Publications

30

Aug, 2019

Dolutegravir pharmacokinetics during pregnancy and postpartum

 

Authors: Colbers A, Bollen P, Freriksen J, Konopnicki D, Weizsäcker K, Hidalgo Tenorio C, Moltó J, Taylor G, Alejandre I,  van Crevel R, Burger D; on behalf of the PANNA network

Published: 26th Conference on Retroviruses and Opportunistic Infections, March 4th – 7th, 2019– Seattle. P_758.

 

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30

Aug, 2019

Dolutegravir pharmacokinetics during pregnancy and postpartum

 

Authors: Colbers A, Bollen P, Freriksen J, Konopnicki D, Weizsäcker K, Hidalgo Tenorio C, Moltó J, Taylor G, Alejandre I,  van Crevel R, Burger D.

Published: Oral presentation at 9th edition of the International Workshop on HIV & Women, March 2nd-3rd 2019, Seattle

 

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30

Aug, 2019

Efavirenz pharmacokinetics during pregnancy and infant washout

 

Authors: Kreitchmann R, Schalkwijk S, Best B, et al.

Published in: Antivir Ther. 2019;24(2):95-103

Background Limited data exist on efavirenz pharmacokinetics in HIV-positive pregnant women and neonatal washout.

Methods HIV-infected pregnant women receiving 600 mg efavirenz once daily had intensive steady-state 24-h pharmacokinetics profiles during the second trimester (2T), third trimester (3T) and 6-12 weeks postpartum (PP). Maternal and umbilical cord blood samples were drawn at delivery and neonatal washout pharmacokinetics were determined. Therapeutic targets were the estimated 10th percentile efavirenz area under the concentration-time curve (AUC) in non-pregnant historical controls (40.0 μg•h/ml) and a trough concentration (C24 h) of 1 μg/ml. Data were prospectively collected within two trials: IMPAACT P1026s (United States) and PANNA (Europe).

Results Among 42 women studied, 15, 42 and 40 had efavirenz pharmacokinetic data available in 2T, 3T and PP, respectively. Median (range) 3T age 33 (20.7-43.5) years, weight 74 (50-132) kg and gestational age 33.4 (28.4-37.9 weeks). Efavirenz AUC during the 3T (60 μg•h/ml) was similar to that reported in non-pregnant adults (58 μg•h/ml). Exposure in the 2T was lower, but within the 0.80-1.25 range. C24concentrations during pregnancy were lower compared to historical controls on 600 mg efavirenz, however, they were similar to the C24concentrations after equally potent dose of 400 mg efavirenz. Cord blood/maternal plasma concentration ratio (range) was 0.67 (0.36-0.95). Among 23 infants with washout data available, median (interquartile range) elimination half-life was 65.6 h (40.6-129). HIV RNA viral loads at delivery were <400 and <50 copies/ml for 96.7% and 86.7% of women, respectively. In 3T and PP, respectively, 8/41 (19%) and 6/40 (15%) had AUC below target; 7/41 (17%) and 3/39 (8%) had C24 below target.

Conclusions Efavirenz exposure was similar during pregnancy compared with PP, C24 was in line with C24 after 400 mg equipotent efavirenz dosing. Efavirenz readily crossed the placenta and infant elimination half-life was over twice that of maternal participants.

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30

Aug, 2019

Evaluating darunavir/ritonavir dosing regimens for HIV-positive pregnant women using semi-mechanistic pharmacokinetic modelling

 

Authors: Schalkwijk S, Ter Heine R, Colbers A, et al.

Published in: J Antimicrob Chemother. 2019;30 [Epub ahead of print]

Background Darunavir 800 mg once (q24h) or 600 mg twice (q12h) daily combined with low-dose ritonavir is used to treat HIV-positive pregnant women. Decreased total darunavir exposure (17%-50%) has been reported during pregnancy, but limited data on unbound exposure are available.

Objectives To evaluate total and unbound darunavir exposures following standard darunavir/ritonavir dosing and to explore the value of potential optimized darunavir/ritonavir dosing regimens for HIV-positive pregnant women.

Patients and Methods A population pharmacokinetic analysis was conducted based on data from 85 women. The final model was used to simulate total and unbound darunavir AUC0-τ and Ctrough during the third trimester of pregnancy, as well as to assess the probability of therapeutic exposure.

Results Simulations predicted that total darunavir exposure (AUC0-τ) was 24% and 23% lower in pregnancy for standard q24h and q12h dosing, respectively. Unbound darunavir AUC0-τ was 5% and 8% lower compared with post-partum for standard q24h and q12h dosing, respectively. The probability of therapeutic exposure (unbound) during pregnancy was higher for standard q12h dosing (99%) than for q24h dosing (94%).

Conclusion The standard q12h regimen resulted in maximal and higher rates of therapeutic exposure compared with standard q24h dosing. Darunavir/ritonavir 600/100 mg q12h should therefore be the preferred regimen during pregnancy unless (adherence) issues dictate q24h dosing. The value of alternative dosing regimens seems limited.

22

Aug, 2019

CUAMM workshop: “Implementation Research in resource limited countries”

 

Our close collaborators, Doctors with Africa CUAMM, are hosting the workshop “Implementation Research in resource limited countries” on 30 September – 3 October in Padua, Italy.

Implementation research is a growing field of study with roots in many disciplines and research traditions. Its core intent is to understand not only what is and isn’t working, but how and why implementation is going right or wrong, and testing approaches to improve it. Implementation research is particularly important in global health because it takes what we know and turns it into what we do, addressing challenges in diverse real-world settings and the practicalities of achieving national and global health goals. This type of research uses multiple disciplines and methods and emphasises partnerships between community members, implementers, researchers, and policy makers.

The dynamic 4-day event will bring together an extensive group of experts involved in different areas of clinical research and capacity-building. The workshop is aimed at graduates, post-graduates and doctoral students in the field of healthcare, or similar professional figures interested in exploring the aspects of operational research in this area. Theoretical training will be accompanied by an experiential part (to present the research carried out by Doctors with Africa CUAMM or by other bodies in countries with limited resources) and practical exercises. Participating from Penta is Carlo Giaquinto, who has been invited to give the following presentation: “International Research Agenda on Infectious Diseases: the international agenda”. Other notable talks deal with key topics such as ‘Theory of Change‘, funding priorities and opportunities, and international research agendas on nutrition, chronic diseases, mental health and disabilities.

Founded in 1950, CUAMM was the first non-governmental organization focused on healthcare to be recognized by the Italian government. It is now the country’s leading organization working to protect and improve the wellbeing and health of vulnerable communities in Sub-Saharan Africa. The organization carries out capacity-building activities and conducts and disseminates scientific research with the end goal of ensuring that the fundamental human right to health can be enjoyed by everyone everywhere. Working with international and local partner teams, CUAMM provides medical aid and expertise in 8 African countries: Angola, Central African Republic, Ethiopia, Mozambique, Sierra Leone, South Sudan, Tanzania, Uganda.

The course is free of charge. To register send your updated CV to Chiara Cavagna (c.cavagna@cuamm.org) by 3 September. In the case of too many applications, a selection of participants will be made.

The programme (Italian) is available here!

12

Aug, 2019

Penta ID Network Meeting 2019 – a look back in pictures!

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Following the great success of the recent Penta ID Network Meeting, we are pleased to now share with you a photo gallery of the event.

On 30th June, 234 participants from 31 countries around the world gathered together in the beautiful setting of Baveno, Italy for the biannual ‘PIM’ – Penta ID Network Meeting. Marked by 3 days of scientific discussion, sharing ideas and opening up new channels of collaboration, this year’s event was brimming with activity.

The very first ‘PIM’ meeting took place back in 1999, when Penta was an ambitious young European network with a main focus on HIV research. In recent years we have grown and developed into a truly global workforce, now operating in many different areas – including HIV, Antimicrobial resistance, Arboviruses, Paediatric medicines, and Education and training. “The diversity is so obvious, the new scientific organisation is fantastic, building bridges to continue the mission of Penta across the world”, in the words of Penta Scientific Chief Officer, Theoklis Zaoutis.

PIM 2019 was an opportunity to solidify existing partnerships. With GARDP we have a global platform on antibiotics for the paediatric population. Together, we can accelerate paediatric development of antibiotic treatments and tackle drug-resistant infections in children. “We have a lot of work to do, but we are moving in the right direction” – Manica Balasegaram, Executive Director, GARDP.

Moreover, this new edition of the PIM was an opportunity to reflect on the real impact of what we are doing. A special thanks to Siobhan Crowley for her thought-provoking words, which encouraged us to “communicate, inspire and empower, take initiative and believe in the transformational power of your work”.

We are very excited to be moving forward with so many new projects and studies, continuing the Penta spirit of sharing… as a value, a method, and a goal.

“Thank you to everyone for joining us. Penta is really ‘you’, and our success is through your commitment!” – Carlo Giaquinto

Enjoy the full photo gallery here!

9

Aug, 2019

‘Prescribing Medicines for Children’: new international textbook published

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We are pleased to report that the book ‘Prescribing Medicines for Children: From drug development to practical administration’ has been launched. Co-edited by our friends Prof. Mike Sharland (Penta Foundation Board Member) and Prof. Mark Turner, in collaboration with Charlotte Barker, the textbook aims to improve understanding in all aspects of paediatric prescribing, from the development of suitable drugs through to their practical administration.

The international textbook is uniquely placed as it covers different key clinical prescribing areas. To date, there has been no other manual collecting the prinicples of safe and effective prescribing related to all paediatric sub-specialties. It provides accurate and concise guidance on the principles behind optimal neonatal and paediatric prescribing. Highlights include the differences in prescribing habits between countries and the shared principles that underpin rational prescribing in paediatrics and neonatology. Thus, it can be used as a quick reference guide essential for paediatricians and primary care physicians, pharmacists, nurses, academic scientists, and those working in the pharmaceutical industry and drug regulation.

The book stems from the EU-funded Global Research in Paediatrics (GRiP) project, which aimed to stimulate the development and safe use of medicines for children. It harnesses this international expertise, to facilitate the translation of essential pharmacological principles into good prescribing practice.

Prescribing Medicines for Children is one of the most remarkable outputs of the GRiP project. It is going to be a unique tool to deliver safe and effective medicines for infants and children” – Carlo Giaquinto

You can find the book for sale online here.

8

Aug, 2019

SMILE: Enrolment target of 300 patients achieved today!

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We are thrilled to bring you the news that the Penta-sponsored clinical trial, SMILE, has hit its enrolment target with the recruitment of its 300th patient. The patient was enrolled at the Kryvyi Rih Hospital in Ukraine. This wonderful result has been achieved through the continued hard work, commitment and cooperation among the sites, the clinical trial units and the sponsor.

SMILE (also known as PENTA 17) stands for “Strategy for Maintenance of HIV suppression with once daiLy Integrase inhibitor + darunavir/ritonavir in childrEn”. It is a multicentre randomised study evaluating safety and antiviral effect of a once daily integrase inhibitor administered with darunavir/ritonavir compared to standard of care among HIV-1 infected, virologically suppressed paediatric participants. Participants from 32 sites spread across 11 countries in Europe, Asia, Africa and South America have taken part in the study. All participants will be followed up for a minimum of 48 weeks until the last participant enrolled reaches 48 weeks of follow-up.

Our congratulations and thanks to the participants and families, the clinicians and sites involved as well as the clinical trial units of the study, INSERM-SC10, MRC-CTU at UCL and PHPT for your ongoing collaboration! We also extend a very special thank you to the Chief Investigator of the trial, Prof. José Tomas Ramos Amador and the Clinical Project Officer, Dr. Alexandra Compagnucci and and her team.

The trial is supported by Janssen Pharmaceutica and ViiV Healthcare. The IMPs Prezista (DRV) and Tivicay (DTG) are provided by the companies respectively.

 

* Photo credits: Bruno Glätsch at Pixabay

NEWSLETTER

We would like to update you on our recent activities