Treatment Failure in Children with HIV

Maintaining durable virologic suppression is critical for all HIV-infected patients, but particularly so for children, who require lifelong antiretroviral therapy (ART). A recent report from the PLATO II project describes the rate and predictors of triple-class virologic failure in a large pediatric cohort in Europe.

More than 1000 children were followed for a median of 4.2 years from the time of ART initiation in 1998 or later. Risk for triple-class failure was estimated to be 12% by year 5 of ART and 20% by year 8. When the cohort was restricted to the 686 children whose initial regimens were similar to those recommended for adults (2 or 3 nucleoside reverse transcriptase inhibitors [NRTIs] plus a nonnucleoside reverse transcriptase inhibitor [NNRTI] or a ritonavir-boosted protease inhibitor [PI]), the 5-year risk for triple-class failure was estimated to be 8%, as compared to 4% for adults in the PLATO II project (adjusted hazard ratio, 2.2).

One third of children with triple-class failure never achieved viral loads <500 copies/mL. These children were significantly younger at ART initiation than those who achieved virologic suppression before failure (median age, 1.8 vs. 6.1 years). Among the variables analyzed as potential predictors of failure, only older age at ART initiation (10–15 years) emerged as significant.

Resistance test results were examined for 40 children with triple-class failure who had received ritonavir-boosted PIs. Although NRTI and NNRTI mutations were present in the majority, none had any protease mutations, suggesting that adherence interventions may be particularly critical for such children.