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

• Published in: Viruses Vol. 7; no. 12; pp. 6360 - 6370
• Main Authors: Porter, Danielle, Daeumer, Martin, Thielen, Alexander, Chang, Silvia, Martin, Ross, Cohen, Cal, Miller, Michael, White, Kirsten
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI 07.12.2015; MDPI AG
• Subjects: Adult; Anti-HIV Agents - pharmacology; Anti-HIV Agents - therapeutic use; Antiretroviral Therapy, Highly Active - methods; Deltapapillomavirus; Drug Resistance, Viral; efavirenz; Female; High-Throughput Nucleotide Sequencing; HIV Infections - drug therapy; HIV Infections - virology; HIV-1 - drug effects; HIV-1 - isolation & purification; Humans; Male; Middle Aged; minority variants; Mutation; resistance; Reverse Transcriptase Inhibitors - pharmacology; Reverse Transcriptase Inhibitors - therapeutic use; rilpivirine; RNA, Viral - genetics; Treatment Failure; virologic failure; Young Adult; virologic failure; minority variants; efavirenz; resistance; rilpivirine
• ISSN: 1999-4915; 1999-4915
• DOI: 10.3390/v7122943

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.