Dolutegravir plus Abacavir–Lamivudine for the Treatment of HIV-1 Infection

Walmsley, Sharon; Antela, Antonio; Clumeck, Nathan; Duiculescu, Dan; Eberhard, Andrea; Gutiérrez, Félix; Hocqueloux, Laurent; Maggiolo, Franco; Sandkovsky, Uriel; Granier, Catherine; Pappa, Keith A.; Wynne, Brian; Min, Sherene; Nichols, Garrett

doi:10.1056/nejmoa1215541

Cited by 771 publications

(784 citation statements)

References 27 publications

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“…Recent analyses have revealed that mortality rates for HIV-1-infected persons have become close to that of general population and that the recent first-line cART with integrase inhibitors or boosted protease inhibitor (PI)-based regimens has made the development of HIV-1 resistance significantly less likely over an extended period of time (5,6). A recent study reported that 20-yearold HIV-1-infected individuals who started cART between 2003 and 2005 are expected to live an additional 49 years, to the age of 69 (7,8).…”

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confidence: 99%

C-5-Modified Tetrahydropyrano-Tetrahydofuran-Derived Protease Inhibitors (PIs) Exert Potent Inhibition of the Replication of HIV-1 Variants Highly Resistant to Various PIs, including Darunavir

Aoki

Hayashi

Yedidi

et al. 2016

J Virol

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We identified three nonpeptidic HIV-1 protease inhibitors (PIs), GRL-015, -085, and -097, containing tetrahydropyrano-tetrahydrofuran (Tp-THF) with a C-5 hydroxyl. The three compounds were potent against a wild-type laboratory HIV-1 strain (HIV-1 WT ), with 50% effective concentrations (EC 50 s) of 3.0 to 49 nM, and exhibited minimal cytotoxicity, with 50% cytotoxic concentrations (CC 50 ) for GRL-015, -085, and -097 of 80, >100, and >100 M,

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confidence: 99%

C-5-Modified Tetrahydropyrano-Tetrahydofuran-Derived Protease Inhibitors (PIs) Exert Potent Inhibition of the Replication of HIV-1 Variants Highly Resistant to Various PIs, including Darunavir

Aoki

Hayashi

Yedidi

et al. 2016

J Virol

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“…A remarkable strength of this study is the long follow-up period in comparison with clinical trials and other prospective cohort studies published to date [6,7,10,24]. Of interest, the median time to CRDRF event was 3.6 years, which is much longer than most follow-up periods in other studies.…”

Section: Discussionmentioning

confidence: 81%

Long-term comparative and prospective cohort study of renal function in patients with HIV infection treated with tenofovir disoproxil fumarate

Calle¹,

Pulido²,

Sánchez-Conde³

et al. 2017

HIV & AIDS Review

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“…23 In a separate randomised trial (SINGLE), which compared dolutegravir (DTG) + ABC + 3TC and EFV + FTC + TDF, no subjects in the DTG + ABC + 3TC group had detectable antiviral resistance whereas one TDF-associated mutation and four EFV-associated mutations were detected in the EFV-TDF-FTC group. 24 BMS-986001 was generally well tolerated through Week 48. Some Grade 2-4-related AEs were more frequently reported in the BMS-986001 arms compared with TDF, however no dose-related trends for the BMS-986001 arms were apparent.…”

Section: Discussionmentioning

confidence: 96%

Efficacy, safety, bone and metabolic effects of HIV nucleoside reverse transcriptase inhibitor BMS-986001 (AI467003): a phase 2b randomised, controlled, partly blinded trial

Gupta

McComsey

Lombaard³

et al. 2016

The Lancet HIV

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MethodsAI467003 was a Phase 2b, randomised, active-controlled, blinded-to-BMS-986001 dose trial.HIV-1-infected adults with plasma HIV-1 RNA greater than 5000 copies per mL and CD4+ T-cell counts greater than 200 cells/mm 3 were randomised 2:2:2:3 to three BMS-986001 arms (100, 200 or 400 mg once daily), or reference arm (TDF 300 mg once daily), each with efavirenz (600 mg once daily) and lamivudine (300 mg once daily). Both subjects and investigators remained blinded to BMS-986001 dose, but not allocation, through Week 48. Proportion of subjects with plasma HIV-1 RNA less than 50 copies per mL and safety (serious adverse events [SAEs] and AEs leading to discontinuation) through Week 24 were primary endpoints. Resistance analysis was a secondary endpoint, and additional safety parameters were exploratory endpoints.AI467003 is registered with ClinicalTrials.gov (NCT01489046). FindingsA total of 757 subjects were assessed for eligibility and 301 randomised. Randomised subjects were assigned to receive either BMS-986001 (n=67 for the 100 mg once-daily group, n=67 for the 200 mg once-daily group, n=66 for the 400 mg once-daily group) or TDF (n=101 In a Phase 2a, dose-escalating, monotherapy study conducted for 10 days in treatment-experienced, HIV-1-infected, subjects who were not exposed to any antiretroviral treatment in the previous 3months, BMS-986001 demonstrated a median decrease in HIV-1 RNA from baseline of at least 1 log10 copies per mL for all doses. 19 These findings were used to support the design of this dosefinding Phase 2b study, which assessed the efficacy and safety of three doses of BMS-986001 (100, 200, and 400 mg once daily) versus tenofovir disoproxil fumarate (TDF 300 mg once daily), when coadministered with efavirenz (EFV 600 mg once daily) and lamivudine (3TC 300 mg once daily) in treatment-naïve, HIV-1-infected subjects. A detailed assessment of bone, renal, metabolic and mitochondrial parameters was performed to assess the safety of BMS-986001. 6 METHODS Study designAI467003 was a Phase 2b, randomised, active-controlled, blinded-to-BMS-986001 dose trial carried out at 47 sites across South America, North America, South Africa, Australia, Asia, and Europe.This study was conducted in accordance with Good Clinical Practice (GCP), as defined by the ParticipantsEligible subjects were treatment-naïve (defined as no current or previous exposure to an antiretroviral drug for more than 1 week), HIV-1-infected adults aged at least 18 years with plasma HIV-1 RNA greater than 5,000 copies per mL and CD4+ T-cell counts greater than 200 cells/mm 3 at screening.Exclusion criteria included a history of phenotypic and/or genotypic drug resistance testing showing resistance to EFV, TDF, or 3TC, presence of hepatitis B surface antigen, hepatitis C virus antibody or RNA, history of abnormal liver transaminases (defined as greater than three times the upper limit of normal) at screening, and creatinine clearance less than 60 mL/min at screening. All subjects provided written informed consent in agreement wi...

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Dolutegravir plus Abacavir–Lamivudine for the Treatment of HIV-1 Infection

Cited by 771 publications

References 27 publications

C-5-Modified Tetrahydropyrano-Tetrahydofuran-Derived Protease Inhibitors (PIs) Exert Potent Inhibition of the Replication of HIV-1 Variants Highly Resistant to Various PIs, including Darunavir

C-5-Modified Tetrahydropyrano-Tetrahydofuran-Derived Protease Inhibitors (PIs) Exert Potent Inhibition of the Replication of HIV-1 Variants Highly Resistant to Various PIs, including Darunavir

Long-term comparative and prospective cohort study of renal function in patients with HIV infection treated with tenofovir disoproxil fumarate

Efficacy, safety, bone and metabolic effects of HIV nucleoside reverse transcriptase inhibitor BMS-986001 (AI467003): a phase 2b randomised, controlled, partly blinded trial

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