A Landmark ACTG Study Evaluating Second-Line ART Failure in Low- and Middle-Income Countries

The Lancet HIV, September 2019

Prolonging the success of ART regimens in light of earlier starts and therapy over a lifetime requires innovative monitoring and treatment strategies. The Management Using the Latest Technologies in Resource-Limited Settings to Optimize Combination Therapy After Viral Failure (MULTI-OCTAVE) A5288 study was an open-label phase IV strategy study conducted in 19 sites in 10 lower- and middle-income countries (in Africa, Asia, South America, and the Caribbean) for patients failing second-line ART. This study used newer antiretroviral therapies (ART) and contemporary management approaches, including population-based sequencing to select appropriate antiretrovirals, to evaluate virologic outcomes and emergence of resistance. A5288 is an unprecedented cohort of second-line ART failure in lower- and middle-income countries, incorporating rigorous metrics of adherence measurement (via hair levels) and resistance testing into its design. In an accompanying editorial, A5288 was hailed as “a major step forward in clinical research methods serving a rarely studied population.”