AIDS treatment for Children

Background

Children with HIV/AIDS are dying unnecessarily because of a lack of access to ARV treatment. The problems arise mainly from a lack of cheap feasible diagnostic tests for children under 18 months, lack of trained health personnel and the affordable child-friendly ARV drugs.

Simplified treatment guidelines coupled with a range of fixed-dose combinations of ARVs that require only one or two pills twice a day make it easier to treat HIV/AIDS in adults, but development of simplified drugs for children lags behind. Despite WHO simplified treatment guidelines that specify which drugs to use in children, countries have difficulty in getting simple and affordable combinations of the drugs. Two generic fixed-dose combinations should enter clinical trails this year, and there are frighteningly few second-line ARV drugs available for children in countries with large numbers of infected children.

Children orphaned by AIDS in Botswana (WHO/Eric Miller)

Therefore, WHO is committed to:

  • Ensuring children are included in national and international efforts to scale up access to treatment and reach "3 by 5" targets;
  • Greater coverage of ARV treatment, co-trimoxazole prophylaxis and comprehensive HIV care for HIV-exposed and HIV-infected infants;
  • Increasing access and coverage of PMTCT interventions to prevent infection in children;
  • Increased access to ART and HIV care for mothers, fathers and other care givers to propose or prevent orphanhood;

ARV formulations for children

Current global efforts to scale up access to treatment make a clear commitment to including access for infants and children. Existing programme efforts suggest even in successful ART programmes children are often not included. We have relatively little data or accurate forecasting or estimation of the needs for ART among HIV infected children. Of 12000 patients who accessed ART in MSF projects, only 700 (6%) were children (below 15 years) as of March 2004.

The "3 by 5" global target aims to include infants and children in at least 10-15% of all patients accessing ART. Many of the virologic and immunologic principles that underscore the use of ART are similar for all HIV-infected persons, but there are some unique considerations for HIV-infected infants and children. Specific factors related to pharmacokinetic and pharmacodynamics in paediatric populations influence ARV bioavailability. ARV selection and dosage calculations and paediatric specific factors also influence acceptability and adherence to treatment.

  • Not all ARVs in current WHO guidelines for children are currently made, or are available, in formulations suitable, palatable, acceptable or feasible for use in for paediatric populations
  • Lack of specific guidance on dosage adjustments for weight and age for currently recommended ARVs
  • Lack of pharmacokinetic and dynamic data on distribution, metabolism and efficacy & AUC for many ARV drugs in children
  • FDCs are not available in paediatric formulations
  • Current costs for paediatric formulations are well above the reduced prices achieved for adult ARV formulations
  • National and or international regulatory and prequalification procedures may discourage the production of specific paediatric ARV formulations

There are other problems that relate to the ability of national programmes to procure, supply and distribute paediatric formulations that influence the range and scope of paediatric ARV use in countries, and these include:

  • Need for supply systems to provide variable small volumes for paediatric use
  • Problems with supplies, shelf-lives, distribution and ongoing monitoring of drug quality up to the point of use; and
  • Complexity of dispensing to end-user and use by paediatric patients in community settings.

NOTE: The term “supply systems” referred to include the selection, procurement, storage, distribution and use of appropriate paediatric formulations, in this context.

Only a handful of the ARVs in the current WHO guidelines are available in formulations that are affordable, feasible or acceptable for use in infants and young children. Only 11 out of the 18 drugs used to treat adult HIV infection have indications, clear dosage or package inserts for use in children.

The global market for paediatric AIDS drug formulations is not attractive for originator or generic companies; in wealthy countries very few children are being born with HIV, and in developing countries where most of the infected children are, paediatric formulations are not considered a priority or lucrative market. Drug companies have made little progress to date in developing new or reformulating adult tablets and fixed-dose combinations to breakable or chewable tablets. Medicines for children are often beyond the reach of many families, and the cost of treating one child is often as much as six times more than an adult.

UNICEF/WHO Technical Consultation on Paediatric ARV Formulations

In November 2004, WHO and UNICEF held a technical consultation on: "Improving Access to Appropriate Paediatric ARV Formulations".

The aim of this meeting was to review the current status and development in the use of ARVs in HIV-infected infants and young children, with the specific intention of identifying immediate steps to increase access to appropriate antiretroviral formulations.

The meeting included experts from the Elizabeth Glazer Paediatric Foundation, the Clinton Foundation, Colombia University, researchers, pharmaceutical product development experts, the US Health and Human Services, Médecins Sans Frontières, national programme managers and clinical experts of HIV care in children from around the world.

Meeting agenda and presentations

Day 1 - Overview of paediatric formulations
 

9:00-9:15

- Background and objectives of meeting

Charlie Gilks, Siobhan Crowley, HIV/AIDS department of WHO
   
Plenary presentations

9:15-11.00

11.15-12.30


- Current experience and use of ARV treatment regimens for infants and young children in resource constrained settings

Doris Messia, MSF

- Experience With ARV Regimens for Infants/Children in Resource Constrained Settings
Catherine M Wilfert, MD, Elizabeth Glaser Pediatric AIDS Foundation (EGPAF)

- Currently experience of ARV care in relation to PMTCT, paediatric doses, experiences of use in countries Challenges to Pediatric Antiretroviral Treatment
Elaine Abrams, David Hoos MTCT-Plus

- Key Obstacles and Issues to provision of ART to Children in Resource-Poor Settings
Diana M Gibb Medical Research Council Clinical Trials Unit, UK

- Predicting the need for ARVs: Global estimates of burden of disease
Neff Walker, UNICEF

Group discussion: Current experiences of availability of paediatric ARV formulations: Key obstacles to scaling up access to paediatric HIV care

- Development pharmaceutics – formulations for paediatric ARVs
János Pogány, pharmacist, Ph.D., UNICEF/MSF/WHO

- Development of ARV FDC for Pediatric use
Alan Parr, Pharm.D., Ph.D. GlaxoSmithKline Research Triangle Park, NC

- Paediatric Antiretroviral PK
David Back, University of Liverpool, UK

- Ensuring secure and reliable supply and distribution systems in developing countries in the context of HIV/AIDS and PMTCT Access to Paediatric ARV Formulations: The plight of Children
Helene Möller M.Pharm, PhD Supply Division

- End-user factors influencing ARV formulations
Mark Cotton, Dept Paediatrics & Child Health, Tygerberg Children’s Hospital, Faculty of Health Sciences, Stellenbosch University South Africa

Group discussion: Key requirements of paediatric formulations to optimize therapeutic effect and end-user use in resource constrained settings


Presentation

 

Presentation

 

Presentation

 


Presentation


Presentation


Presentation


Presentation



Presentation


Presentation

Presentation

 

Presentation



Presentation

 

Plenary presentations

14:00-14:45


- A Demand Forecasting Tool for Pediatric Antiretroviral Medications

Stephen W.Nicholas by Clinton Foundation

- Preliminary deliberations towards estimating the burden of HIV disease in children, in the light of need for ART
Marie-Louise Newell, Kirsty Little, Madeleine Bunders


Presentation


Presentation

 
Group work
14:45-17:00


Group 1-
Definition of essential or best use ARV formulations required to deliver existing 'WHO first and second line regimens' in resource constrained settings for infants and children

GROUP 2 - Definition of characteristics of potential ideal formulations for paediatric ARVs, including FDCs and identification of additional formulations or ARVs required to be able to deliver paediatric ARV care

GROUP 3 - Evaluation of existing tools for demand forecasting, identifying the basic indicators that programmes need to be able to estimate and forecast Paediatric ARV needs, identifying the gaps

GROUP 4 - Mapping and prioritising the gaps and obstacles in knowledge, practice and clinical research, identifying immediate programmatic learnings priorities, recognizing longer term needs


Presentation


Presentation

 

Presentation

 

Presentation

 

Day 2 - Regulation, procurement supply and distribution factorsto formulations costs, access & availability

9:15 - 11:00


PLENARY PRESENTATIONS

- Development of Pediatric ARV Drugs – FDA Perspective
Linda L. Lewis, US Food and Drug Administration

- Prequalification and Paediatric ARV formulations
Marcus Stahl

- Improving access to appropriate paediatric ARV formulations - Key obstacles: MSF experience
Koen Frederix, MSF

- Demand, Supply and procurement issues including costs, and their impact upon access and availability of formulations

Helene Moller

- Dispensing and distribution to end user; including use of lay and alternative community based dispensing and effect upon choice and appropriateness of formulation

Mary Milcah Atieno Ojoo

Group discussion: Recognising how regulatory factors, supply, procurement and dispensing determine choice, use, effectiveness andcost of paediatric ARVs

 

Presentation


Presentation


Presentation


Presentation

 

Presentation

 


Presentation

Day 2 - Work group presentations


11.30-13.00

14:00-17:00


Group 1 and 2 - Key recommendations to R and D and generic pharmaceutical industry on the current and future ARV formulations required (including reformulation, label extension and new product development)

Group 1 - Key recommendations to national programmes on immediate selection of paediatric ARV to scale up access to paediatric care; best use of existing formulations, recommended dosing aids and tools to ensure best use

Group 2 - Key recommendations on strategies to facilitate product development, registration, licensing or and prequalification of new and modification ARV formulations

Group 3 - Recommendations for national programmes on minimum data requirements (indicators for programmes and populations) for demand forecasting and future programme planning clear list of existing gaps in existing tools, and next steps for optimizing the programming intelligence

Group 4- Urgent next steps to overcome key programme obstacles/gaps, unpacking the 3 - 5 key issues for programmatic leaning, clinical or operational research:, next steps, issues, methodology and partners

 

Presentation

 

Presentation


Presentation

 

Presentation

 

Presentation

Final conclusions

17:00-17:30

- Final report and recommendations

Note: The presentations from the meeting do not necessarily represent WHO positions and are put on the web site for information sharing purposes.


Share