Efficacy and safety of dolutegravir–rilpivirine for maintenance of virological suppression in adults with HIV-1: 100-week data from the randomised, open-label, phase 3 SWORD-1 and SWORD-2 studies

Aboud, Michael; Orkin, Chloe; Podzamczer, Daniel; Bogner, Johannes R.; Baker, David; Khuong-Josses, Marie-Aude; Parks, David; Angelis, Konstantinos; Kahl, Lesley; Blair, Elizabeth A.; Adkison, Kimberly K.; Underwood, Mark; Matthews, James L.; Wynne, Brian; Vandermeulen, Kati; Gartland, Martin; Smith, Kimberly Y.

doi:10.1016/s2352-3018(19)30149-3

Cited by 99 publications

(109 citation statements)

References 18 publications

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“…In OPERA, there was no association between regimen type and time to virologic suppression among patients who were viraemic at regimen initiation. Previous trials have not evaluated suppression among viraemic patients, but have assessed the difference in maintenance of suppression between 2‐DR and 3‐DR groups . In the SWORD‐1 and SWORD‐2 trials, the 48 weeks adjusted difference in suppression maintenance between the 2‐DR (DTG + RPV) and the 3‐DR arms was −0.2% (95% CI: −3.0, 2.5) .…”

Section: Discussionmentioning

confidence: 99%

“…Previous trials have not evaluated suppression among viraemic patients, but have assessed the difference in maintenance of suppression between 2‐DR and 3‐DR groups . In the SWORD‐1 and SWORD‐2 trials, the 48 weeks adjusted difference in suppression maintenance between the 2‐DR (DTG + RPV) and the 3‐DR arms was −0.2% (95% CI: −3.0, 2.5) . In the SALT study, the difference in the proportion of patients with VL < 50 copies/mL between the 2‐DR (ATV/r + 3TC) and the 3‐DR (ATV/r + 2 NRTIs) arms was 5.7% (95% CI, −4.5%, 15.9%) at 48 weeks and 0.5% (95% CI: −9.9%, 11.0%) at 96 weeks .…”

Section: Discussionmentioning

confidence: 99%

“…Recent clinical trials have evaluated the efficacy of 2‐DRs containing dolutegravir (DTG) + rilpivirine (RPV) , DTG + 3TC and cabotegravir + RPV . In a pooled analysis of two open‐label multicentre phase III clinical trials of suppressed, treatment‐experienced patients, SWORD 1 and SWORD 2, DTG + RPV was non‐inferior to 3‐DRs and four‐drug regimens for virologic suppression maintenance (VL < 50 copies/mL at 48 weeks) and a low rate of virologic failures at week 100 in PLHIV who switched to DTG + RPV at randomization or at week 52 . In November 2017, this co‐formulation became the first complete treatment regimen containing only two ARV drugs to be approved by the US Food and Drug Administration .…”

Section: Introductionmentioning

confidence: 99%

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Two‐drug antiretroviral regimens: an assessment of virologic response and durability among treatment‐experienced persons living with HIV in the OPERA^® Observational Database

Pierone

Henegar

Fusco³

et al. 2019

J Intern AIDS Soc

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Introduction Two‐drug regimens (2‐DR) have the potential to be a viable solution to the challenges of treatment complexity, cost, adverse effects and contraindications. We sought to describe the real‐world use and effectiveness of 2‐DR among persons living with HIV (PLHIV) in the United States. Methods We analysed data for 10,190 treatment‐experienced patients from the OPERA® Observational Database initiating a new 2‐DR or three‐drug regimen (3‐DR) between 1 January 2010 and 30 June 2016. Multivariate Cox Proportional Hazards models were used to estimate the association among 2‐DR or 3‐DR initiation and virologic suppression (viral load (VL) <50 copies/mL), virologic failure (2 VLs > 200 copies/mL or 1 VL > 200 copies/mL + discontinuation) or regimen discontinuation. Results Patients initiating a 2‐DR (n = 1337, 13%) were older, and more likely to have a lower CD4 count, a history of AIDS and comorbid conditions than patients initiating a 3‐DR. There was no difference between groups in time to virologic suppression (aHR: 1.00 (95% CI: 0.88, 1.13)) among viraemic patients (baseline VL ≥ 50 copies/mL, n = 4180), or time to virologic failure (aHR: 1.15 (95% CI: 0.90, 1.48)) among virologically stable patients (baseline VL < 50 copies/mL, n = 6010). However, time to discontinuation was shorter following 2‐DR than 3‐DR initiation (aHR: 1.51 (95% CI: 1.41, 1.61)). Conclusions In this large cohort of treatment‐experienced patients, 2‐DR prescriptions were common and more frequent among patients with significant comorbidity. Virologic response was similar, but duration of use was shorter with a 2‐DR than a 3‐DR, suggesting that 2‐DRs may be a virologically effective treatment strategy for treatment‐experienced PLHIV with existing comorbidities.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Two‐drug antiretroviral regimens: an assessment of virologic response and durability among treatment‐experienced persons living with HIV in the OPERA^® Observational Database

Pierone

Henegar

Fusco³

et al. 2019

J Intern AIDS Soc

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“… 4 Interim analyses of pooled SWORD-1 and SWORD-2 data at week 100 showed HIV-1 suppression in 89% (456/513) of participants continuing dolutegravir plus rilpivirine for 2 years (early-switch group) and in 93% (444/477) of those who switched to the 2DR after the week 48 primary endpoint (late-switch group). 5 Importantly, over this 2-year period, confirmed virologic failure occurred in 8 of 990 (1%) participants (6 over 100 weeks in the early-switch group and 2 over 48 weeks in the late-switch group) with rilpivirine resistance-associated mutations (RAMs) detected in 4 of these participants. 5 Here, we report findings from the pooled analysis of SWORD-1 and SWORD-2 at week 148 assessing long-term efficacy and safety of 2DR treatment (148 weeks for the early-switch group and 96 weeks for the late-switch group).…”

Section: Introductionmentioning

confidence: 86%

Brief Report: Durable Suppression and Low Rate of Virologic Failure 3 Years After Switch to Dolutegravir + Rilpivirine 2-Drug Regimen: 148-Week Results From the SWORD-1 and SWORD-2 Randomized Clinical Trials

Wyk

Orkin

Rubio

et al. 2020

JAIDS Journal of Acquired Immune Deficiency Syndromes

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Background: The SWORD trials showed that in participants who achieved virologic suppression taking 3-drug or 4-drug regimens, switching to the 2-drug regimen dolutegravir plus rilpivirine was noninferior in maintaining HIV-1 RNA <50 copies/mL at the week 48 primary endpoint. We present pooled week 148 analysis results from both studies. Setting: SWORD-1: 65 centers, 13 countries; SWORD-2: 60 centers, 11 countries. Methods: SWORD-1 and SWORD-2 are identical, open-label, phase III studies. Participants with screening HIV-1 RNA <50 copies/mL for ≥6 months; no prior virologic failure; and no documented resistance-associated major protease inhibitor, integrase inhibitor, nucleoside reverse transcriptase inhibitor (NRTI), or non-NRTI mutations or integrase resistance-associated substitution R263K were randomly assigned 1:1 to switch to once-daily dolutegravir 50 mg plus rilpivirine 25 mg on day 1 (early-switch group) or to continue their current antiretroviral regimen and, if virologically suppressed at week 48, switch to dolutegravir plus rilpivirine at week 52 (late-switch group) until week 148. Results: Using snapshot algorithm at week 148, 432 of 513 (84%) early-switch participants (148 weeks of exposure) and 428 of 477 (90%) late-switch participants (96 weeks of exposure) maintained HIV-1 RNA <50 copies/mL. Eleven participants (1%) on dolutegravir plus rilpivirine met the confirmed virologic withdrawal criterion through week 148 (early-switch group, n = 8; late-switch group, n = 3) with no integrase resistance identified. Non-NRTI resistance-associated mutations were identified in 6 participants (<1%). Drug-related adverse events (grades 2–4) were observed in 31 (6%) early-switch and 16 (3%) late-switch participants. Significant improvements in bone biomarkers were observed. Significant improvements were observed in renal biomarkers in participants taking tenofovir disoproxil fumarate pre‐switch. Conclusion: Switching to the 2-drug regimen dolutegravir plus rilpivirine maintained virologic suppression for a high proportion of participants through 3 years, with low rates of virologic failure and a well-tolerated safety profile.

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“…articolo originale Nonostante le limitazioni indicate, anche legate al piccolo numero di pazienti inclusi, è importante evidenziare la mancanza di informazioni recenti su PLWHIV nel setting di tipo intensivo. Questo dato è, ragionevolmente, da ritenersi mutato rispetto al passato, soprattutto alla luce dell'aumento dell'aspettativa di vita di questi pazienti (1) grazie a nuovi approcci terapeutici quali l'avvio della ART, alla diagnosi di infezione di HIV (11) e la riduzione della tossicità a lungo termine di quest'ultima, per esempio con l'introduzione nella pratica clinica delle dual-therapies (13,14). Riteniamo dunque opportuno approfondire le caratteristiche dell'attuale popolazione di pazienti con infezione da HIV anche in questo setting mediante una raccolta dati prospettica e multicentrica.…”

Section: Discussioneunclassified

Cause di ricovero ed outcome del paziente con infezione da HIV nei reparti di terapia intensiva.

Berruti¹,

Sarteschi²,

Pincino³

et al. 2019

JHA

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Cause di ricovero ed outcome del paziente con infezione da HIV nei reparti di terapia intensiva. Admission and outcome of HIV-infected patients in intensive care unit. Introduzione Dall'introduzione della terapia antiretrovirale di combinazione (cART) ad oggi, la prognosi quoad vitam e la qualità di vita dei pazienti che vivono con l'infezione da HIV (people living with HIV, PLWHIV) è migliorata drasticamente. (1-3) Nonostante gli enormi progressi ottenuti, una piccola percentuale di pazienti necessita di particolari

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Efficacy and safety of dolutegravir–rilpivirine for maintenance of virological suppression in adults with HIV-1: 100-week data from the randomised, open-label, phase 3 SWORD-1 and SWORD-2 studies

Cited by 99 publications

References 18 publications

Two‐drug antiretroviral regimens: an assessment of virologic response and durability among treatment‐experienced persons living with HIV in the OPERA^® Observational Database

Two‐drug antiretroviral regimens: an assessment of virologic response and durability among treatment‐experienced persons living with HIV in the OPERA^® Observational Database

Brief Report: Durable Suppression and Low Rate of Virologic Failure 3 Years After Switch to Dolutegravir + Rilpivirine 2-Drug Regimen: 148-Week Results From the SWORD-1 and SWORD-2 Randomized Clinical Trials

Cause di ricovero ed outcome del paziente con infezione da HIV nei reparti di terapia intensiva.

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Efficacy and safety of dolutegravir–rilpivirine for maintenance of virological suppression in adults with HIV-1: 100-week data from the randomised, open-label, phase 3 SWORD-1 and SWORD-2 studies

Cited by 99 publications

References 18 publications

Two‐drug antiretroviral regimens: an assessment of virologic response and durability among treatment‐experienced persons living with HIV in the OPERA® Observational Database

Two‐drug antiretroviral regimens: an assessment of virologic response and durability among treatment‐experienced persons living with HIV in the OPERA® Observational Database

Brief Report: Durable Suppression and Low Rate of Virologic Failure 3 Years After Switch to Dolutegravir + Rilpivirine 2-Drug Regimen: 148-Week Results From the SWORD-1 and SWORD-2 Randomized Clinical Trials

Cause di ricovero ed outcome del paziente con infezione da HIV nei reparti di terapia intensiva.

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Two‐drug antiretroviral regimens: an assessment of virologic response and durability among treatment‐experienced persons living with HIV in the OPERA^® Observational Database

Two‐drug antiretroviral regimens: an assessment of virologic response and durability among treatment‐experienced persons living with HIV in the OPERA^® Observational Database