Raltegravir 1200 mg Once Daily vs 400 mg Twice Daily, With Emtricitabine and Tenofovir Disoproxil Fumarate, for Previously Untreated HIV-1 Infection: Week 96 Results From ONCEMRK, a Randomized, Double-Blind, Noninferiority Trial

Cahn, Pedro; Sax, Paul E.; Squires, Kathleen; Molina, Jean‐Michel; Ratanasuwan, Winai; Rassool, Mohammed; Bloch, Mark; Xu, Xia; Zhou, Yan; Homony, Brenda; Hepler, Deborah A.; Teppler, Hedy; Hanna, George J.; Nguyen, Bach‐Yen; Greaves, Wayne

doi:10.1097/qai.0000000000001723

Cited by 23 publications

(15 citation statements)

References 29 publications

(20 reference statements)

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“…11 Among ART-naïve PLWH in the ONCEMRK trial, the cumulative incidence of moderate LCE with RAL use ranged from 1.5% to 4.5%, depending on the specific liver enzyme; the cumulative incidence of severe LCE ranged from 0.4% to 2.1% and there were zero grade 4 elevations of AST. 10 Among ART-experienced PLWH taking RAL in the BENCHMRK trials, the cumulative incidence of severe LCE ranged from 1% to 4% at 96 weeks, 1% to 5% at 156 weeks, and 2% to 5% at 240 weeks; there was no difference between the RAL and placebo groups. 12 Trials of DRV among ART-naïve PLWH (ARTEMIS trial) 8,25 and ART-experienced PLWH (TITAN study) 13 report combined moderate and severe LCE proportions that ranged from 1% to 9% at 48 weeks and 1% to 13% at 192 weeks.…”

Section: Discussionmentioning

confidence: 95%

“…8 With raltegravir (RAL) initiation, incidence of grade 3-4 LCE was 5% over 48 weeks; incidence of LCE was up to 2% (grade 3) and up to 1% (grade 4) over 96 weeks. 9,10 Similarly, LCE has been reported as a rare occurrence in clinical trials of treatment-experienced PLWH. With a switch to EVG, the incidence of grade 3-4 LCE was 2% over 48 weeks.…”

Section: Introductionmentioning

confidence: 99%

“…8 With raltegravir (RAL) initiation, incidence of grade 3–4 LCE was 5% over 48 weeks; incidence of LCE was up to 2% (grade 3) and up to 1% (grade 4) over 96 weeks. 9,10…”

Section: Introductionmentioning

confidence: 99%

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Antiretroviral therapy and liver disorders in the OPERA^® cohort

Wohlfeiler

Mounzer

Brunet³

et al. 2020

Therapeutic Advances in Drug Safety

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Introduction: A comprehensive assessment of liver disorders was conducted among people living with HIV (PLWH) on a new antiretroviral regimen based on common core agents. Methods: Treatment-naïve and experienced PLWH first initiating dolutegravir (DTG), elvitegravir (EVG), raltegravir (RAL), or darunavir (DRV) in the OPERA® cohort were included if they had ⩾1 liver chemistry test performed both within 12 months before regimen start and over follow-up. Liver disorders were defined as a diagnosis of drug-induced liver injury (DILI) or moderate/severe liver chemistry elevations (LCE). History of liver disorders experienced within 12 months of initiation was summarized. Liver disorders occurring during follow-up were described as prevalent (all disorders) or incident (disorders occurring among PLWH without a history of liver disorders or advanced liver fibrosis). Results: Out of 16,024 PLWH, 38% initiated DTG, 43% EVG, 5% RAL, and 14% DRV. EVG users were younger and had a lower likelihood of comorbidities or lipid-lowering agent use than DTG users. EVG users were significantly less likely to have a history of moderate/severe LCE or to have prevalent moderate LCE. RAL users were older and had a higher likelihood of comorbidities or lipid-lowering agent use than DTG users. RAL users were significantly more likely to have a history of advanced liver fibrosis and prevalent moderate/severe LCE during follow-up. DRV users were older and had a lower likelihood of lipid-lowering agent use than DTG users. There was no difference in history of LCE, nor in prevalent or incident LCE between DRV and DTG users. No DILI diagnoses were recorded. Discontinuation following a liver disorder was rare (<1%) across all groups. Conclusion: While PLWH with comorbidities may have been channeled away from EVG and toward DTG and RAL, the incidence of moderate/severe LCE did not differ between DTG and EVG, RAL, and DRV. Plain language summary Liver disorders and HIV treatment A comprehensive assessment of liver disorders was conducted using data from the OPERA® cohort, which provides anonymous patient-level clinical data from electronic health records. People living with HIV (PLWH) who were starting a new HIV treatment regimen that included one of four common HIV drugs were included in this study. Liver disorders included drug-induced liver injury (DILI) and moderate or severe liver chemistry elevations. History of a disorder was defined as liver disorders that occurred before starting the new treatment. Prevalent disorders were those that occurred after starting the new treatment in the whole population. Incident disorders were those that occurred after starting the new treatment, but only among PLWH without any history of liver disorders. Out of 16,024 PLWH, 38% initiated dolutegravir (DTG), 43% elvitegravir (EVG), 5% raltegravir (RAL), and 14% darunavir (DRV). EVG users were younger and less likely to have other diseases or use cholesterol lowering drugs compared to DTG users. They were also less likely to have a history of moderate/severe liver chemistry elevations or to have prevalent moderate liver chemistry elevations. RAL users were older and more likely to have other diseases or use cholesterol lowering drugs compared to DTG users. They were also more likely to have prevalent moderate/severe liver chemistry elevations than DTG users. DRV users were older and less likely to use cholesterol lowering agents compared to DTG users. There was no difference in history of liver chemistry elevations, or in prevalent, or incident liver chemistry elevations between DRV and DTG users. There were no DILI diagnoses and discontinuation of treatment following liver disorders was rare across all groups. Overall, the incidence of liver disorders after starting a new HIV treatment regimen did not differ between four common antiretroviral drugs.

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Section: Discussionmentioning

confidence: 95%

Section: Introductionmentioning

confidence: 99%

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Antiretroviral therapy and liver disorders in the OPERA^® cohort

Wohlfeiler

Mounzer

Brunet³

et al. 2020

Therapeutic Advances in Drug Safety

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“…regimen demonstrated non‐inferior efficacy and similar safety to the 400 mg b.i.d. regimen at 96 weeks 6,7 . The 600 mg formulation can be dosed once‐daily because of the less erratic absorption, higher bioavailability, higher loading dose and decreased influence of concomitant food intake 8 .…”

Section: Introductionmentioning

confidence: 99%

A population pharmacokinetics analysis assessing the exposure of raltegravir once‐daily 1200 mg in pregnant women living with HIV

Bukkems¹,

Post²,

Burger³

et al. 2021

CPT Pharmacom & Syst Pharma

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“…Es importante anotar que la resistencia a los ARV en el momento del fracaso virológico fue rara, pero más frecuente en el brazo de RAL (3%) que en el de inhibidores de PR (1.5%)59 .En un ensayo clínico aleatorizado, doble ciego, RAL 1200 mg una vez al día más TDF/FTC versus RAL 400 mg dos veces al día más TDF/FTC a las 96 semanas lograron la supresión del ARN del VIH (81.5% en el grupo de una vez al día frente a 80.1% en el grupo de dos veces al día), las respuestas fueron similares independientemente del nivel inicial de ARN del VIH o el recuento de T CD4+. La presentación de RAL de 600mg en el momento de esta revisión, no está disponible para Colombia60 .En pacientes experimentados, los estudios BENCHMRK 161 y BENCHMRK 230 , los cuales son ensayos clínicos en fase III, paralelos, aleatorizados, doble ciegos y controlados con placebo, analizaron la eficacia y seguridad de RAL en el rescate de pacientes infectados por los VIH expuestos a múltiples fármacos ARV y en situación de fracaso virológico. Los criterios de inclusión fueron: carga viral > 1000 copias/ml y presencia de resistencia genotípica o fenotípica al menos a un fármaco de cada una de las 3 clases de ARV más utilizadas: ITRN, ITRNN e IP.…”

unclassified

Inhibidores de Transferencia de la Cadena de Integrasa: Bases para su uso en la práctica clínica

Gualtero

Valderrama

Quiroga

et al. 2018

Infect

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Los inhibidores de transferencia de la cadena de integrasa (INSTI) son medicamentos cuyo mecanismo de acción consiste en bloquear el proceso de integración del ADN proviral al ADN del hospedero mediante la unión al sitio catalítico de la integrasa viral y de esta manera evitar su replicación. Actualmente se cuenta con la aprobación INSTI de primera y segunda generación, presentan similitud en su mecanismo de acción, cambios en su estructura que modifican su barrera genética, pero mantienen su perfil de seguridad y efectividad. Desde su aprobación en el año 2007, se han llevado a cabo múltiples estudios clínicos cuyos resultados han permitido avanzar en el conocimiento de su efectividad en diferentes escenarios clínicos; (pacientes naive, experimentados, esquemas de simplificación y profilaxis, así, como en el conocimiento de su perfil de mutaciones de resistencia). En el presente artículo se hizo una revisión de los miembros de esta familia de antirretrovirales (ARV).

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Raltegravir 1200 mg Once Daily vs 400 mg Twice Daily, With Emtricitabine and Tenofovir Disoproxil Fumarate, for Previously Untreated HIV-1 Infection: Week 96 Results From ONCEMRK, a Randomized, Double-Blind, Noninferiority Trial

Abstract: Supplemental Digital Content is Available in the Text.

Cited by 23 publications

References 29 publications

Antiretroviral therapy and liver disorders in the OPERA^® cohort

Antiretroviral therapy and liver disorders in the OPERA^® cohort

A population pharmacokinetics analysis assessing the exposure of raltegravir once‐daily 1200 mg in pregnant women living with HIV

Inhibidores de Transferencia de la Cadena de Integrasa: Bases para su uso en la práctica clínica

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Raltegravir 1200 mg Once Daily vs 400 mg Twice Daily, With Emtricitabine and Tenofovir Disoproxil Fumarate, for Previously Untreated HIV-1 Infection: Week 96 Results From ONCEMRK, a Randomized, Double-Blind, Noninferiority Trial

Abstract: Supplemental Digital Content is Available in the Text.

Cited by 23 publications

References 29 publications

Antiretroviral therapy and liver disorders in the OPERA® cohort

Antiretroviral therapy and liver disorders in the OPERA® cohort

A population pharmacokinetics analysis assessing the exposure of raltegravir once‐daily 1200 mg in pregnant women living with HIV

Inhibidores de Transferencia de la Cadena de Integrasa: Bases para su uso en la práctica clínica

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Product

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Antiretroviral therapy and liver disorders in the OPERA^® cohort

Antiretroviral therapy and liver disorders in the OPERA^® cohort