without requirement for a pharmacokinetic booster makes dolutegravir-based therapy an attractive treatment option for HIV-1-infected treatment-naive patients.
Funding
ViiV Healthcare.
_____
a Infectious and Tropical Diseases Department, Nantes University Hospital, Nantes, France; b MUC Research GmbH, Munich, Germany; c University of Brescia, Brescia, Italy; d University of South Carolina School of Medicine/Palmetto Health, Columbia, SC, USA; e Orel Regional Center for AIDS, Orel, Russia; f Hospital Cl?nic i Provincial, Barcelona, Spain; g Clinique M?dicale du Quartier Latin, Montreal, QC, Canada; h Hospital Santa Cruz y San Pablo, Barcelona, Spain; i GlaxoSmithKline, Medicine Discovery and Development, Research Triangle Park, NC, USA; j GlaxoSmithKline, Clinical Statistics, Mississauga, ON, Canada
Correspondence to: Prof Fran?ois Raffi, Infectious and Tropical Diseases Department, Nantes University Hospital, 44093 Nantes Cedex 1, France
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