Research in HIV-1 paediatric infection is limited in breadth and scope compared to that pertaining to adults. Research on the antiretroviral treatment of children has, although often years later, identified the same factors in children as critical for successful treatment as have been identified in adults.
These factors, viral resistance, potency of the drug regimen, therapeutic drug monitoring, and adherence to the regimen, are mentioned in the i-Base introduction. As they also mention, incorporating 'recent findings' and 'new insights' into the care of children with HIV has often lagged behind that of adults. And although, not explicitly stated, they imply, that all involved should aspire to excellent state-of-the-art care for HIV infected children.
Paediatric HIV providers have the difficult task of evaluating research conducted in adults and deciding which aspects warrant translation, prior to the repetition of similar studies in children.
Rapid implementation of certain findings to paediatric care seems warranted when there is a significant potential benefit to children, or when harm might result by ignoring the findings. Because children are different from adults, careful consideration of studies done in adults is necessary to determine their 'paediatric relevance'.
Conscientious experts need to lead the paediatric community in this endeavor so that we provide the best care possible to all infected children.
Lisa Frenkel and Stefano Vella
Co-chairs
As we go to print, the most comprehensive published guidelines for treating children with HIV, The US Guidelines for the Use of Antiretroviral Agents in Paediatric HIV Infection, are already over a year old, and unreflective of the clinical care provided by many of the contributors to this report. Whilst guidelines in any fast-changing medical field such as HIV will always lag behind the latest research, it is unfortunate that a similar monthly review and support network to that for adult care is not available.
In the UK advocacy for adult care (for example - access to triple therapy, to viral load and resistance tests, TDM, the importance of aiming for undetectable viral suppression below 50 copies/ml, early switching of failing regimens etc) was something of an uphill struggle. One of the current concerns in adult care is that treatment success, whether for first-line or subsequent therapies, is dependent on several key factors, none of which can be ignored. Potency, resistance, drug levels and adherence are all essential parts of the equation, and that this is similarly being realised in paediatrics, and is reflected in the presentations from this meeting, is very encouraging.
Children have been frequently treated with combinations that are insufficiently potent to suppress the virus, quickly leading to the development of resistance. At one time it was thought unrealistic to aim for maximal suppression due to childrens' higher viral load but, again optimistically, this view has also changed. We highlight strategies that start treatment with potent 4-drug regimens from both UK and US clinicians that are aiming for and achieving higher success rates. And although resistance tests for adults have now been integrated into standard of care, and despite identical reasons for accessing them, this is not the case yet for children.
As we all hope, and Di Gibb explained, 'these children are going to live for at least twenty or thirty years' but 'they have run out of everything in two and we know from data that you are half as likely to respond to your second regimen as your first.'
Long-term use of antiretroviral therapy is raising new concerns of associated toxicity. The meeting included an important presentation on lipodystrophy - and that likelihood that it is currently being under-diagnosed - together with a discussion on Strategic Treatment Interruptions as as strategy to manage long-term treatment.
In the UK we have one of the world's foremost pharmacology departments at Liverpool University, but the support services it offers to all UK clinics for therapeutic monitoring of antiretroviral drugs are still under-accessed. For paediatric care, where optimal dosing is notoriously difficult to determine, TDM for any PI or NNRTI should also be standard of care, as is the case in both France and Holland. Most importantly, subsidised programmes provided by Roche and Merck will ensure that all costs for this service are covered for all children using nelfinavir, saquinavir or indinavir including combinations. The appropriate form and contact details are included in Appendix VI for clinicians that have yet to access this service.
The central role of adherence in the success of any treatment is stressed over and over again. We look at the importance of support within the community and at practical ways to make medicines easier to take, like using g-tubes and teaching pill swallowing.
But even at 44-pages, this report left out a lot of material from the discussions and presentations. We believe there is an important role for, and would love to see, a regular international meeting on the subject of paediatrics - would anyone like to take up the challenge?
Finally we were, as always, completely blown away by the generosity of our speakers. Some who were prepared to fly half way round the world (or in the case of UK paediatricians, risk the wrath of their own families during a half-term holiday), to speak at a meeting, organised by activists, that in a few cases they had never even met.
You have our warmest thanks.
Polly Clayden and Simon Collins, HIV i-Base
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