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Anthony Mills - One of the best experts on this subject based on the ideXlab platform.

  • a week 48 randomized phase 3 trial of darunavir cobicistat Emtricitabine tenofovir alafenamide in treatment naive hiv 1 patients
    AIDS, 2018
    Co-Authors: Joseph J. Eron, Erika Van Landuyt, Joel E Gallant, Jacques Reynes, Andrea Antinori, Chloe Orkin, Eugenia Negredo, Jean Michel Molina, Anthony Mills, Erkki Lathouwers
    Abstract:

    Objectives:To investigate efficacy and safety of a single-tablet regimen of darunavir/cobicistat/Emtricitabine/tenofovir alafenamide (D/C/F/TAF) 800/150/200/10 mg vs. darunavir/cobicistat plus Emtricitabine/tenofovir disoproxyl fumarate (TDF) (control) in antiretroviral-treatment-naive, HIV-1-infect

  • A week-48 randomized phase-3 trial of darunavir/cobicistat/Emtricitabine/tenofovir alafenamide in treatment-naive HIV-1 patients
    AIDS, 2018
    Co-Authors: Joseph J. Eron, Jacques Reynes, Andrea Antinori, Chloe Orkin, Eugenia Negredo, Jean Michel Molina, Anthony Mills, Joel Gallant, Erika Van Landuyt, Erkki Lathouwers
    Abstract:

    OBJECTIVES: To investigate efficacy and safety of a single-tablet regimen of darunavir/cobicistat/Emtricitabine/tenofovir alafenamide (D/C/F/TAF) 800/150/200/10 mg vs. darunavir/cobicistat plus Emtricitabine/tenofovir disoproxyl fumarate (TDF) (control) in antiretroviral-treatment-naive, HIV-1-infected adults. DESIGN: Phase-3, randomized, active-controlled, double-blind, international, multicenter, noninferiority study (NCT02431247). METHODS: Seven hundred and twenty-five participants were randomized (1 : 1) to D/C/F/TAF (362) or control (363). The primary objective was to demonstrate noninferiority of D/C/F/TAF vs. control for percentage viral load less than 50 copies/ml (FDA-snapshot analysis) at 48 weeks (10% margin). RESULTS: At week 48, D/C/F/TAF was noninferior to control (91.4 vs. 88.4% achieved viral load

  • switching to fixed dose bictegravir Emtricitabine and tenofovir alafenamide from dolutegravir plus abacavir and lamivudine in virologically suppressed adults with hiv 1 48 week results of a randomised double blind multicentre active controlled phase
    The Lancet HIV, 2018
    Co-Authors: Jean Michel Molina, Luis F Lopezcortes, Peter Ruane, Daniel Podzamczer, Cynthia Brinson, Anthony Mills, Douglas J. Ward, Indira Brar, Joseph Custodio
    Abstract:

    Summary Background Bictegravir, co-formulated with Emtricitabine and tenofovir alafenamide, has shown good efficacy and tolerability, and similar bone, renal, and lipid profiles to dolutegravir, abacavir, and lamivudine, in treatment-naive adults with HIV-1 infection, without development of treatment-emergent resistance. Here, we report 48-week results of a phase 3 study investigating switching to bictegravir, Emtricitabine, and tenofovir alafenamide from dolutegravir, abacavir, and lamivudine in virologically suppressed adults with HIV-1 infection. Methods In this multicentre, randomised, double-blind, active-controlled, non-inferiority, phase 3 trial, HIV-1-infected adults were enrolled at 96 outpatient centres in nine countries. Eligible participants were aged 18 years or older and on a regimen of 50 mg dolutegravir, 600 mg abacavir, and 300 mg lamivudine (fixed-dose combination or multi-tablet regimen); had an estimated glomerular filtration rate of 50 mL/min or higher; and had been virologically suppressed (plasma HIV-1 RNA Findings Between Nov 11, 2015, and July 6, 2016, 567 participants were randomly assigned and 563 were treated (282 received bictegravir, Emtricitabine, and tenofovir alafenamide, and 281 received dolutegravir, abacavir, and lamivudine). Switching to the bictegravir regimen was non-inferior to remaining on dolutegravir, abacavir, and lamivudine for the primary outcome: three (1%) of 282 in the bictegravir group had HIV-1 RNA of 50 copies per mL or higher at week 48 versus one ( Interpretation The fixed-dose combination of bictegravir, Emtricitabine, and tenofovir alafenamide might provide a safe and efficacious option for ongoing treatment of HIV-1 infection. Funding Gilead Sciences.

  • bictegravir Emtricitabine and tenofovir alafenamide versus dolutegravir abacavir and lamivudine for initial treatment of hiv 1 infection gs us 380 1489 a double blind multicentre phase 3 randomised controlled non inferiority trial
    The Lancet, 2017
    Co-Authors: Joel E Gallant, Pablo Tebas, Chloe Orkin, Daniel Podzamczer, Anthony Mills, Adriano Lazzarin, Eric S. Daar, Pierre Marie Girard, Indira Brar, David A Wohl
    Abstract:

    Summary Background Integrase strand transfer inhibitors (INSTIs) are recommended components of initial antiretroviral therapy with two nucleoside reverse transcriptase inhibitors. Bictegravir is a novel, potent INSTI with a high in-vitro barrier to resistance and low potential as a perpetrator or victim of clinically relevant drug–drug interactions. We aimed to assess the efficacy and safety of bictegravir coformulated with Emtricitabine and tenofovir alafenamide as a fixed-dose combination versus coformulated dolutegravir, abacavir, and lamivudine. Methods We did this double-blind, multicentre, active-controlled, randomised controlled non-inferiority trial at 122 outpatient centres in nine countries in Europe, Latin America, and North America. We enrolled HIV-1 infected adults (aged ≥18 years) who were previously untreated (HIV-1 RNA ≥500 copies per mL); HLA-B*5701 -negative; had no hepatitis B virus infection; screening genotypes showing sensitivity to Emtricitabine, tenofovir, lamivudine, and abacavir; and an estimated glomerular filtration rate of 50 mL/min or more. Participants were randomly assigned (1:1), via a computer-generated allocation sequence (block size of four), to receive coformulated bictegravir 50 mg, Emtricitabine 200 mg, and tenofovir alafenamide 25 mg or coformulated dolutegravir 50 mg, abacavir 600 mg, and lamivudine 300 mg, with matching placebo, once daily for 144 weeks. Randomisation was stratified by HIV-1 RNA (≤100 000 copies per mL, >100 000 to ≤400 000 copies per mL, or >400 000 copies per mL), CD4 count ( Findings Between Nov 13, 2015, and July 14, 2016, we randomly assigned 631 participants to receive coformulated bictegravir, Emtricitabine, and tenofovir alafenamide (n=316) or coformulated dolutegravir, abacavir, and lamivudine (n=315), of whom 314 and 315 patients, respectively, received at least one dose of study drug. At week 48, HIV-1 RNA less than 50 copies per mL was achieved in 92·4% of patients (n=290 of 314) in the bictegravir, Emtricitabine, and tenofovir alafenamide group and 93·0% of patients (n=293 of 315) in the dolutegravir, abacavir, and lamivudine group (difference −0·6%, 95·002% CI −4·8 to 3·6; p=0·78), demonstrating non-inferiority of bictegravir, Emtricitabine, and tenofovir alafenamide to dolutegravir, abacavir, and lamivudine. No individual developed treatment-emergent resistance to any study drug. Incidence and severity of adverse events was mostly similar between groups except for nausea, which occurred less frequently in patients given bictegravir, Emtricitabine, and tenofovir alafenamide than in those given dolutegravir, abacavir, and lamivudine (10% [n=32] vs 23% [n=72]; p vs 40% [n=127]), the difference being driven by a higher incidence of drug-related nausea in the dolutegravir, abacavir, and lamivudine group (5% [n=17] vs 17% [n=55]; p Interpretation At 48 weeks, coformulated bictegravir, Emtricitabine, and tenofovir alafenamide achieved virological suppression in 92% of previously untreated adults and was non-inferior to coformulated dolutegravir, abacavir, and lamivudine, with no treatment-emergent resistance. Bictegravir, Emtricitabine, and tenofovir alafenamide was safe and well tolerated with better gastrointestinal tolerability than dolutegravir, abacavir, and lamivudine. Because coformulated bictegravir, Emtricitabine, and tenofovir alafenamide does not require HLA B*5701 testing and provides guideline-recommended treatment for individuals co-infected with HIV and hepatitis B, this regimen might lend itself to rapid or same-day initiation of therapy in the clinical setting. Funding Gilead Sciences.

  • switching from tenofovir disoproxil fumarate to tenofovir alafenamide coformulated with rilpivirine and Emtricitabine in virally suppressed adults with hiv 1 infection a randomised double blind multicentre phase 3b non inferiority study
    The Lancet HIV, 2017
    Co-Authors: Chloe Orkin, Gordon Crofoot, Peter Ruane, E Dejesus, Anthony Mills, Moti Ramgopal, Anthony Lamarca, Bernard Vandercam, Joseph De Wet, Jurgen K Rockstroh
    Abstract:

    Summary Background Tenofovir alafenamide, a tenofovir prodrug, results in 90% lower tenofovir plasma concentrations than does tenofovir disproxil fumarate, thereby minimising bone and renal risks. We investigated the efficacy, safety, and tolerability of switching to a single-tablet regimen containing rilpivirine, Emtricitabine, and tenofovir alafenamide compared with remaining on rilpivirine, Emtricitabine, and tenofovir disoproxil fumarate. Methods In this randomised, double-blind, multicentre, placebo-controlled, non-inferiority trial, HIV-1-infected adults were screened and enrolled at 119 hospitals in 11 countries in North America and Europe. Participants were virally suppressed (HIV-1 RNA Findings Between Jan 26, 2015, and Aug 25, 2015, 630 participants were randomised (316 to the tenofovir alafenamide group and 314 to the tenofovir disoproxil fumarate group). At week 48, 296 (94%) of 316 participants on tenofovir alafenamide and 294 (94%) of 313 on tenofovir disoproxil fumarate had maintained less than 50 copies per mL HIV-1 RNA (difference −0·3%, 95·001% CI −4·2 to 3·7), showing non-inferiority of tenofovir alafenamide to tenofovir disoproxil fumarate. Numbers of adverse events were similar between groups. 20 (6%) of 316 participants had study-drug related adverse events in the tenofovir alafenamide group compared with 37 (12%) of 314 in the tenofovir disoproxil fumarate group; none of these were serious. Interpretation Switching to rilpivirine, Emtricitabine, and tenofovir alafenamide was non-inferior to continuing rilpivirine, Emtricitabine, tenofovir disoproxil fumarate in maintaining viral suppression and was well tolerated at 48 weeks. These findings support guidelines recommending tenofovir alafenamide-based regimens, including coformulation with rilpivirine and Emtricitabine, as initial and ongoing treatment for HIV-1 infection. Funding Gilead Sciences.

E Dejesus - One of the best experts on this subject based on the ideXlab platform.

  • Emtricitabine and tenofovir alafenamide vs Emtricitabine and tenofovir disoproxil fumarate for hiv pre exposure prophylaxis discover primary results from a randomised double blind multicentre active controlled phase 3 non inferiority trial
    The Lancet, 2020
    Co-Authors: E Dejesus, Jean Michel Molina, Melanie A Thompson, Peter L. Anderson, Kenneth H Mayer, Karam Mounzer, Joss J De Wet, Heiko Jessen, Robert M Grant
    Abstract:

    Summary Background Tenofovir alafenamide shows high antiviral efficacy and improved renal and bone safety compared with tenofovir disoproxil fumarate when used for HIV treatment. Here, we report primary results from a blinded phase 3 study evaluating the efficacy and safety of pre-exposure prophylaxis (PrEP) with Emtricitabine and tenofovir alafenamide versus Emtricitabine and tenofovir disoproxil fumarate for HIV prevention. Methods This study is an ongoing, randomised, double-blind, multicentre, active-controlled, phase 3, non-inferiority trial done at 94 community, public health, and hospital-associated clinics located in regions of Europe and North America, where there is a high incidence of HIV or prevalence of people living with HIV, or both. We enrolled adult cisgender men who have sex with men and transgender women who have sex with men, both with a high risk of acquiring HIV on the basis of their self-reported sexual behaviour in the past 12 weeks or their recent history (within 24 weeks of enrolment) of bacterial sexually transmitted infections. Participants with current or previous use of PrEP with Emtricitabine and tenofovir disoproxil fumarate were not excluded. We used a computer-generated random allocation sequence to randomly assign (1:1) participants to receive either Emtricitabine (200 mg) and tenofovir alafenamide (25 mg) tablets daily, with matched placebo tablets (Emtricitabine and tenofovir alafenamide group), or Emtricitabine (200 mg) and tenofovir disoproxil fumarate (300 mg) tablets daily, with matched placebo tablets (Emtricitabine and tenofovir disoproxil fumarate group). As such, all participants were given two tablets. The trial sponsor, investigators, participants, and the study staff who provided the study drugs, assessed the outcomes, and collected the data were masked to group assignment. The primary efficacy outcome was incident HIV infection, which was assessed when all participants had completed 48 weeks of follow-up and half of all participants had completed 96 weeks of follow-up. This full analysis set included all randomly assigned participants who had received at least one dose of the assigned study drug and had at least one post-baseline HIV test. Non-inferiority of Emtricitabine and tenofovir alafenamide to Emtricitabine and tenofovir disoproxil fumarate was established if the upper bound of the 95·003% CI of the HIV incidence rate ratio (IRR) was less than the prespecified non-inferiority margin of 1·62. We prespecified six secondary bone mineral density and renal biomarker safety endpoints to evaluate using the safety analysis set. This analysis set included all randomly assigned participants who had received at least one dose of the assigned study drug. This trial is registered with ClinicalTrials.gov , NCT02842086 , and is no longer recruiting. Findings Between Sept 13, 2016, and June 30, 2017, 5387 (92%) of 5857 participants were randomly assigned and received Emtricitabine and tenofovir alafenamide (n=2694) or Emtricitabine and tenofovir disoproxil fumarate (n=2693). At the time of the primary efficacy analysis (ie, when all participants had completed 48 weeks and 50% had completed 96 weeks) Emtricitabine and tenofovir alafenamide was non-inferior to Emtricitabine and tenofovir disoproxil fumarate for HIV prevention, as the upper limit of the 95% CI of the IRR, was less than the prespecified non-inferiority margin of 1·62 (IRR 0·47 [95% CI 0·19–1·15]). After 8756 person-years of follow-up, 22 participants were diagnosed with HIV, seven participants in the Emtricitabine and tenofovir alafenamide group (0·16 infections per 100 person-years [95% CI 0·06–0·33]), and 15 participants in the Emtricitabine and tenofovir disoproxil fumarate group (0·34 infections per 100 person-years [0·19–0·56]). Both regimens were well tolerated, with a low number of participants reporting adverse events that led to discontinuation of the study drug (36 [1%] of 2694 participants in the Emtricitabine and tenofovir alafenamide group vs 49 [2%] of 2693 participants in the Emtricitabine and tenofovir disoproxil fumarate group). Emtricitabine and tenofovir alafenamide was superior to Emtricitabine and tenofovir disoproxil fumarate in all six prespecified bone mineral density and renal biomarker safety endpoints. Interpretation Daily Emtricitabine and tenofovir alafenamide shows non-inferior efficacy to daily Emtricitabine and tenofovir disoproxil fumarate for HIV prevention, and the number of adverse events for both regimens was low. Emtricitabine and tenofovir alafenamide had more favourable effects on bone mineral density and biomarkers of renal safety than Emtricitabine and tenofovir disoproxil fumarate. Funding Gilead Sciences.

  • fixed dose combination bictegravir Emtricitabine and tenofovir alafenamide versus dolutegravir containing regimens for initial treatment of hiv 1 infection week 144 results from two randomised double blind multicentre phase 3 non inferiority trials
    The Lancet HIV, 2020
    Co-Authors: Chloe Orkin, Hj Stellbrink, Franco Maggiolo, E Dejesus, Carlos Martorell, David A Wohl, Jeffrey L Stephens, Samir K. Gupta, Jose R. Arribas, Melanie A Thompson
    Abstract:

    Summary Background In the primary week-48 analyses of two phase 3 studies, coformulated bictegravir, Emtricitabine, and tenofovir alafenamide was non-inferior to a dolutegravir-containing regimen in treatment-naive people with HIV. We report week-144 efficacy and safety results from these studies. Methods We did two double-blind, active-controlled studies (now in open-label extension phase). Study 1 randomly assigned (1:1) HLA-B*5701-negative adults without hepatitis B virus co-infection to receive coformulated bictegravir 50 mg, Emtricitabine 200 mg, and tenofovir alafenamide 25 mg, or coformulated dolutegravir 50 mg, abacavir 600 mg, and lamivudine 300 mg once daily. Study 2 randomly assigned (1:1) adults to bictegravir, Emtricitabine, and tenofovir alafenamide, or dolutegravir 50 mg given with coformulated Emtricitabine 200 mg and tenofovir alafenamide 25 mg. We previously reported non-inferiority at the primary endpoint. Here, we report the week-144 secondary outcome of proportion of participants with plasma HIV-1 RNA less than 50 copies per mL at week 144, by US Food and Drug Administration Snapshot algorithm, analysed in the same manner. These studies were registered with ClinicalTrials.gov , NCT02607930 and NCT02607956 . Findings 629 participants were randomly assigned and treated in study 1 (314 to bictegravir, Emtricitabine, and tenofovir alafenamide, and 315 to dolutegravir, abacavir, and lamivudine) and 645 in study 2 (327 to bictegravir, Emtricitabine, and tenofovir alafenamide, 325 to dolutegravir, Emtricitabine, tenofovir alafenamide). At week 144, bictegravir, Emtricitabine, and tenofovir alafenamide was non-inferior to both dolutegravir-containing regimens for efficacy. In study 1, 256 (82%) of 314 participants had plasma HIV-1 RNA less than 50 copies per mL in the bictegravir, Emtricitabine, and tenofovir alafenamide group and 265 (84%) of 315 in the dolutegravir, abacavir, and lamivudine group (difference −2·6%, 95% CI −8·5 to 3·4). In study 2, 262 (82%) of 320 participants had plasma HIV-1 RNA less than 50 copies per mL in the bictegravir, Emtricitabine, and tenofovir alafenamide group and 273 (84%) of 325 in the dolutegravir, Emtricitabine, and tenofovir alafenamide group (difference −1·9%, −7·8 to 3·9). In both studies, no participant had treatment-emergent resistance to study drugs up to week 144. All treatment regimens were well tolerated with additional exposure. Adverse events that led to study drug discontinuation were reported for no participants in the bictegravir, Emtricitabine, and tenofovir alafenamide group versus five (2%) of 315 in the dolutegravir, abacavir, and lamivudine group (study 1), and six (2%) of 320 in the bictegravir, Emtricitabine, and tenofovir alafenamide versus six (2%) of 325 in the dolutegravir, Emtricitabine, and tenofovir alafenamide group (study 2). In study 1, statistically significant differences were observed in median changes from baseline in fasting total cholesterol (14 mg/dL vs 10 mg/dL; p=0·034), direct LDL (21 mg/dL vs 14 mg/dL; p=0·004), and total cholesterol to HDL ratio (−0·1 vs −0·3; p=0·007) at week 144; no differences were observed between groups in study 2. Weight gain was seen across all treatment groups in both studies, with no differences in median changes from baseline in weight at week 144 for either study. Interpretation These long-term data support the use of bictegravir, Emtricitabine, and tenofovir alafenamide as a safe, well tolerated, and durable treatment for people with HIV, with no emergent resistance. Funding Gilead Sciences.

  • tenofovir alafenamide plus Emtricitabine versus abacavir plus lamivudine for treatment of virologically suppressed hiv 1 infected adults a randomised double blind active controlled non inferiority phase 3 trial
    The Lancet HIV, 2018
    Co-Authors: Alan Winston, Frank A Post, Vicente Estrada, Paula Peyrani, Francois Raffi, Peter Ruane, Giovanni Di Perri, E Dejesus, Daniel Podzamczer, Gordon Crofoot
    Abstract:

    Summary Background Abacavir and tenofovir alafenamide offer reduced bone toxicity compared with tenofovir disoproxil fumarate. We aimed to compare safety and efficacy of tenofovir alafenamide plus Emtricitabine with that of abacavir plus lamivudine. Methods In this randomised, double-blind, active-controlled, non-inferiority phase 3 trial, HIV-1-positive adults (≥18 years) were screened at 79 sites in 11 countries in North America and Europe. Eligible participants were virologically suppressed (HIV-1 RNA vs other drug) at screening. Investigators, participants, and study staff giving treatment, assessing outcomes, and collecting data were masked to treatment group. The primary endpoint was the proportion of participants with virological suppression (HIV-1 RNA Findings Study enrolment began on June 29, 2015, and the cutoff enrolment date for the week 48 primary endpoint analysis was May 23, 2016. 501 participants were randomly assigned and treated. At week 48, virological suppression was maintained in 227 (90%) of 253 participants receiving tenofovir alafenamide plus Emtricitabine compared with 230 (93%) of 248 receiving abacavir plus lamivudine (difference −3·0%, 95% CI −8·2 to 2·0), showing non-inferiority. Few participants discontinued treatment because of adverse events: 12 (4%) of 280 participants in the tenofovir alafenimide plus Emtricitabine group and nine (3%) of 276 in the abacavir plus lamivudine group. Three participants had serious, treatment-related adverse events: one each with renal colic and neutropenia in the tenofovir alafenamide plus Emtricitabine group, and one myocardial infarction in the abacavir plus lamivudine group. There were no treatment-related deaths. Interpretation Tenofovir alafenamide, in combination with Emtricitabine and various third drugs, maintained high efficacy with a renal and bone safety profile similar to that of abacavir. In virologically suppressed patients, a regimen containing tenofovir alafenamide could be an alternative to those containing abacavir, without concern for new onset of renal or bone toxicities or hyperlipidaemia. Funding Gilead Sciences Inc.

  • switching from tenofovir disoproxil fumarate to tenofovir alafenamide coformulated with rilpivirine and Emtricitabine in virally suppressed adults with hiv 1 infection a randomised double blind multicentre phase 3b non inferiority study
    The Lancet HIV, 2017
    Co-Authors: Chloe Orkin, Gordon Crofoot, Peter Ruane, E Dejesus, Anthony Mills, Moti Ramgopal, Anthony Lamarca, Bernard Vandercam, Joseph De Wet, Jurgen K Rockstroh
    Abstract:

    Summary Background Tenofovir alafenamide, a tenofovir prodrug, results in 90% lower tenofovir plasma concentrations than does tenofovir disproxil fumarate, thereby minimising bone and renal risks. We investigated the efficacy, safety, and tolerability of switching to a single-tablet regimen containing rilpivirine, Emtricitabine, and tenofovir alafenamide compared with remaining on rilpivirine, Emtricitabine, and tenofovir disoproxil fumarate. Methods In this randomised, double-blind, multicentre, placebo-controlled, non-inferiority trial, HIV-1-infected adults were screened and enrolled at 119 hospitals in 11 countries in North America and Europe. Participants were virally suppressed (HIV-1 RNA Findings Between Jan 26, 2015, and Aug 25, 2015, 630 participants were randomised (316 to the tenofovir alafenamide group and 314 to the tenofovir disoproxil fumarate group). At week 48, 296 (94%) of 316 participants on tenofovir alafenamide and 294 (94%) of 313 on tenofovir disoproxil fumarate had maintained less than 50 copies per mL HIV-1 RNA (difference −0·3%, 95·001% CI −4·2 to 3·7), showing non-inferiority of tenofovir alafenamide to tenofovir disoproxil fumarate. Numbers of adverse events were similar between groups. 20 (6%) of 316 participants had study-drug related adverse events in the tenofovir alafenamide group compared with 37 (12%) of 314 in the tenofovir disoproxil fumarate group; none of these were serious. Interpretation Switching to rilpivirine, Emtricitabine, and tenofovir alafenamide was non-inferior to continuing rilpivirine, Emtricitabine, tenofovir disoproxil fumarate in maintaining viral suppression and was well tolerated at 48 weeks. These findings support guidelines recommending tenofovir alafenamide-based regimens, including coformulation with rilpivirine and Emtricitabine, as initial and ongoing treatment for HIV-1 infection. Funding Gilead Sciences.

  • switching from efavirenz Emtricitabine and tenofovir disoproxil fumarate to tenofovir alafenamide coformulated with rilpivirine and Emtricitabine in virally suppressed adults with hiv 1 infection a randomised double blind multicentre phase 3b non inf
    The Lancet HIV, 2017
    Co-Authors: E Dejesus, Hj Stellbrink, Gordon Crofoot, Peter Ruane, Carlos Martorell, Anthony Mills, Moti Ramgopal, Anthony Lamarca, Joseph De Wet, Jean Michel Molina
    Abstract:

    Summary Background Tenofovir alafenamide is a prodrug that reduces tenofovir plasma concentrations by 90% compared with tenofovir disoproxil fumarate, thereby decreasing bone and renal risks. The coformulation of rilpivirine, Emtricitabine, and tenofovir alafenamide has recently been approved, and we aimed to investigate the efficacy, safety, and tolerability of switching to this regimen compared with remaining on coformulated efavirenz, Emtricitabine, and tenofovir disoproxil fumarate. Methods In this randomised, double-blind, placebo-controlled, non-inferiority trial, HIV-1-infected adults were enrolled at 120 hospitals and outpatient clinics in eight countries in North America and Europe. Participants were virally suppressed (HIV-1 RNA Findings Between Jan 26, 2015, and Aug 27, 2015, 875 participants were randomly assigned and treated (438 with rilpivirine, Emtricitabine, and tenofovir alafenamide and 437 with efavirenz, Emtricitabine, tenofovir disoproxil fumarate). Viral suppression at week 48 was maintained in 394 (90%) of 438 participants assigned to the tenofovir alafenamide regimen and 402 (92%) of 437 assigned to the tenofovir disoproxil fumarate regimen (difference −2·0%, 95·001% CI −5·9 to 1·8), demonstrating non-inferiority. 56 (13%) of 438 in participants in the rilpivirine, Emtricitabine, and tenofovir alafenamide group experienced treatment-related adverse events compared with 45 (10%) of 437 in the efavirenz, Emtricitabine, and tenofovir disoproxil fumarate group. Interpretation Switching to rilpivirine, Emtricitabine, and tenofovir alafenamide from efavirenz, Emtricitabine, and tenofovir disoproxil fumarate was non-inferior in maintaining viral suppression and was well tolerated at 48 weeks. These findings support guidelines recommending tenofovir alafenamide-based regimens, including coformulation with rilpivirine and Emtricitabine, as initial and ongoing treatment for HIV-1 infection. Funding Gilead Sciences.

Jean Michel Molina - One of the best experts on this subject based on the ideXlab platform.

  • Emtricitabine and tenofovir alafenamide vs Emtricitabine and tenofovir disoproxil fumarate for hiv pre exposure prophylaxis discover primary results from a randomised double blind multicentre active controlled phase 3 non inferiority trial
    The Lancet, 2020
    Co-Authors: E Dejesus, Jean Michel Molina, Melanie A Thompson, Peter L. Anderson, Kenneth H Mayer, Karam Mounzer, Joss J De Wet, Heiko Jessen, Robert M Grant
    Abstract:

    Summary Background Tenofovir alafenamide shows high antiviral efficacy and improved renal and bone safety compared with tenofovir disoproxil fumarate when used for HIV treatment. Here, we report primary results from a blinded phase 3 study evaluating the efficacy and safety of pre-exposure prophylaxis (PrEP) with Emtricitabine and tenofovir alafenamide versus Emtricitabine and tenofovir disoproxil fumarate for HIV prevention. Methods This study is an ongoing, randomised, double-blind, multicentre, active-controlled, phase 3, non-inferiority trial done at 94 community, public health, and hospital-associated clinics located in regions of Europe and North America, where there is a high incidence of HIV or prevalence of people living with HIV, or both. We enrolled adult cisgender men who have sex with men and transgender women who have sex with men, both with a high risk of acquiring HIV on the basis of their self-reported sexual behaviour in the past 12 weeks or their recent history (within 24 weeks of enrolment) of bacterial sexually transmitted infections. Participants with current or previous use of PrEP with Emtricitabine and tenofovir disoproxil fumarate were not excluded. We used a computer-generated random allocation sequence to randomly assign (1:1) participants to receive either Emtricitabine (200 mg) and tenofovir alafenamide (25 mg) tablets daily, with matched placebo tablets (Emtricitabine and tenofovir alafenamide group), or Emtricitabine (200 mg) and tenofovir disoproxil fumarate (300 mg) tablets daily, with matched placebo tablets (Emtricitabine and tenofovir disoproxil fumarate group). As such, all participants were given two tablets. The trial sponsor, investigators, participants, and the study staff who provided the study drugs, assessed the outcomes, and collected the data were masked to group assignment. The primary efficacy outcome was incident HIV infection, which was assessed when all participants had completed 48 weeks of follow-up and half of all participants had completed 96 weeks of follow-up. This full analysis set included all randomly assigned participants who had received at least one dose of the assigned study drug and had at least one post-baseline HIV test. Non-inferiority of Emtricitabine and tenofovir alafenamide to Emtricitabine and tenofovir disoproxil fumarate was established if the upper bound of the 95·003% CI of the HIV incidence rate ratio (IRR) was less than the prespecified non-inferiority margin of 1·62. We prespecified six secondary bone mineral density and renal biomarker safety endpoints to evaluate using the safety analysis set. This analysis set included all randomly assigned participants who had received at least one dose of the assigned study drug. This trial is registered with ClinicalTrials.gov , NCT02842086 , and is no longer recruiting. Findings Between Sept 13, 2016, and June 30, 2017, 5387 (92%) of 5857 participants were randomly assigned and received Emtricitabine and tenofovir alafenamide (n=2694) or Emtricitabine and tenofovir disoproxil fumarate (n=2693). At the time of the primary efficacy analysis (ie, when all participants had completed 48 weeks and 50% had completed 96 weeks) Emtricitabine and tenofovir alafenamide was non-inferior to Emtricitabine and tenofovir disoproxil fumarate for HIV prevention, as the upper limit of the 95% CI of the IRR, was less than the prespecified non-inferiority margin of 1·62 (IRR 0·47 [95% CI 0·19–1·15]). After 8756 person-years of follow-up, 22 participants were diagnosed with HIV, seven participants in the Emtricitabine and tenofovir alafenamide group (0·16 infections per 100 person-years [95% CI 0·06–0·33]), and 15 participants in the Emtricitabine and tenofovir disoproxil fumarate group (0·34 infections per 100 person-years [0·19–0·56]). Both regimens were well tolerated, with a low number of participants reporting adverse events that led to discontinuation of the study drug (36 [1%] of 2694 participants in the Emtricitabine and tenofovir alafenamide group vs 49 [2%] of 2693 participants in the Emtricitabine and tenofovir disoproxil fumarate group). Emtricitabine and tenofovir alafenamide was superior to Emtricitabine and tenofovir disoproxil fumarate in all six prespecified bone mineral density and renal biomarker safety endpoints. Interpretation Daily Emtricitabine and tenofovir alafenamide shows non-inferior efficacy to daily Emtricitabine and tenofovir disoproxil fumarate for HIV prevention, and the number of adverse events for both regimens was low. Emtricitabine and tenofovir alafenamide had more favourable effects on bone mineral density and biomarkers of renal safety than Emtricitabine and tenofovir disoproxil fumarate. Funding Gilead Sciences.

  • bone mineral density in virologically suppressed people aged 60 years or older with hiv 1 switching from a regimen containing tenofovir disoproxil fumarate to an elvitegravir cobicistat Emtricitabine and tenofovir alafenamide single tablet regimen a
    The Lancet HIV, 2019
    Co-Authors: Franco Maggiolo, David Piontkowsky, Maria Gracia Mateogarcia, Yongwu Shao, Ian Mcnicholl, Federico Pulido, Francois Raffi, Giuliano Rizzardini, Jean Michel Molina, Richard Haubrich
    Abstract:

    Summary Background Tenofovir alafenamide is associated with less renal and bone toxicity than tenofovir disoproxil fumarate and might improve the long-term safety of antiretroviral therapy. We aimed to investigate the effect on bone mineral density of switching from a regimen containing tenofovir disoproxil fumarate to one containing tenofovir alafenamide in participants aged 60 years and older. Methods We did a prospective, open-label, multicentre, randomised trial in 36 European centres. Participants were virologically suppressed (HIV-1 RNA ClinicalTrials.gov , NCT02616783 . Findings Between Dec 22, 2015, and March 21, 2018, 167 participants were randomly assigned to elvitegravir, cobicistat, Emtricitabine, and tenofovir alafenamide (n=111 [66%]) or tenofovir disoproxil fumarate (n=56 [34%]). One participant in the elvitegravir, cobicistat, Emtricitabine, and tenofovir alafenamide group did not receive treatment and was excluded from all analyses. At week 48, the mean percentage change in spine bone mineral density was 2·24% (SD 3·27) in the elvitegravir, cobicistat, Emtricitabine, and tenofovir alafenamide group and −0·10% (3·39) in the tenofovir disoproxil fumarate group (between-group difference 2·43% [95% CI 1·34–3·52]; p Interpretation The significantly improved bone mineral density, overall safety, and efficacy data show the feasibility of switching from a regimen containing tenofovir disoproxil fumarate to elvitegravir, cobicistat, Emtricitabine, and tenofovir alafenamide in virologically suppressed people living with HIV aged 60 years or older. Funding Gilead Sciences.

  • a week 48 randomized phase 3 trial of darunavir cobicistat Emtricitabine tenofovir alafenamide in treatment naive hiv 1 patients
    AIDS, 2018
    Co-Authors: Joseph J. Eron, Erika Van Landuyt, Joel E Gallant, Jacques Reynes, Andrea Antinori, Chloe Orkin, Eugenia Negredo, Jean Michel Molina, Anthony Mills, Erkki Lathouwers
    Abstract:

    Objectives:To investigate efficacy and safety of a single-tablet regimen of darunavir/cobicistat/Emtricitabine/tenofovir alafenamide (D/C/F/TAF) 800/150/200/10 mg vs. darunavir/cobicistat plus Emtricitabine/tenofovir disoproxyl fumarate (TDF) (control) in antiretroviral-treatment-naive, HIV-1-infect

  • A week-48 randomized phase-3 trial of darunavir/cobicistat/Emtricitabine/tenofovir alafenamide in treatment-naive HIV-1 patients
    AIDS, 2018
    Co-Authors: Joseph J. Eron, Jacques Reynes, Andrea Antinori, Chloe Orkin, Eugenia Negredo, Jean Michel Molina, Anthony Mills, Joel Gallant, Erika Van Landuyt, Erkki Lathouwers
    Abstract:

    OBJECTIVES: To investigate efficacy and safety of a single-tablet regimen of darunavir/cobicistat/Emtricitabine/tenofovir alafenamide (D/C/F/TAF) 800/150/200/10 mg vs. darunavir/cobicistat plus Emtricitabine/tenofovir disoproxyl fumarate (TDF) (control) in antiretroviral-treatment-naive, HIV-1-infected adults. DESIGN: Phase-3, randomized, active-controlled, double-blind, international, multicenter, noninferiority study (NCT02431247). METHODS: Seven hundred and twenty-five participants were randomized (1 : 1) to D/C/F/TAF (362) or control (363). The primary objective was to demonstrate noninferiority of D/C/F/TAF vs. control for percentage viral load less than 50 copies/ml (FDA-snapshot analysis) at 48 weeks (10% margin). RESULTS: At week 48, D/C/F/TAF was noninferior to control (91.4 vs. 88.4% achieved viral load

  • switching to fixed dose bictegravir Emtricitabine and tenofovir alafenamide from dolutegravir plus abacavir and lamivudine in virologically suppressed adults with hiv 1 48 week results of a randomised double blind multicentre active controlled phase
    The Lancet HIV, 2018
    Co-Authors: Jean Michel Molina, Luis F Lopezcortes, Peter Ruane, Daniel Podzamczer, Cynthia Brinson, Anthony Mills, Douglas J. Ward, Indira Brar, Joseph Custodio
    Abstract:

    Summary Background Bictegravir, co-formulated with Emtricitabine and tenofovir alafenamide, has shown good efficacy and tolerability, and similar bone, renal, and lipid profiles to dolutegravir, abacavir, and lamivudine, in treatment-naive adults with HIV-1 infection, without development of treatment-emergent resistance. Here, we report 48-week results of a phase 3 study investigating switching to bictegravir, Emtricitabine, and tenofovir alafenamide from dolutegravir, abacavir, and lamivudine in virologically suppressed adults with HIV-1 infection. Methods In this multicentre, randomised, double-blind, active-controlled, non-inferiority, phase 3 trial, HIV-1-infected adults were enrolled at 96 outpatient centres in nine countries. Eligible participants were aged 18 years or older and on a regimen of 50 mg dolutegravir, 600 mg abacavir, and 300 mg lamivudine (fixed-dose combination or multi-tablet regimen); had an estimated glomerular filtration rate of 50 mL/min or higher; and had been virologically suppressed (plasma HIV-1 RNA Findings Between Nov 11, 2015, and July 6, 2016, 567 participants were randomly assigned and 563 were treated (282 received bictegravir, Emtricitabine, and tenofovir alafenamide, and 281 received dolutegravir, abacavir, and lamivudine). Switching to the bictegravir regimen was non-inferior to remaining on dolutegravir, abacavir, and lamivudine for the primary outcome: three (1%) of 282 in the bictegravir group had HIV-1 RNA of 50 copies per mL or higher at week 48 versus one ( Interpretation The fixed-dose combination of bictegravir, Emtricitabine, and tenofovir alafenamide might provide a safe and efficacious option for ongoing treatment of HIV-1 infection. Funding Gilead Sciences.

Chloe Orkin - One of the best experts on this subject based on the ideXlab platform.

  • fixed dose combination bictegravir Emtricitabine and tenofovir alafenamide versus dolutegravir containing regimens for initial treatment of hiv 1 infection week 144 results from two randomised double blind multicentre phase 3 non inferiority trials
    The Lancet HIV, 2020
    Co-Authors: Chloe Orkin, Hj Stellbrink, Franco Maggiolo, E Dejesus, Carlos Martorell, David A Wohl, Jeffrey L Stephens, Samir K. Gupta, Jose R. Arribas, Melanie A Thompson
    Abstract:

    Summary Background In the primary week-48 analyses of two phase 3 studies, coformulated bictegravir, Emtricitabine, and tenofovir alafenamide was non-inferior to a dolutegravir-containing regimen in treatment-naive people with HIV. We report week-144 efficacy and safety results from these studies. Methods We did two double-blind, active-controlled studies (now in open-label extension phase). Study 1 randomly assigned (1:1) HLA-B*5701-negative adults without hepatitis B virus co-infection to receive coformulated bictegravir 50 mg, Emtricitabine 200 mg, and tenofovir alafenamide 25 mg, or coformulated dolutegravir 50 mg, abacavir 600 mg, and lamivudine 300 mg once daily. Study 2 randomly assigned (1:1) adults to bictegravir, Emtricitabine, and tenofovir alafenamide, or dolutegravir 50 mg given with coformulated Emtricitabine 200 mg and tenofovir alafenamide 25 mg. We previously reported non-inferiority at the primary endpoint. Here, we report the week-144 secondary outcome of proportion of participants with plasma HIV-1 RNA less than 50 copies per mL at week 144, by US Food and Drug Administration Snapshot algorithm, analysed in the same manner. These studies were registered with ClinicalTrials.gov , NCT02607930 and NCT02607956 . Findings 629 participants were randomly assigned and treated in study 1 (314 to bictegravir, Emtricitabine, and tenofovir alafenamide, and 315 to dolutegravir, abacavir, and lamivudine) and 645 in study 2 (327 to bictegravir, Emtricitabine, and tenofovir alafenamide, 325 to dolutegravir, Emtricitabine, tenofovir alafenamide). At week 144, bictegravir, Emtricitabine, and tenofovir alafenamide was non-inferior to both dolutegravir-containing regimens for efficacy. In study 1, 256 (82%) of 314 participants had plasma HIV-1 RNA less than 50 copies per mL in the bictegravir, Emtricitabine, and tenofovir alafenamide group and 265 (84%) of 315 in the dolutegravir, abacavir, and lamivudine group (difference −2·6%, 95% CI −8·5 to 3·4). In study 2, 262 (82%) of 320 participants had plasma HIV-1 RNA less than 50 copies per mL in the bictegravir, Emtricitabine, and tenofovir alafenamide group and 273 (84%) of 325 in the dolutegravir, Emtricitabine, and tenofovir alafenamide group (difference −1·9%, −7·8 to 3·9). In both studies, no participant had treatment-emergent resistance to study drugs up to week 144. All treatment regimens were well tolerated with additional exposure. Adverse events that led to study drug discontinuation were reported for no participants in the bictegravir, Emtricitabine, and tenofovir alafenamide group versus five (2%) of 315 in the dolutegravir, abacavir, and lamivudine group (study 1), and six (2%) of 320 in the bictegravir, Emtricitabine, and tenofovir alafenamide versus six (2%) of 325 in the dolutegravir, Emtricitabine, and tenofovir alafenamide group (study 2). In study 1, statistically significant differences were observed in median changes from baseline in fasting total cholesterol (14 mg/dL vs 10 mg/dL; p=0·034), direct LDL (21 mg/dL vs 14 mg/dL; p=0·004), and total cholesterol to HDL ratio (−0·1 vs −0·3; p=0·007) at week 144; no differences were observed between groups in study 2. Weight gain was seen across all treatment groups in both studies, with no differences in median changes from baseline in weight at week 144 for either study. Interpretation These long-term data support the use of bictegravir, Emtricitabine, and tenofovir alafenamide as a safe, well tolerated, and durable treatment for people with HIV, with no emergent resistance. Funding Gilead Sciences.

  • Week 96 efficacy and safety results of the phase 3, randomized EMERALD trial to evaluate switching from boosted-protease inhibitors plus Emtricitabine/tenofovir disoproxil fumarate regimens to the once daily, single-tablet regimen of darunavir/cobicistat/Emtricitabine/tenofovir alafenamide (D/C/F/TAF) in treatment-experienced, virologically-suppressed adults living with HIV-1
    Antiviral Research, 2019
    Co-Authors: Joseph J. Eron, Erkki Lathouwers, Federico Pulido, Chloe Orkin, Douglas Cunningham, Frank Post, Stéphane De Wit, Veerle Hufkens, John Jezorwski, Romana Petrovic
    Abstract:

    Darunavir/cobicistat/Emtricitabine/tenofovir alafenamide (D/C/F/TAF) 800/150/200/10 mg was investigated through 96 weeks in EMERALD (NCT02269917). Virologically-suppressed, HIV-1-positive treatment-experienced adults (previous non-darunavir virologic failure [VF] allowed) were randomized (2:1) to D/C/F/TAF or boosted protease inhibitor (PI) plus Emtricitabine/tenofovir-disoproxil-fumarate (F/TDF) over 48 weeks. At week 52 participants in the boosted PI arm were offered switch to D/C/F/TAF (late-switch, 44 weeks D/C/F/TAF exposure). All participants were followed on D/C/F/TAF until week 96. Efficacy endpoints were percentage cumulative protocol-defined virologic rebound (PDVR; confirmed viral load [VL] ≥50 copies/mL) and VL 

  • a week 48 randomized phase 3 trial of darunavir cobicistat Emtricitabine tenofovir alafenamide in treatment naive hiv 1 patients
    AIDS, 2018
    Co-Authors: Joseph J. Eron, Erika Van Landuyt, Joel E Gallant, Jacques Reynes, Andrea Antinori, Chloe Orkin, Eugenia Negredo, Jean Michel Molina, Anthony Mills, Erkki Lathouwers
    Abstract:

    Objectives:To investigate efficacy and safety of a single-tablet regimen of darunavir/cobicistat/Emtricitabine/tenofovir alafenamide (D/C/F/TAF) 800/150/200/10 mg vs. darunavir/cobicistat plus Emtricitabine/tenofovir disoproxyl fumarate (TDF) (control) in antiretroviral-treatment-naive, HIV-1-infect

  • A week-48 randomized phase-3 trial of darunavir/cobicistat/Emtricitabine/tenofovir alafenamide in treatment-naive HIV-1 patients
    AIDS, 2018
    Co-Authors: Joseph J. Eron, Jacques Reynes, Andrea Antinori, Chloe Orkin, Eugenia Negredo, Jean Michel Molina, Anthony Mills, Joel Gallant, Erika Van Landuyt, Erkki Lathouwers
    Abstract:

    OBJECTIVES: To investigate efficacy and safety of a single-tablet regimen of darunavir/cobicistat/Emtricitabine/tenofovir alafenamide (D/C/F/TAF) 800/150/200/10 mg vs. darunavir/cobicistat plus Emtricitabine/tenofovir disoproxyl fumarate (TDF) (control) in antiretroviral-treatment-naive, HIV-1-infected adults. DESIGN: Phase-3, randomized, active-controlled, double-blind, international, multicenter, noninferiority study (NCT02431247). METHODS: Seven hundred and twenty-five participants were randomized (1 : 1) to D/C/F/TAF (362) or control (363). The primary objective was to demonstrate noninferiority of D/C/F/TAF vs. control for percentage viral load less than 50 copies/ml (FDA-snapshot analysis) at 48 weeks (10% margin). RESULTS: At week 48, D/C/F/TAF was noninferior to control (91.4 vs. 88.4% achieved viral load

  • bictegravir Emtricitabine and tenofovir alafenamide versus dolutegravir abacavir and lamivudine for initial treatment of hiv 1 infection gs us 380 1489 a double blind multicentre phase 3 randomised controlled non inferiority trial
    The Lancet, 2017
    Co-Authors: Joel E Gallant, Pablo Tebas, Chloe Orkin, Daniel Podzamczer, Anthony Mills, Adriano Lazzarin, Eric S. Daar, Pierre Marie Girard, Indira Brar, David A Wohl
    Abstract:

    Summary Background Integrase strand transfer inhibitors (INSTIs) are recommended components of initial antiretroviral therapy with two nucleoside reverse transcriptase inhibitors. Bictegravir is a novel, potent INSTI with a high in-vitro barrier to resistance and low potential as a perpetrator or victim of clinically relevant drug–drug interactions. We aimed to assess the efficacy and safety of bictegravir coformulated with Emtricitabine and tenofovir alafenamide as a fixed-dose combination versus coformulated dolutegravir, abacavir, and lamivudine. Methods We did this double-blind, multicentre, active-controlled, randomised controlled non-inferiority trial at 122 outpatient centres in nine countries in Europe, Latin America, and North America. We enrolled HIV-1 infected adults (aged ≥18 years) who were previously untreated (HIV-1 RNA ≥500 copies per mL); HLA-B*5701 -negative; had no hepatitis B virus infection; screening genotypes showing sensitivity to Emtricitabine, tenofovir, lamivudine, and abacavir; and an estimated glomerular filtration rate of 50 mL/min or more. Participants were randomly assigned (1:1), via a computer-generated allocation sequence (block size of four), to receive coformulated bictegravir 50 mg, Emtricitabine 200 mg, and tenofovir alafenamide 25 mg or coformulated dolutegravir 50 mg, abacavir 600 mg, and lamivudine 300 mg, with matching placebo, once daily for 144 weeks. Randomisation was stratified by HIV-1 RNA (≤100 000 copies per mL, >100 000 to ≤400 000 copies per mL, or >400 000 copies per mL), CD4 count ( Findings Between Nov 13, 2015, and July 14, 2016, we randomly assigned 631 participants to receive coformulated bictegravir, Emtricitabine, and tenofovir alafenamide (n=316) or coformulated dolutegravir, abacavir, and lamivudine (n=315), of whom 314 and 315 patients, respectively, received at least one dose of study drug. At week 48, HIV-1 RNA less than 50 copies per mL was achieved in 92·4% of patients (n=290 of 314) in the bictegravir, Emtricitabine, and tenofovir alafenamide group and 93·0% of patients (n=293 of 315) in the dolutegravir, abacavir, and lamivudine group (difference −0·6%, 95·002% CI −4·8 to 3·6; p=0·78), demonstrating non-inferiority of bictegravir, Emtricitabine, and tenofovir alafenamide to dolutegravir, abacavir, and lamivudine. No individual developed treatment-emergent resistance to any study drug. Incidence and severity of adverse events was mostly similar between groups except for nausea, which occurred less frequently in patients given bictegravir, Emtricitabine, and tenofovir alafenamide than in those given dolutegravir, abacavir, and lamivudine (10% [n=32] vs 23% [n=72]; p vs 40% [n=127]), the difference being driven by a higher incidence of drug-related nausea in the dolutegravir, abacavir, and lamivudine group (5% [n=17] vs 17% [n=55]; p Interpretation At 48 weeks, coformulated bictegravir, Emtricitabine, and tenofovir alafenamide achieved virological suppression in 92% of previously untreated adults and was non-inferior to coformulated dolutegravir, abacavir, and lamivudine, with no treatment-emergent resistance. Bictegravir, Emtricitabine, and tenofovir alafenamide was safe and well tolerated with better gastrointestinal tolerability than dolutegravir, abacavir, and lamivudine. Because coformulated bictegravir, Emtricitabine, and tenofovir alafenamide does not require HLA B*5701 testing and provides guideline-recommended treatment for individuals co-infected with HIV and hepatitis B, this regimen might lend itself to rapid or same-day initiation of therapy in the clinical setting. Funding Gilead Sciences.

David Piontkowsky - One of the best experts on this subject based on the ideXlab platform.

  • bone mineral density in virologically suppressed people aged 60 years or older with hiv 1 switching from a regimen containing tenofovir disoproxil fumarate to an elvitegravir cobicistat Emtricitabine and tenofovir alafenamide single tablet regimen a
    The Lancet HIV, 2019
    Co-Authors: Franco Maggiolo, David Piontkowsky, Maria Gracia Mateogarcia, Yongwu Shao, Ian Mcnicholl, Federico Pulido, Francois Raffi, Giuliano Rizzardini, Jean Michel Molina, Richard Haubrich
    Abstract:

    Summary Background Tenofovir alafenamide is associated with less renal and bone toxicity than tenofovir disoproxil fumarate and might improve the long-term safety of antiretroviral therapy. We aimed to investigate the effect on bone mineral density of switching from a regimen containing tenofovir disoproxil fumarate to one containing tenofovir alafenamide in participants aged 60 years and older. Methods We did a prospective, open-label, multicentre, randomised trial in 36 European centres. Participants were virologically suppressed (HIV-1 RNA ClinicalTrials.gov , NCT02616783 . Findings Between Dec 22, 2015, and March 21, 2018, 167 participants were randomly assigned to elvitegravir, cobicistat, Emtricitabine, and tenofovir alafenamide (n=111 [66%]) or tenofovir disoproxil fumarate (n=56 [34%]). One participant in the elvitegravir, cobicistat, Emtricitabine, and tenofovir alafenamide group did not receive treatment and was excluded from all analyses. At week 48, the mean percentage change in spine bone mineral density was 2·24% (SD 3·27) in the elvitegravir, cobicistat, Emtricitabine, and tenofovir alafenamide group and −0·10% (3·39) in the tenofovir disoproxil fumarate group (between-group difference 2·43% [95% CI 1·34–3·52]; p Interpretation The significantly improved bone mineral density, overall safety, and efficacy data show the feasibility of switching from a regimen containing tenofovir disoproxil fumarate to elvitegravir, cobicistat, Emtricitabine, and tenofovir alafenamide in virologically suppressed people living with HIV aged 60 years or older. Funding Gilead Sciences.

  • correction an indirect comparison of efficacy and safety of elvitegravir cobicistat Emtricitabine tenofovir disoproxil fumarate and abacavir lamivudine dolutegravir in initial therapy
    PLOS ONE, 2016
    Co-Authors: Josep M Llibre, David Piontkowsky, Georg M N Behrens, Stephane Bouee, Geraldine Reilly, Peter Borg, Francois Raffi, Graeme Moyle, Felipe Rogatto
    Abstract:

    Objectives The objective of this analysis is to perform an indirect comparison of elvitegravir, cobicistat, Emtricitabine and tenofovir DF (E/C/F/TDF) to abacavir/lamivudine and dolutegravir (ABC/3TC + DTG) by using 2 trials evaluating each of these regimens in comparison to efavirenz, Emtricitabine and tenofovir DF (EFV/FTC/TDF).

  • switching to coformulated elvitegravir cobicistat Emtricitabine and tenofovir versus continuation of non nucleoside reverse transcriptase inhibitor with Emtricitabine and tenofovir in virologically suppressed adults with hiv strategy nnrti 48 week results of a randomised open label phase 3b non inferiority trial
    Lancet Infectious Diseases, 2014
    Co-Authors: Anton Pozniak, Hj Stellbrink, Anthony Mills, Thai Nguyen, Keith Henry, Pere Domingo, Martin Markowitz, Antonio Antela, P M Girard, David Piontkowsky
    Abstract:

    Summary Background Coformulated elvitegravir, cobicistat, Emtricitabine, and tenofovir disoproxil fumarate (tenofovir) might be a safe and efficacious switch option for virologically suppressed patients with HIV who have neuropsychiatric side-effects on a non-nucleoside reverse transcriptase inhibitor (NNRTI) or who are on a multitablet NNRTI-containing regimen and want a regimen simplification. We assessed the non-inferiority of such a switch compared with continuation of an NNRTI-containing regimen. Methods STRATEGY-NNRTI is a 96 week, international, multicentre, randomised, open-label, phase 3b, non-inferiority trial enrolling adults (≥18 years) with HIV-1 and plasma HIV RNA viral load below 50 copies per mL for at least 6 months on an NNRTI plus Emtricitabine and tenofovir regimen. With a computer-generated randomisation sequence, we randomly allocated participants (2:1; blocks of six, stratified by efavirenz use at screening) to switch to coformulated elvitegravir, cobicistat, Emtricitabine, and tenofovir (switch group) or continue the NNRTI plus Emtricitabine and tenofovir regimen (no-switch group). Key eligibility criteria included no history of virological failure and an estimated glomerular filtration rate of 70 mL per min or greater. The primary endpoint was the proportion of participants with plasma viral loads below 50 copies per mL at week 48 based on a snapshot algorithm with a non-inferiority margin of 12% (assessed by modified intention to treat). This trial is ongoing and is registered at ClinicalTrials.gov, number NCT01495702. Findings Between Dec 29, 2011, and Dec 13, 2012, we randomly allocated 439 participants to treatment: 290 participants in the switch group and 143 participants in the no-switch group received treatment and were included in the modified intention-to-treat population. At week 48, 271 (93%) of 290 participants in the switch group and 126 (88%) of 143 participants in the no-switch group maintained plasma viral loads below 50 copies per mL (difference 5·3%, 95% CI −0·5 to 12·0; p=0·066). We detected no treatment-emergent resistance in either group. Safety events leading to discontinuation were uncommon in both groups: six (2%) of 291 participants in the switch group and one (1%) of 143 in the no-switch group. Interpretation Coformulated elvitegravir, cobicistat, Emtricitabine, and tenofovir seems to be efficacious and well tolerated in virologically suppressed adults with HIV and might be a suitable alternative for patients on an NNRTI with Emtricitabine and tenofovir regimen considering a regimen modification or simplification. Funding Gilead Sciences.

  • simplification to coformulated elvitegravir cobicistat Emtricitabine and tenofovir versus continuation of ritonavir boosted protease inhibitor with Emtricitabine and tenofovir in adults with virologically suppressed hiv strategy pi 48 week results of a randomised open label phase 3b non inferiority trial
    Lancet Infectious Diseases, 2014
    Co-Authors: Jose R. Arribas, Jacques Reynes, Pablo Tebas, Giovanni Di Perri, Thai Nguyen, Kirsten L. White, Gilles Pialoux, Joseph Gathe, Ramin Ebrahimi, David Piontkowsky
    Abstract:

    Summary Background Patients with HIV on antiretroviral therapy might benefit from regimen simplification to reduce pill burden and dosing frequency. We aimed to assess the safety and efficacy of simplifying the treatment regimen for adults with virologically suppressed HIV infection from a ritonavir-boosted protease inhibitor and Emtricitabine plus tenofovir disoproxil fumarate (tenofovir) regimen to coformulated elvitegravir, cobicistat, Emtricitabine, and tenofovir. Methods STRATEGY-PI is a 96 week, international, multicentre, randomised, open-label, phase 3b trial in which HIV-infected adults with a plasma HIV-1 RNA viral load of less than 50 copies per mL for at least 6 months who were taking a ritonavir-boosted protease inhibitor with Emtricitabine plus tenofovir were randomly assigned (2:1) either to switch to coformulated elvitegravir, cobicistat, Emtricitabine, and tenofovir or to continue on their existing regimen. Key eligibility criteria included no history of virological failure, no resistance to Emtricitabine and tenofovir, and creatinine clearance of 70 mL/min or higher. Neither participants nor investigators were masked to group allocation. The primary endpoint was the proportion of participants with a viral load of less than 50 copies per mL at week 48, based on a US Food and Drug Administration snapshot algorithm for the modified intention-to-treat population, which excluded major protocol violations (prohibited resistance or not receiving a protease inhibitor at baseline). We prespecified non-inferiority with a 12% margin; if non-inferiority was established, superiority was tested as per a prespecified sequential testing procedure. This trial is registered at ClinicalTrials.gov, number NCT01475838. Findings Between Dec 12, 2011, and Dec 20, 2012, 433 participants were randomly assigned and received at least one dose of study drug. Of these participants, 293 were assigned to switch to the simplified regimen (switch group) and 140 to remain on their existing regimen (no-switch group); after exclusions, 290 and 139 participants, respectively, were analysed in the modified intention-to-treat population. At week 48, 272 (93·8%) of 290 participants in the switch group maintained a viral load of less than 50 copies per mL, compared with 121 (87·1%) of 139 in the no-switch group (difference 6·7%, 95% CI 0·4–13·7; p=0·025). The statistical superiority of the simplified regimen was mainly caused by a higher proportion of participants in the no-switch group than in the switch group discontinuing treatment for non-virological reasons; virological failure was rare in both groups (two [1%] of 290 vs two [1%] of 139). We did not detect any treatment-emergent resistance in either group. Adverse events leading to discontinuation were rare in both groups (six [2%] of 293 vs four [3%] of 140). Switching to the simplified regimen was associated with a small, non-progressive increase from baseline in serum creatinine concentration. Nausea was more common in the switch group than in the no-switch group, but rates of diarrhoea and bloating decreased compared with baseline from week 4 to week 48 in the switch group, whereas there were generally no changes for these symptoms in the no-switch group. Interpretation Coformulated elvitegravir, cobicistat, Emtricitabine, and tenofovir might be a useful regimen simplification option for virologically supressed adults with HIV taking a multitablet ritonavir-boosted protease inhibitor regimen. Funding Gilead Sciences.