Carole Leach-Lemens, aidsmap.com, Published: 26 April 2011:
One in eight children and adolescents receiving HIV treatment at major HIV clinics in Europe experienced failure of three classes of antiretroviral drugs after five years of treatment, highlighting the need for formulations of new antiretroviral drugs to be developed that are suitable for children, European researchers report in The Lancet.
Triple-class failure implies that children has experienced the failure of at least two antiretroviral regimens, one containing a non-nucleoside reverse transcriptase inhibitor combined with a nucleoside analogue, and one containing a protease inhibitor combined with a nucleoside analogue. It also implies a degree of cross-resistance to other drugs in the same class.
Children were twice as likely as adults with HIV in Europe to experience failure of their first antiretroviral regimen.
The PLATO II investigators for the Collaboration of Observational HIV Epidemiological Research in Europe (COHERE) reported a retrospective cohort study of 1007 children, among whom over one-third (33%) had started a third drug class after a median of 4.2 years (of which 105 (44% or 10% overall) were on a failing regimen).
About 25% of those who developed triple-class virological failure had never achieved viral suppression (a viral load measurement under 500 copies/mL).
The longer the children were on ART the greater the risk of triple-class virological failure: after five years the risk was 12% (95% CI: 9.4-14.6).
Approximately 2 million children are living with HIV, the majority infected through perinatal transmission. An estimated 700 children die every day because of AIDS-related causes. Without treatment an estimated 50% will die before they reach the age of two.
Antiretroviral therapy has dramatically improved the prognosis for HIV-infected children. Children have responded well to protease inhibitors (PIs) and non-nucleoside reverse transcriptase inhibitors (NNRTIs). Guidelines now recommend starting treatment as soon as possible after HIV diagnosis.
Results from adults treated, in both resource-poor and resource-rich settings, with all three classes of antiretrovirals (PIs, NNRTIs and nucleoside reverse transcriptase inhibitors (NRTIs) suggest that long-term viral suppression is possible and virological failure happens slowly. It is unclear whether the same is true for children who will need to maintain viral suppression the longest.
The major challenge in treating children is to minimise virological failure and the development of drug resistance so that children will continue to have treatment options throughout adolescence and adulthood.