• DNDi-20_Logo_No-Tagline_EN_Full Colour
  • Our work
    • Diseases
      • Sleeping sickness
      • Visceral leishmaniasis
      • Cutaneous leishmaniasis
      • Chagas disease
      • Filaria: river blindness
      • Mycetoma
      • Paediatric HIV
      • Cryptococcal meningitis
      • Hepatitis C
      • Dengue
      • COVID-19
      • Antimicrobial resistance
    • Research & development
      • R&D portfolio & list of projects
      • Drug discovery
      • Translational research
      • Clinical trials
      • Registration & access
      • Treatments delivered
    • Advocacy
      • Open and collaborative R&D
      • Transparency of R&D costs
      • Pro-access policies
  • Networks & partners
    • Partnerships
      • Our partners
      • Partnering with us
    • Global networks
      • Chagas Platform
      • HAT Platform
      • HELP Helminth Elimination Platform
      • LEAP Platform
      • redeLEISH Network
    • DNDi worldwide
      • DNDi Switzerland
      • DNDi DRC
      • DNDi Eastern Africa
      • DNDi Japan
      • DNDi Latin America
      • DNDi North America
      • DNDi South Asia/India
      • DNDi South-East Asia
      • DNDi Southern Africa
  • News & resources
    • News & stories
      • News
      • Stories
      • Statements
      • Viewpoints
      • Social media
      • eNews Newsletter
    • Press
      • Press releases
      • In the media
    • Resources
      • Scientific articles
      • Our publications
      • Videos
    • Events
  • About us
    • About
      • Who we are
      • How we work
      • Our strategy
      • Our donors
      • Annual reports
    • Our people
      • Our leadership
      • Our governance
      • Contact us
    • Work with us
      • Working at DNDi
      • Job opportunities
      • Requests for proposal
  • Donate
  • DNDi-20_Logo_No-Tagline_EN_Full Colour
  • Our work
    • Diseases
      • Sleeping sickness
      • Visceral leishmaniasis
      • Cutaneous leishmaniasis
      • Chagas disease
      • Filaria: river blindness
      • Mycetoma
      • Paediatric HIV
      • Cryptococcal meningitis
      • Hepatitis C
      • Dengue
      • COVID-19
      • Antimicrobial resistance
    • Research & development
      • R&D portfolio & list of projects
      • Drug discovery
      • Translational research
      • Clinical trials
      • Registration & access
      • Treatments delivered
    • Advocacy
      • Open and collaborative R&D
      • Transparency of R&D costs
      • Pro-access policies
  • Networks & partners
    • Partnerships
      • Our partners
      • Partnering with us
    • Global networks
      • Chagas Platform
      • HAT Platform
      • HELP Helminth Elimination Platform
      • LEAP Platform
      • redeLEISH Network
    • DNDi worldwide
      • DNDi Switzerland
      • DNDi DRC
      • DNDi Eastern Africa
      • DNDi Japan
      • DNDi Latin America
      • DNDi North America
      • DNDi South Asia/India
      • DNDi South-East Asia
      • DNDi Southern Africa
  • News & resources
    • News & stories
      • News
      • Stories
      • Statements
      • Viewpoints
      • Social media
      • eNews Newsletter
    • Press
      • Press releases
      • In the media
    • Resources
      • Scientific articles
      • Our publications
      • Videos
    • Events
  • About us
    • About
      • Who we are
      • How we work
      • Our strategy
      • Our donors
      • Annual reports
    • Our people
      • Our leadership
      • Our governance
      • Contact us
    • Work with us
      • Working at DNDi
      • Job opportunities
      • Requests for proposal
  • Donate
Home > News

World AIDS Day 2015: Paediatric HIV projects update from the team

Home > News

World AIDS Day 2015: Paediatric HIV projects update from the team

Paediatric HIV Advocacy Toolkit
Paediatric HIV Advocacy Toolkit
1 Dec 2015
Share on twitter
Share on facebook
Share on linkedin
Share on email
Share on print

At the close of 2015, we would like to take this opportunity to update you on the status of DNDi’s paediatric HIV 4-in-1 formulation development programme.

DNDi’s research and development (R&D) programme aims to develop two improved child-friendly lopinavir/ritonavir (LPV/r)-based fixed dose combinations (4-in-1s) and develop a strategy to counteract the negative drug-drug interaction between lopinavir/ritonavir (LPV/r) and rifampicin during TB/HIV co-infection in children.

In 2011, we began to explore various formulation options, including prodrugs of LPV and RTV, nanosuspension and nanoparticles of LPV and RTV as well as LPV/r pellets developed by Cipla Ltd in collaboration with partners (MRC and clinical trial sites in Uganda), tested in the CHAPAS-2 study. The CHAPAS 2 results demonstrated good bioavailability of the LPV/r pellets in comparison with LPV/r syrup in children less than one year old, as well as in comparison with AbbVie’s heat stable LPV/r tablets in children aged four and above. The acceptability of the LPV/r pellets was good in the younger cohort but taste remained an issue with the older cohort. Based on these results, DNDi decided to support an additional comparative bioavailability and acceptability study of the pellets versus the liquid formulation in children aged one to four years old. Nonetheless, the LPV/r pellets still represent an improvement over the liquid formulation because they are heat stable, do not contain alcohol and other toxic excipient, are logistically easier to manage, dose, and administer.

The dossier of LPV/r pellets was submitted by Cipla Ltd. to the US Food and Drug Administration (US FDA) in 2013 and received US FDA tentative approval in May 2015.

Due to the urgency to use a better adapted formulation of LPV/r for the treatment of infants and young children in resource limited settings, DNDi decided to introduce Cipla’s LPV/r pellets in the field through implementation studies in various countries. The focus is on assessing acceptability of the formulation (ease of administration, instructions for use across different age groups, acceptability by children, caregivers, and healthcare workers) and the feasibility of using it in real life settings. These studies will provide early access to the pellets and knowledge gained will be important for treatment scale up at the country level, adoption by programs and faster product registration. The trial has started in Kenya, and we plan to extend it as soon as possible to several additional countries. The aim is for the study to support and help to accelerate the registration process, including through the WHO Prequalification Programme. It equally aims to support change of policy/treatment guidelines at country level.

In the meantime, DNDi continues its collaboration with Cipla Ltd. on improving the taste-masking of solid formulations of LPV/r and to combine LPV/r with two NRTI pairs (AZT/3TC or 3TC/ABC) in a single dosage form (fixed dose combination). Cipla Ltd. is responsible for the pharmaceutical development work (formulation screening, process development and analytics), product registration and conduct of Phase I, healthy human volunteer bioavailability studies, while DNDi manages clinical development including the implementation studies referred to above, using the LPV/r pellets developed by Cipla Ltd. While these studies provide early access to the pellets, they will be switched to the 4-in-1 formulations as soon as they are available.

A first Phase I study using a well taste masked LPV/r granules formulation was performed in healthy human volunteers in 2013. You may remember that this study showed a very large variability of Cmax and AUC’s as well as low bioavailability, approximately half of that of the reference LPV/r syrup.

The challenges of working with LPV and RTV are well-known. These molecules are highly insoluble, lipophilic and do not cross the gastro-intestinal barrier easily (Biopharmaceutical Class IV). The individual active ingredients interact with each other and with the transport and metabolism enzymes of the gut and the liver. They taste very bitter thus cannot be made into a dispersible tablet and require melt extrusion technology to enhance solubility.

Following these Phase I results, DNDi and Cipla Ltd. teams decided to evaluate different formulations of LPV/r focusing on bioavailability, stability and taste masking before moving forward to human studies. Various taste-masked granule formulations were tested while keeping coated LPV/r pellet formulations as backup options. A series of about 40 LPV/r formulations were tested in pre-clinical models to confirm bioavailability before proceeding to Phase I studies.

As of November 2015, six taste masked LPV/r formulations have been identified which could demonstrate good bioavailability. The quality of the taste masking needs to be confirmed for a few of the formulations. Three LPV/r formulations have already been tested in Phase I studies in comparison with the reference LPV/r syrup. The results showed high bioavailability of all three formulations compared to the LPV/r syrup.

This is where we are today, and are in the process of selecting the most promising formulation for further development. While the plan is to immediately switch out the ARVs currently being tested in the implementation studies to introduce the 4-in-1s, we may have to conduct a Phase II/III before being able to file for their registration.

We have also progressed on the super boosting strategy by which extra RTV is added to the existing LPV/r formulation to achieve a 1:1 ratio between LPV and RTV during TB treatment containing rifampicin was based on scant data and needed to be validated. DNDi worked with investigators from South Africa to design a pharmacokinetic study involving 90 children with the objective to show that under super boosting, LPV/r levels are similar to those obtained after HIV/TB co-therapy. Recruitment into the study commenced in January 2013 and an interim analysis was performed in 2015 and presented at a Paediatric HIV Workshop held in Vancouver in July 2015. While we still need to complete the analysis, interim results were very encouraging. We are currently completing the follow-up and analysis of this study, and plan to conduct a similar study using LPV/r pellets from Cipla Ltd. and ritonavir oral powder from AbbVie in South Africa.

 

Paediatric HIV

Read, watch, share

Loading...
Young man sitting in hospital setting
News
25 Jan 2023

It’s time medical innovation reached the 1.7 billion people affected by neglected tropical diseases: World NTD Day 2023

Film Poster Voices of Leishmaniasis: Shushi from India
Videos
25 Jan 2023

Voices of leishmaniasis: Shishu from India

Child receiving treatment
News
20 Jan 2023

DNDi’s 20th year of bringing the best science for the most neglected

Child affected by dengue and her mother at their home in Bangkok, Thailand.
Stories
16 Dec 2022

2022: Six advances in neglected disease research to remember

Statements
2 Dec 2022

DNDi‘s comments on the conceptual zero draft for the consideration of the Intergovernmental Negotiating Body at INB3

Healthcare workers discussing in hospital setting
Press releases
1 Dec 2022

DNDi partners in a new NIHR-funded Global Health Research Group on HIV-associated Fungal Infections (IMPRINT)

Healthcare workers looking into microscopes
Press releases
30 Nov 2022

Acoziborole: Investigational single-dose oral treatment raises hope for elimination of sleeping sickness in Africa

Journalists talking with healthcare workers
News
23 Nov 2022

DNDi media workshops – bringing together reporters and researchers to cover neglected disease research

VIEW ALL

Help neglected patients

To date, we have delivered twelve new treatments, saving millions of lives.

Our goal is to deliver 25 new treatments in our first 25 years. You can help us get there. 

GIVE NOW
Facebook-f
Twitter
Instagram
Linkedin-in
Youtube
International non-profit developing safe, effective, and affordable treatments for the most neglected patients.

Learn more

  • Diseases
  • Neglected tropical diseases
  • R&D portfolio
  • Policy advocacy

Get in touch

  • Our offices
  • Contact us
  • Integrity Line

Support us

  • Donate
  • Subscribe to eNews

Work with us

  • Join research networks
  • Jobs
  • RFPs
  • Terms of Use   
  •   Acceptable Use Policy   
  •   Privacy Policy   
  •   Cookie Policy   
  •   Our policies   

  • Except for images, films and trademarks which are subject to DNDi’s Terms of Use, content on this site is licensed under a Creative Commons Attribution-NonCommercial-Share Alike 3.0 Switzerland License   
We use cookies to track our audience and improve our content. By clicking 'Accept All', you are agreeing to our use of cookies. Click on 'Customize' to accept only some cookies.
Customize
ACCEPT ALL
Manage consent

Privacy Overview

This website uses cookies to improve your experience while you navigate through the website. Out of these, the cookies that are categorized as necessary are stored on your browser as they are essential for the working of basic functionalities of the website. We also use third-party cookies that help us analyze and understand how you use this website. These cookies will be stored in your browser only with your consent. You also have the option to opt-out of these cookies. But opting out of some of these cookies may affect your browsing experience.
Necessary
Always Enabled
Necessary cookies are absolutely essential for the website to function properly. These cookies ensure basic functionalities and security features of the website, anonymously.
CookieDurationDescription
cookielawinfo-checkbox-advertisement1 yearSet by the GDPR Cookie Consent plugin, this cookie is used to record the user consent for the cookies in the "Advertisement" category .
cookielawinfo-checkbox-analytics11 monthsThis cookie is set by GDPR Cookie Consent plugin. The cookie is used to store the user consent for the cookies in the category "Analytics".
cookielawinfo-checkbox-functional11 monthsThe cookie is set by GDPR cookie consent to record the user consent for the cookies in the category "Functional".
cookielawinfo-checkbox-necessary11 monthsThis cookie is set by GDPR Cookie Consent plugin. The cookies is used to store the user consent for the cookies in the category "Necessary".
cookielawinfo-checkbox-others11 monthsThis cookie is set by GDPR Cookie Consent plugin. The cookie is used to store the user consent for the cookies in the category "Other.
cookielawinfo-checkbox-performance11 monthsThis cookie is set by GDPR Cookie Consent plugin. The cookie is used to store the user consent for the cookies in the category "Performance".
CookieLawInfoConsent1 yearRecords the default button state of the corresponding category & the status of CCPA. It works only in coordination with the primary cookie.
PHPSESSIDsessionThis cookie is native to PHP applications. The cookie is used to store and identify a users' unique session ID for the purpose of managing user session on the website. The cookie is a session cookies and is deleted when all the browser windows are closed.
viewed_cookie_policy11 monthsThe cookie is set by the GDPR Cookie Consent plugin and is used to store whether or not user has consented to the use of cookies. It does not store any personal data.
Functional
Functional cookies help to perform certain functionalities like sharing the content of the website on social media platforms, collect feedbacks, and other third-party features.
CookieDurationDescription
elementorneverThis cookie is used by the website's WordPress theme. It allows the website owner to implement or change the website's content in real-time.
Analytics
Analytical cookies are used to understand how visitors interact with the website. These cookies help provide information on metrics the number of visitors, bounce rate, traffic source, etc.
CookieDurationDescription
_ga2 yearsThe _ga cookie, installed by Google Analytics, calculates visitor, session and campaign data and also keeps track of site usage for the site's analytics report. The cookie stores information anonymously and assigns a randomly generated number to recognize unique visitors.
_ga_16Q5RH3XRG2 yearsThis cookie is installed by Google Analytics.
_gat_UA-10302561-11 minuteA variation of the _gat cookie set by Google Analytics and Google Tag Manager to allow website owners to track visitor behaviour and measure site performance. The pattern element in the name contains the unique identity number of the account or website it relates to.
_gid1 dayInstalled by Google Analytics, _gid cookie stores information on how visitors use a website, while also creating an analytics report of the website's performance. Some of the data that are collected include the number of visitors, their source, and the pages they visit anonymously.
_hjAbsoluteSessionInProgress30 minutesHotjar sets this cookie to detect the first pageview session of a user. This is a True/False flag set by the cookie.
_hjFirstSeen30 minutesHotjar sets this cookie to identify a new user’s first session. It stores a true/false value, indicating whether it was the first time Hotjar saw this user.
_hjIncludedInPageviewSample2 minutesHotjar sets this cookie to know whether a user is included in the data sampling defined by the site's pageview limit.
_hjIncludedInSessionSample2 minutesHotjar sets this cookie to know whether a user is included in the data sampling defined by the site's daily session limit.
_hjSession_112884430 minutesHotjar sets this cookie.
_hjSessionUser_11288441 yearHotjar sets this cookie.
CONSENT2 yearsYouTube sets this cookie via embedded youtube-videos and registers anonymous statistical data.
Targeting
Advertisement cookies are used to provide visitors with relevant ads and marketing campaigns. These cookies track visitors across websites and collect information to provide customized ads.
SAVE & ACCEPT
Powered by CookieYes Logo