JCI insight, September 2019
Ultrasensitive sequencing of HIV can reveal drug resistance mutations present at very low frequencies, but the clinical significance of those viral resistance mutations remains unknown.
Investigators used ultrasensitive single-genome sequencing (which detects very rare mutations on a single genome), on samples from the ACTG 5208/ OCTANE Trial (which assessed the response to NVP-containing ART among women who had prior exposure to single dose NVP 6–24 months before study entry and initiation of ART). They found that dual-class drug resistant mutations that were linked on the same genome were significantly associated with ART failure. Importantly, two single-class ART resistance mutations or dual-class mutations that were not linked on the same genome were not associated with subsequent treatment failure. Although nevirapine is no longer first-line, this finding of the impact of dual-class resistance on a single viral genome is likely to be true of other ART classes and highlights the powerful technologies (such as ultrasensitive sequencing) developed by investigators in the ACTG.