BACKGROUND: The DISCOVER study is an ongoing randomized, double'blind study of pre-exposure prophylaxis (PrEP) using daily FTC/TAF (F/TAF; Descovy; DVY) or FTC/TDF (F/TDF; Truvada; TVD) in men or transgender women who have sex with men. Of the 5,335 randomized participants evaluated for HIV-1 infection, 24 (0.4%) became infected through a median of 120 Weeks on study. Here we present standard and ultrasensitive resistance testing from the DISCOVER participants who acquired HIV infection.
METHODS: Plasma samples from participants who became HIV-1 infected and had a viral load of > 400 copies/mL were tested with the Monogram GenoSure'¢ MG assay, using Sanger sequencing to analyze the protease (PR) and reverse transcriptase (RT) genes for any known resistance mutations (at '¥15-20% of the viral population). Identification of minor variants was evaluated using ultrasensitive resistance testing (at '¥1% of the viral population) that employed unique molecular identifiers for amplification of viral variants followed by next generation sequencing (UMI-NGS) to analyze RT codons 63-131 and 152-211 (University of Pittsburgh).
RESULTS: By standard sequencing, 4/20 HIV positive participants tested had M184V, all in the F/TDF group and all with suspected baseline infection; 2 of these 4 also had M184I present. Six participants had additional mutations conferring resistance to non-study drugs including NRTI, NNRTI, and PI, which were presumed to be transmitted.
By UMI-NGS, 23/24 HIV participants with HIV had samples available and 21/23 were successfully analyzed. The four participants with M184V each had M184I also detected; K65R was detected in 1 participant at very low levels. One participant on F/TAF had the M184V mutation present at 2%. Two out of 3 participants with samples that had viral loads < 400 copies/mL were successfully tested and neither had resistance to study drugs.
CONCLUSIONS: Using standard sequencing, M184V was detected in 4 participants, all in the F/TDF arm. Using ultrasensitive UMI-NGS testing, similar results were observed, with the addition of one participant with M184V in the F/TAF arm. Overall, drug resistance in the DISCOVER study was most commonly seen in participants with suspected baseline infections and in only 1 individual who became infected while on study.