PENTA 20 (Odyssey)

19

Feb, 2021

ODYSSEY clinical trial design: a randomised global study to evaluate the efficacy and safety of dolutegravir-based antiretroviral therapy in HIV-positive children, with nested pharmacokinetic sub-studies to evaluate pragmatic WHO-weight-band based dolutegravir dosing

Tags: , ,

Authors: Cecilia L. Moore, Anna Turkova , Hilda Mujuru , Adeodata Kekitiinwa, Abbas Lugemwa, Cissy M. Kityo, Linda N. Barlow-Mosha, et al, ODYSSEY trial team

Published in: BMC Infectious Diseases

 

Background: Dolutegravir (DTG)-based antiretroviral therapy (ART) is highly effective and well-tolerated in adults and is rapidly being adopted globally. We describe the design of the ODYSSEY trial which evaluates the efficacy and safety of DTG-based ART compared with standard-of-care in children and adolescents. The ODYSSEY trial includes nested pharmacokinetic (PK) sub-studies which evaluated pragmatic World Health Organization (WHO) weight-band-based DTG dosing and opened recruitment to children < 14 kg while dosing was in development.

Methods: ODYSSEY (Once-daily DTG based ART in Young people vS. Standard thErapY) is an open-label, randomised, non-inferiority, basket trial comparing the efficacy and safety of DTG + 2 nucleos(t) ides (NRTIs) versus standard-of-care (SOC) in HIV-infected children < 18 years starting first-line ART (ODYSSEY A) or switching to second-line ART (ODYSSEY B). The primary endpoint is clinical or virological failure by 96 weeks.

Results: Between September 2016 and June 2018, 707 children weighing ≥14 kg were enrolled; including 311 ARTnaïve children and 396 children starting second-line. 47% of children were enrolled in Uganda, 21% Zimbabwe, 20% South Africa, 9% Thailand, 4% Europe. 362 (51%) participants were male; median age [range] at enrolment was 12.2 years [2.9–18.0]. 82 (12%) children weighed 14 to < 20 kg, 135 (19%) 20 to < 25 kg, 206 (29%) 25 to < 35 kg, 284 (40%) ≥35 kg. 128 (18%) had WHO stage 3 and 60 (8%) WHO stage 4 disease. Challenges encountered include: (i) running the trial across high- to low-income countries with differing frequencies of standard-of-care viral load monitoring; (ii) evaluating pragmatic DTG dosing in PK sub-studies alongside FDA- and EMA-approved dosing and subsequently transitioning participants to new recommended doses; (iii) delays in dosing information for children weighing 3 to < 14 kg and rapid recruitment of ART-naïve older/heavier children, which led to capping recruitment of participants weighing ≥35 kg in ODYSSEY A and extending recruitment (above 700) to allow for ≥60 additional children weighing between 3 to < 14 kg with associated PK; (iv) a safety alert associated with DTG use during pregnancy, which required a review of the safety plan for adolescent girls.

Conclusions: By employing a basket design, to include ART-naïve and -experienced children, and nested PK substudies, the ODYSSEY trial efficiently evaluates multiple scientific questions regarding dosing and effectiveness of DTG-based ART in children.

Read

14

Nov, 2019

EPIICAL data on Journal of AIDS: treat early, suppress fast!

Tags: ,

Treat early, suppress fast!

In a new paper just published online in Journal of AIDS, EPIICAL researchers investigated the association between the timing of antiretroviral therapy (ART) initiation and time-to suppression​ among HIV-infected infants who initiated​ ART within the first 28 days of life.

The study showed as children treated within 7 days of life have a faster​ time to viral suppression, which may result in a favorable ​impact on the viral reservoir.

These data strongly support the potential benefits of starting ART within 7 days of birth even in comparison to​ starting from 8 to 28 days after birth.

 

17

Sep, 2019

Penta HIV 1st and 2nd Line Antiretroviral Treatment Guidelines 2019

Tags: , ,

“The new updated edition of the Penta guidelines to support the use of ARVs in children is an essential contribution to paediatric patient care. Huge thanks to all those who participated in and led this work.” – Carlo Giaquinto

We are pleased to report that the 2019 Penta guidelines for first and second line antiretroviral treatment are now available. The aim of these guidelines is to provide an update to previous versions and are intended to guide antiretroviral choices for children and adolescents with perinatally acquired HIV in the European region.

The guidance will be updated at regular intervals by the Penta guidelines writing group or as significant new data or evidence becomes available.

You can download the guidelines here.

NEWSLETTER

We would like to update you on our recent activities