title: Emergent HIV-1 Drug Resistance Mutations Were Not Present at Low-Frequency at Baseline in Non-Nucleoside Reverse Transcriptase Inhibitor-Treated Subjects in the STaR Study.
abstract: At Week 96 of the Single-Tablet Regimen (STaR) study, more treatment-naïve subjects that received rilpivirine/emtricitabine/tenofovir DF (RPV/FTC/TDF) developed resistance mutations compared to those treated with efavirenz (EFV)/FTC/TDF by population sequencing. Furthermore, more RPV/FTC/TDF-treated subjects with baseline HIV-1 RNA >100,000 copies/mL developed resistance compared to subjects with baseline HIV-1 RNA ≤100,000 copies/mL. Here, deep sequencing was utilized to assess the presence of pre-existing low-frequency variants in subjects with and without resistance development in the STaR study. Deep sequencing (Illumina MiSeq) was performed on baseline and virologic failure samples for all subjects analyzed for resistance by population sequencing during the clinical study (n = 33), as well as baseline samples from control subjects with virologic response (n = 118). Primary NRTI or NNRTI drug resistance mutations present at low frequency (≥2% to 20%) were detected in 6.6% of baseline samples by deep sequencing, all of which occurred in control subjects. Deep sequencing results were generally consistent with population sequencing but detected additional primary NNRTI and NRTI resistance mutations at virologic failure in seven samples. HIV-1 drug resistance mutations emerging while on RPV/FTC/TDF or EFV/FTC/TDF treatment were not present at low frequency at baseline in the STaR study.
authors.affiliation: Gilead Sciences, 333 Lakeside Drive, Foster City, CA 94404, USA. danielle.porter@gilead.com.
authors.forename: Danielle P
authors.initials: DP
authors.lastname: Porter
authors.affiliation: Seq-IT GmbH &amp; Co. KG, Pfaffplatz 10, 67655 Kaiserslautern, Germany. m.daeumer@immungenetik-kl.de.
authors.forename: Martin
authors.initials: M
authors.lastname: Daeumer
authors.affiliation: Seq-IT GmbH &amp; Co. KG, Pfaffplatz 10, 67655 Kaiserslautern, Germany. a.thielen@immungenetik-kl.de.
authors.forename: Alexander
authors.initials: A
authors.lastname: Thielen
authors.affiliation: Gilead Sciences, 333 Lakeside Drive, Foster City, CA 94404, USA. silvia.chang@gilead.com.
authors.forename: Silvia
authors.initials: S
authors.lastname: Chang
authors.affiliation: Gilead Sciences, 333 Lakeside Drive, Foster City, CA 94404, USA. ross.martin@gilead.com.
authors.forename: Ross
authors.initials: R
authors.lastname: Martin
authors.affiliation: Gilead Sciences, 333 Lakeside Drive, Foster City, CA 94404, USA. cal.cohen@gilead.com.
authors.forename: Cal
authors.initials: C
authors.lastname: Cohen
authors.affiliation: Gilead Sciences, 333 Lakeside Drive, Foster City, CA 94404, USA. michael.miller@gilead.com.
authors.forename: Michael D
authors.initials: MD
authors.lastname: Miller
authors.affiliation: Gilead Sciences, 333 Lakeside Drive, Foster City, CA 94404, USA. kirsten.white@gilead.com.
authors.forename: Kirsten L
authors.initials: KL
authors.lastname: White
mesh_terms: D000328:Adult; D019380:Anti-HIV Agents / Q000494:pharmacology / Q000627:therapeutic use*; D023241:Antiretroviral Therapy, Highly Active / Q000379:methods*; D052687:Deltapapillomavirus; D024882:Drug Resistance, Viral; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology; D015497:HIV-1 / Q000187:drug effects* / Q000302:isolation & purification; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D012367:RNA, Viral / Q000235:genetics; D018894:Reverse Transcriptase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D017211:Treatment Failure; D055815:Young Adult
chemical_list: D019380:Anti-HIV Agents; D012367:RNA, Viral; D018894:Reverse Transcriptase Inhibitors
keywords: efavirenz; minority variants; resistance; rilpivirine; virologic failure