The ADVANCE study: a groundbreaking trial to evaluate a candidate universal antiretroviral regimen

Current WHO-recommended first-line therapy in low-income and middle-income countries has been very successful in saving millions of lives but still has toxicity concerns and a low barrier to resistance.

Two candidate antiretrovirals may substantially transform first-line therapy in low-income and middle-income countries, yielding a safer, more robust and cheaper regimen. Tenofovir alafenamide carries toxicity and cost benefits over tenofovir disoproxil fumarate. Dolutegravir could replace efavirenz, with substantial toxicity, resistance and cost benefits. However, these drugs are currently not manufactured together in developed countries, for commercial reasons.

We describe a large randomized controlled study testing a combination of these candidate antiretrovirals against the current first-line recommendation that commenced recruitment in early 2017. We justify the study design and discuss how we will deal with complex issues such as tuberculosis and pregnancy.