HIV-1 drug resistance and second-line treatment in children randomized to switch at low versus higher RNA thresholds. Journal of Acquired Immune Deficiency Syndrome
Harrison et al. explored resistance profiles after first-line antiretroviral therapy (ART) by randomized switch criteria based on RNA threshold (>1’000 copies/ml versus >30’000 copies/ml), and second-line treatment response in children. They found that children starting NNRTIs accumulated more NRTI mutations than those starting protease inhibitors (PIs). Children switching later on NNRTIs accumulated more NRTI mutations, whereas on PIs, NRTI mutations did not accumulate over the time. Children on first-line NNRTI-based ART who were randomized to switch at a higher virologic threshold developed the most resistance, yet resuppressed on second-line.
Overall, these data support WHO 2013 pediatric guidelines recommending abacavir + lamivudine as the first-line NRTI backbone with an NNRTI and provide reassurance that response to second-line with a boosted PI and zidovudine + lamivudine is expected to be good.