News Release

Study of European HIV-positive children shows that 1 in 8 experience triple-class virological failure by 5 years after starting antiretroviral treatment

Peer-Reviewed Publication

The Lancet_DELETED

A study of European HIV-positive children, published Online First by The Lancet, shows that 12% of children (around 1 in 8) develop triple-class virological failure by 5 years after starting their antiretroviral drug treatment programme. This is higher than the failure rate in adults, and underlines the difficulties in maintaining viral load suppression in those who start treatment very early in life. The study is by Dr Ali Judd, UK Medical Research Council Clinical Trials Unit, London, UK, and colleagues, and was funded by the UK Medical Research Council.

In adults with HIV treated with antiretroviral drug regimens from within the three original drug classes (nucleoside or nucleotide reverse transcriptase inhibitors [NRTIs], non-NRTIs [NNRTIs], and protease inhibitors), virological failure occurs slowly, suggesting that long-term viral load suppression can be achieved in most people, even in areas where access is restricted to drugs from these classes. Prior to this new work, it was unclear whether this was the case for children, the group who will need to maintain viral suppression for longest.

A total of 1007 European children were identified in the 14 Collaboration of Observational HIV Epidemiological Research Europe cohorts. The UK and Ireland, Spanish, Dutch, and French cohorts contributed more than 90% of children, with a smaller proportion from Denmark, Italy, Belgium, and the European Collaborative Study. The rate of triple-class virological failure was studied in children infected with HIV perinatally (from their mother at or before birth) who were aged less than 16 years, starting antiretroviral therapy (ART) with three or more drugs, between 1998 and 2008.

A total of 237 (24%) were exposed to triple-class therapy and by five years after initiation, the rate of triple-class failure across the whole cohort was 12%. Further analysis showed that older age at ART initiation was associated with increased risk of failure. Of 686 children starting ART with NRTIs and either a NNRTI or ritonavir-boosted protease inhibitor the rate of failure was more than twice as high than in adults with heterosexually transmitted HIV.

The authors say: "The rate of virological failure of the three original drug classes seen in this study shows the challenge of maintaining lifelong viral suppression in children who start ART much earlier in life than do adults. Further detailed analysis is needed to compare rates of switching to second-line ART and viral suppression on second-line ART between adults and children, and to compare the development of resistance."

They conclude: "There is continued need for strategies to promote optimum drug adherence in children, caregivers, and young people to minimise the likelihood of triple-class virological failure, and for development of suitable new drugs and formulations to optimise the treatment of children with treatment failure. Fixed drug combinations and simplification of strategies could be important ways to maintain treatment options while children move through adolescence and reach adulthood."

In a linked Comment, Dr Alexandra L Calmy and Dr Nathan Ford Campaign for Access to Essential Medicines, Médecins Sans Frontières, Geneva, Switzerland, point out that without antiretroviral treatment over half will die before the age of 2 years, and that some 90% of children with HIV live in developing countries.

They discuss how difficulty of storing syrup-style formulations, plus the unpalatable nature of some antiretroviral drugs, make correct adherence complicated. They say: "Currently only four quality-assured triple-drug fixed-dose combinations are available in solid and dispersible forms from manufacturers of generic drugs, and less desirable dose formulations continue to dominate this small and fragmented market."

They conclude that the inclusion of paediatric HIV/AIDS in the Drugs for Neglected Diseases initiative shows conclusively that this area is neglected on global agendas.


Dr Ali Judd and other authors, UK Medical Research Council Clinical Trials Unit, London, UK. Via Medical Research Council Press Office T) +44 (0) 207 395 2345 E)

Dr Alexandra L Calmy and Dr Nathan Ford Campaign for Access to Essential Medicines, Médecins Sans Frontières, Geneva, Switzerland. T) +41 79 412 8212 E)

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