According to a new major study one in eight children born with HIV becomes resistant to the three main classes of drugs used to suppress the virus within five years of starting treatment. This is the first major study that looks at drug resistance in 1,000 European children born with HIV. It raises questions about the suitability of anti-retroviral drugs for the young.
Experts say that the drugs fail because the virus becomes resistant to them. This can happen if people take them erratically or stop taking them. Resistance sets in with adults, but more slowly.
Nathan Ford and Alexandra Calmy say part of the problem is that the drugs available are not tested on children or turned into formulations that are easy for children to take. These doctors work for Médecins sans Frontières, which treats some of the 2 million children living with HIV, who were infected during childbirth – most of them in the developing world. Half of the children born with HIV die before their second birthday, they explain. They write that even in the US and Europe, drugs for children with HIV is limited. “Of the 22 antiretroviral drugs currently approved by the US food and drug administration, five are not approved for use in children and six are not available in pediatric formulations…Additionally, treatment has to be constantly adjusted for bodyweight, and most paediatric anti-retrovirals are formulated as syrups (often in large volumes) which are difficult to administer and store." Some of the drugs, they add, "are extremely unpalatable,” they write in a commentary published with the study in the Lancet medical journal.
Since children with HIV do not survive beyond their second birthday they say to give more children a chance of staying alive, fixed-dose combinations of a three-drug cocktail are needed, in tablet form. They call on “drug developers, clinical trial investigators and drug regulators” to prioritize the production of better HIV drugs for children.
This study was conducted in UK, Ireland, Spain, the Netherlands and France, with smaller numbers also from Denmark, Italy and Belgium. The children were all younger than 16 and had started treatment with three or more drugs between 1998 and 2008.
The results showed that the failure rate is seen in three main classes of drugs – known as nucleoside or nucleotide reverse transcriptase inhibitors (NRTIs), non-NRTIs (NNRTIs), and protease inhibitors. The failure rate was 12% within five years of starting. There were problems even with young children, where the parent or carer would be responsible for giving the medicine, but the failure rate was higher in older children. The children were followed for a median of 4.2 years. The researchers examined their viral loads and any occurrences of virologic failure, defined as a viral load greater than 500 copies per milliliter of blood after four months of treatment. At the end of the study period, 24 percent of the children were taking anti-retrovirals from all three drug classes (NRTIs, NNRTIs, and protease inhibitors). Of these, 44 percent (10 percent of the total study population) experienced virologic failure while taking a triple-class regimen.
Nearly 28 percent of the children who experienced triple-class virologic failure never attained a viral load of less than 500 copies per milliliter during the study period. These children were more likely to have started treatment younger (a median age of 1.8 years) than children who had achieved low viral loads at least once before experiencing triple-class virologic failure (median age of 6.1 years). They were also more likely to have started treatment with all three classes of anti-retrovirals earlier (median of 2.1 years after treatment initiation versus 3.3 years, respectively).
Based on their results, they recommended further research into strategies to improve medication dosing and adherence in children and teens. “Drug adherence is a challenge for children and young people with any chronic disease. For those with HIV infection, there are additional factors, including coming to terms with disclosure of their HIV status, secrecy and guilt among adult family members and dealing with HIV alongside their own sexual development. Fear of stigma increases their isolation and tendency towards denial, all of which might adversely affect drug adherence,” the authors write.
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