N - Unitaid | Paediatric HIV

2020 HIV DIAGNOSTICS

19. Continue supporting the pediatric diagnostic agenda as per the Plan of Action through implementing partners (including, for year 2021, CHAI) and WHO’s Prequalification Program and WHO HIV/Hepatitis/STIs department.

20. Further generate evidence on optimal deployment models, impact and cost-effectiveness of new and existing technologies.

21. Support optimal use of technologies across different laboratory tiers and disease areas (including integration with TB and coinfections/comorbidities services).

22. Support further discussions with manufacturers of relevant diagnostics products to optimize pricing and supply terms towards affordable and accessible options.

Updates

June 2022

Unitaid’s flagship investment in Early Infant Diagnosis was closed in Q4 2021, however, Unitaid continues to support the pediatric diagnostic agenda as per the Plan of Action through support for WHO’s Prequalification Program and WHO HIV/Hepatitis/STIs department by:
- Support through the WHO Enabler grants for on-going technical and/or implementation guidance on HIV Dx – this includes the upcoming 2022 WHO-hosted “Synergy Meeting” on diagnostics which will focus on integration of molecular diagnostics, and ensuring the disruptions from COVID-19 are minimized.
- Investments made in 2021 and 2022 for COVID-19 molecular diagnostics and the optimization of diagnostic networks in country to ensure minimal disruptions to EID testing and optimal use of centralized and POC molecular capacity
- Supporting enabling activities to ensure the optimal use of technologies across different laboratory tiers and disease areas (including integration with TB and coinfections/comorbidities services).
- Supporting further discussions with manufacturers of relevant diagnostics products to optimize pricing and supply terms towards affordable and accessible options, in particular through ongoing work of the Integrated Diagnostics Consortium

March 2022

Unitaid’s flagship investment in Early Infant Diagnosis was closed in Q4 2021, however, Unitaid continues to support the pediatric diagnostic agenda as per the Plan of Action through support for WHO’s Prequalification Program and WHO HIV/Hepatitis/STIs department by:

Investments made in 2021 and 2022 for COVID-19 molecular diagnostics and the optimization of diagnostic networks in country to ensure minimal disruptions to EID testing
Supporting enabling activities to ensure the optimal use of technologies across different laboratory tiers and disease areas (including integration with TB and coinfections/comorbidities services).
Supporting further discussions with manufacturers of relevant diagnostics products to optimize pricing and supply terms towards affordable and accessible options., in particular through ongoing work of the Integrated Diagnostics Consortium

2018 HIV DIAGNOSTICS

12. Discourage and refrain from funding national evaluation studies that would be duplicative of studies done for WHO PQ listing or SRA approval.

13. Fund impactful technologies and interventions quickly.

14. Support in a transparent manner the procurement of commodities and operational costs to maintain and further scale-up POC EID, as well as viral load testing for infants, children, and pregnant and breastfeeding women, as an integral part of optimized and integrated national laboratory networks and in accordance with national EID and VL plans and targets.

15. Support the development of a competitive, healthy, and sustainable market for POC and laboratory technologies.

16. Continue to support WHO PQ to shorten timelines for dossier review and minimize time to national registration.

56. Support the expansion of the WHO-led Collaborative Registration Process to diagnostics, and leverage existing projects in diagnostics to support the roll out of the procedure for key diagnostics.

57. Remove duplicative in-country performance evaluations from operational budgets of ongoing investments and grants.

58. Support implementing partners (including CHAI) to address outstanding barriers on diagnostics optimal uptake and scale.

Updates

October 2020

Commitment 56:

Unitaid continues to provide support on the WHO collaborative registration procedure (CRP) for IVDs, and the pilot has been completed for the initial molecular POC product.

Commitment 58:

Unitaid has extended funding for the CHAI/UNICEF Molecular grant to include support for COVID-19 diagnostics. This support will also ensure continuity of EID testing services in focal countries the context of the pandemic.

Commitment 12:

WHO PQ support extended; WHO enabler grant support potentially extended as well.

Commitment 14:

With CHAI and UNICEF, further directed the existing grant to support a number of laboratory network optimization exercises, including in Cameroon, DRC and Zimbabwe.

Commitment 56:

Unitaid continues to provide support on the WHO collaborative registration procedure (CRP) for IVDs, and the pilot has been completed for the initial molecular POC product.

Commitment 57:

No further support to in-country performance evaluations exists in Unitaid Dx grants.

Support to the integration event led by WHO (July 2019)

Commitment 58:

2020 TB DIAGNOSTICS

16. Support the development of a competitive, healthy, and sustainable market for point-of-care and laboratory-based testing for TB infection and disease as well as digital x-ray technologies.

17. Consider increasing investments in diagnostic research and development, case-finding, and scale-up of product procurement in high TB burden countries.

18. Support country level roll-out of new tools for pediatric TB detection, including testing of nasopharyngeal aspirates, stool, urine, and other non-sputum specimens.

19. Consider support to build evidence base for product development, evaluation, and WHO guidance.

20. Add paediatric-specific diagnostics and associated specimen collection devices/consumables to available diagnostics catalogues.

21. Include TB-LAM and other urine-based lateral flow assays in procurement considerations in all countries but especially for high HIV burden countries.

22. Support the development of pediatric X-ray libraries to facilitate the development of machine learning algorithms for the interpretation of pediatric chest X-rays.

23. Support more coordinated diagnostic network strengthening and optimization exercises, led by national governments, across diseases (TB and HIV as well as other key diagnostics).

24. Support the development of biomarker-based tests for infants and children, as well as tests and/or testing procedures that use alternative (non-sputum-based) specimens.

25. Facilitate appropriate budgeting and access to quality-assured TB diagnostics at affordable prices and ensure a sustainable market and supplier accountability.

47. Supporting the TB diagnostic agenda through our grants (TB Speed – Université de Bordeaux and all consortium members and target countries, Seq&Treat – FIND, and WHO).

48. Identify and establish effective collaboration and funding support to advance the application of new technologies for delivery of improved paediatric diagnosis, using other samples than sputum, such as stools and nasopharyngeal aspirate.

49. Promote integration of different services to increase detection and treatment of children with TB.

Updates

June 2022

Unitaid will continue to support the TB diagnostic agenda through our grants (TB Speed – Université de Bordeaux and all consortium members and target countries, Seq&Treat – FIND, and WHO).
Unitaid will also continue to identify and establish effective collaboration and funding support to advance the application of new technologies for delivery of improved paediatric diagnosis, using other samples than sputum, such as stools and nasopharyngeal aspirate and promote integration of different services to increase detection and treatment of children with TB.
A call for proposals for Accelerating tools to drive TB detection was launched in 2021. The call attracted many applications with 2 candidates selected for awards in TB Diagnostics over a period of 3 years, commencing in 2022.Contracting procedures are under way and implementation is expected to kick off in the coming months.

March 2022

Unitaid will continue to support the TB diagnostic agenda through our grants (TB Speed – Université de Bordeaux and all consortium members and target countries, Seq&Treat – FIND, and WHO).
Unitaid will also continue to identify and establish effective collaboration and funding support to advance the application of new technologies for delivery of improved paediatric diagnosis, using other samples than sputum, such as stools and nasopharyngeal aspirate and promote integration of different services to increase detection and treatment of children with TB.
A call for proposals for Accelerating tools to drive TB detection was launched in 2021. The call attracted many applications with 2 candidates selected for awards in TB Diagnostics over a period of 3 years, commencing in 2022. Contracting procedures are under way and implementation is expected to kick off in the coming months.

October 2021

Unitaid will continue to support the TB diagnostic agenda through our grants (TB Speed – Université de Bordeaux and all consortium members and target countries, Seq&Treat – FIND, and WHO) and through planned investments in the area of TB detection through a call of proposals that closed May 24th.
Identify and establish effective collaboration and funding support to advance the application of new technologies for delivery of improved paediatric diagnosis, using other samples than sputum, such as stools and nasopharyngeal aspirate
Promote integration of different services to increase detection and treatment of children with TB.

April 2021

Unitaid will continue to support the TB diagnostic agenda through our grants (TB Speed – Université de Bordeaux and all consortium members and target countries, Seq&Treat – FIND, and WHO) and through planned investments in the area of TB detection through a newly launched RFP (24th March 2021) to:
- Identify and establish effective collaboration and funding support to advance the application of new technologies for delivery of improved paediatric diagnosis, using other samples than sputum, such as stools and nasopharyngeal aspirate
- Promote integration of different services to increase detection and treatment of children with TB.

2020 HIV TREATMENT

16. Continue supporting the paediatric agenda as per the Plan of Action through the grants with different partners (including, for year 2021, CHAI, EGPAF, Medicines Patent Pool, Research- institutions such as University of Liverpool or Stellenbosch, WHO’s Prequalification Program and WHO HIV/Hepatitis/STIs department).

17. Identify and establish effective collaboration and funding support to advance the application of new technologies for delivery of improved pediatric formulations.

18. Support GAP-f partners’ plan for the accelerated introduction and rollout of the generic DTG 10mg dispersible tablet formulation in 13 priority countries.

19. Provide funding for the development, regulatory review, and accelerated introduction of generic formulations of a TAF-containing pediatric FDC, in collaboration with Gilead, and advance on the work on DRV/r f and ALD pediatric formulation.

50. Support stakeholders involved in accelerated introduction and rollout of the 4-in-1 formulation as an alternative regimen for young children in priority countries.

51. Continue to support, with WHO and partners, the introduction of optimal ARV formulations, the roll out of a pediatric Advanced HIV DISEASE (AHD) package of care – including associated treatment literacy and training, and enhanced monitoring &safety data platform for new and existing paediatric ARV drugs.

Updates

June 2022

Unitaid commits to continue supporting the pediatric agenda as per the Plan of Action through the grants with different partners (including, for year 2022, CHAI, EGPAF, Medicines Patent Pool, Research- institutions such as University of Liverpool and Stellenbosch, WHO’s Prequalification Program and WHO HIV/Hepatitis/STIs department).
1. Through Unitaid/CHAI OPTIMAL grant:
- Paediatric DRV/r FDC incentive program ongoing with Laurus Labs, with bioequivalence studies currently ongoing and program on track to have a product commercialized by mid 2023.
- The generic ALD FDC is under development; bioequivalence studies of the prototype ongoing with two manufacturers, with regulatory filing expected in Q4 2022.
- Through our Optimal grant - CHAI Launched a collaboration with Gilead and PENTA to accelerate the development of generic paediatric TAF formulations, with generic supplier engagement expected after the release of PENTA study results
2. The paediatric FDC 4-in-1 formulation of ABC/3TC/LPV/r granules developed by Cipla and DnDi with Unitaid funding received SAHPRA approval on May 24, the first global regulatory approval for this product, and in South Africa, which has the largest number of children living with HIV in the world.
3. Unitaid also continues to support the paediatric ART optimization agenda through the ongoing WHO Enabler grant for technical assistance to countries, convening experts through the PAWG, PADO and other fora, as well as development of technical/normative guidance and publications.

March 2022

The RFP for the development of the paediatric DRV/r FDC was launched at the end of 2020, with Laurus Labs being selected as the manufacturer for the incentive program, with a product expected to be commercialized by mid 2023. pDRV/r press release
The ALD FDC is under development; bioequivalence studies of the prototype ongoing with two manufacturers, one concluded.
Rollout of pDTG is rapidly accelerating with widespread adoption and supportive partner guidance – 25 countries now have confirmed pDTG deliveries.
Through our Optimal grant - CHAI Launched a collaboration with Gilead and Penta to accelerate the development of paediatric TAF.

October 2021

A call for proposals for Innovative Formulation and Delivery Solutions for Children’s Medicines in Low-Resource Settings through the Unitaid Agility mechanism (Unitaid Explore) was launched at the end of 2020. The call attracted several applications with 2 candidates selected to apply innovative technologies to the development and commercialization of paediatric formulations over a period of 2 years. Contracting procedures have been concluded and selection of suitable drug candidates for development is underway in collaboration with GAP-f/WHO.
The RFP for the development of the paediatric DRV/r FDC was launched at the end of 2020, with Laurus Labs being selected as the manufacturer for the incentive program, with a product expected to be commercialized by mid 2023. pDRV /r press release
The ALD FDC is under development; bioequivalence studies of the prototype ongoing with two manufacturers, one concluded.
Paediatric DTG 10mg roll out currently on-going in 5 countries (Kenya, Uganda, Zimbabwe,Malawi, Benin )
Through our Optimal grant - CHAI Launched a collaboration with Gilead and Penta to accelerate the development of paediatric TAF. CHAI is currently working with partners to conclude the formalization of the partnership.

April 2021

A call for proposals through the Unitaid Agility mechanism (Unitaid Explore) was launched at the end of 2020, attracting several applications and leading to selection of 2 candidates to apply innovative technologies to the development and commercialization of paediatric formulations over a period of 2 years.
The RFP for the development of the DRV/r FDC was launched at the end of 2020, culminating in the selection of Laurus Labs as the manufacturer for the incentive program, with a product expected to be commercialized by mid 2023
The ALD FDC is under development, with the bioequivalence studies of the prototype currently ongoing
The first batch of 100,000 packs of paediatric DTG 10mg was ordered and should be in the first 6 countries (Kenya, Uganda, Zimbabwe, Nigeria, Malawi, Benin ) by the end of H1 2021, with Kenya expected to receive the first consignment this month

2018 HIV TREATMENT

21. Support catalytic procurement of all or part of initial validation batches from manufacturers such that product availability is not delayed once approval or tentative approval is achieved.

22. Incentivize commercialization of new pediatric ARV products “at risk” to accelerate introduction and scale up of new paediatric ARV product such that product is available at time of approval/tentative approval/prequalification.

23. Jointly agree upon and execute next steps to optimize the availability and delivery of these
formulations in 2019 including:

Timely and regular information sharing (including orders placed and timelines for deliveries)
Providing best possible demand forecasts
Collaborate on the optimization of limited supply within and among countries and joint prioritization among orders to ensure sustainable supplies to children once initiated
Support product uptake at country level
Regulatory filings as needed to support scale-up, timely responses to queries raised during the review, and implementation (re-validation as required) of post approval changes at risk during the review period.

47. Provide financial incentives for the development of child-friendly formulations for ARVs, including DTG 10 mg dispersible tablet and LPV/r fixed-dosed combinations

48. Continue to strategically support GAP-f and the relevant participation of Unitaid-partners, and engage with Unitaid Executive Board in 2019 to explore funding new investment cases for paediatric ARV optimization and access.

Updates

2017 HIV TREATMENT

Action 8: Support and fund clinical and implementation research to inform development and approval as well as use of paediatric formulations included in the PADO list.

Action 9: Only fund the procurement of drugs and formulations recommended by WHO that are included in the Optimal Formulary.

Action 21: Provide funding to support actions required for quickly introducing and scale-up new, optimal paediatric formulations.

Individual Commitment: UNITAID will continue to invest in development and rapid introduction of priority products for infants and children.

Updates

Individual Commitment:

WHO PQ support extended; WHO enabler grant support potentially extended as well. Other projects: in 2019 Unitaid is working on new targeted investments for pediatrics (research,product development, access and early product introduction), and extensions of our current commitments.

October 2020

EGPAF SPAAN has been merged into CHAI Optimal with both focusing on supporting a number of countries in the adoption of optimized pediatric ARVs, which will be available and rolled out early 2021. Further, it supports transition to more optimal regimens in view of the rapidly-evolving ARV landscape. This Unitaid-funded Optimal ARV grant has been extended to the end of December 2022.
Unitaid/CHAI launched an RFP on 14 September requesting proposals to accelerate access to Darunavir/ritonavir (DRV/r) the best-in-class second-line treatment for HIV in children aged 3 (>10kg) and older in low- and middle-income countries. RFP closes this week on 16 October.
As a result of Unitaid/CHAI collaboration, together with industry, Generic DTG 10mg with access pricing is expected to be available by the end of November 2020.
Unitaid is funding the BENEFIT kids 4-in-1 sub-study to assess the use of the new 4-in-1 formulation (ABC/3TC/LPV/r”) in HIV-exposed and infected neonates. Enrolment for the neo PK study commenced in Q3 2020.

June 2020

Adoption: UNITAID continues working with key partners (Global Fund, PEPFAR, …) and supporting WHO (including WHO HIV/STIs/Hepatitis department enabler grant and WHO PQ) and implementer grantees (EGPAF and CHAI) to support a number of countries for rapid adoption of the emerging products, including 4-in-1 (ABC/3TC/LPV/r) and DTG 10 mg, both coming to market in Q1 2021.
Product availability: UNITAID IS exploring to launch the paediatric DRV/r incentive program, implement the ALD market accelerator, and the launch of a new accelerator program for paediatric TAF-DTG. The 4in1 developed with DNDi, and the DTG10 mg dispersible generic tablet developed through the Optimal program, in collaboration with generic companies and ViiV, have now reached a key milestone with products’ submission for regulatory approval.
Evidence gaps : UNITAID supported DoLPHIN 2 clinical trial by the University of Liverpool was reprogrammed and extended to include an infant safety follow-up component, which is monitoring neuroinflammatory abnormalities among HIV-Exposed but Uninfected (HEU) infants whose mothers received ART. In addition, three of UNITAID supported clinical trials including DoLPHIN 2, ADVANCE and NAMSAL were extended to pool data with an aim to answer important safety questions around DTG use and weight gain and hyperglycaemia – this includes follow up on pregnancies with increased weight gain. UNITAID HAS a project with Stellenbosch University evaluating the use of LPV/r/ABC/3TC among HIV positive infants.
UNITAID is working closely with WHO, EGPAF and CHAI in developing a policy and a package of care for paediatric Advanced HIV Disease.

Commitments 47 & 48:

Considering reprogramming of grants for increase impact of grants to address new priorities in PADO4 and GAP-f funding situation. New projects under consideration, as well as reprogramming current ones, to increase impact of grants to address new priorities in PADO4 (targeted investments for research, product development, access and early product introduction).

The Unitaid grant to EGPAF has been reprogrammed and extended to focus on supporting a number of countries in the adoption of optimized pediatrics ARV. Further, it supports transition to more optimal regimens in view of the rapidly-evolving ARV landscape. This work builds upon the existing Unitaid-CHAI Optimal ARV grant.

A new grant from Unitaid has been approved in September 2019 to Stellenbosch University as part of the BENEFIT Kids project (Better Evidence and Formulations for Improved MDR-TB Treatment for Children). The pediatric HIV component considers the use of the 4in1 (LPV/r-ABC-3TC) among HIV-exposed neonates, exploring both safety and pharmacokinetics. The inclusion of the HIV infant study component responds directly to the research gaps identified at PADO4 in December 2018 on the use of LPV/r in this population.

The Unitaid Enabler grant to the World Health Organization has been expanded with an additional output focused to support pediatric ARV prioritization.

2020 TB TREATMENT

22. Support, strengthen, and expand clinical and implementation research to inform development, approval and use of paediatric formulations included in the priority list, including early PK modelling and palatability studies.

98. Supporting the TB treatment agenda through our grants (TB Speed – Université de Bordeaux, Cap-TB – EGPAF, Benefit Kids – Stellenbosch University, IMPAACT4TB – Aurum Institute, and WHO).

99. Identify and establish effective collaboration and funding support to advance the application of new technologies for delivery of improved paediatric formulations for TB treatment for susceptible and resistant TB.

100. Promote integration of different services to increase detection and treatment of children with TB.

101. Continue to support, with WHO and partners, the introduction of optimal paediatric formulations for treatment, and also preventive treatment (3RH and 3HP).

Updates

June 2022

Unitaid commits to continue supporting the TB treatment agenda through our grants (TB Speed – Université de Bordeaux, Cap-TB – EGPAF, Benefit Kids – Stellenbosch University, IMPAACT4TB – Aurum Institute, and WHO).
In particular we commit to:
- Identify and establish effective collaboration and funding support to advance the application of new technologies for delivery of improved paediatric formulations for TB treatment for susceptible and resistant TB
- Continue to support, with WHO and partners, the introduction of optimal paediatric formulations for treatment, and prevention of TB (3RH and 3HP).