The study is being billed as the first large-scale comparison of first-line treatments for HIV-positive children, and could have an impact on care in poor parts of the world, where most of them live.
Published in the Journal of the American Medical Association, the findings show initial treatment with efavirenz was more effective than nevirapine in suppressing the virus that causes AIDS in children aged three to 16.
The study involved more than 800 children, and was carried out by researchers from the Children's Hospital of Philadelphia, the Perelman School of Medicine at the University of Pennsylvania and the Botswana-Baylor Children's Clinical Center of Excellence.
The World Health Organization currently recommends both efavirenz and nevirapine in poor areas like sub-Saharan Africa, home to 90 percent of the world's more than three million HIV-positive children.
"Because nevirapine costs less than efavirenz and is more widely available in pediatric formulations, it is currently the more frequent choice," said lead author Elizabeth Lowenthal, of the Children's Hospital of Philadelphia.
"However, our study suggests that efavirenz produces better outcomes."
Senior author Robert Gross of Penn Medicine said that, given the evidence, it was "very reasonable to adjust pediatric treatment guidelines."
"However, as we move towards such changes, more work should be done to make efavirenz a more financially viable option for children on antiretroviral therapy in these resource-limited settings," he added.
Several previous studies have shown efavirenz to be more effective in adults, leading to it being recommended over nevirapine in a number of countries.
Nevirapine is produced by Boehringer Ingelheim, while efavirenz is marketed under the name Sustiva in the United States by Bristol-Myers Squibb.