Pre-treatment integrase strand transfer inhibitor resistance in north carolina from 2010-2016.

OBJECTIVE: We sought to define the prevalence of pre-treatment INSTI resistance and assess the transmission networks of those with pre-treatment INSTI resistance.

DESIGN: A retrospective cohort study of HIV-positive patients with genotypic resistance testing sent to a single referral laboratory in North Carolina between 2010 and 2016.

METHODS: We linked genotype and public health data for in-care HIV-positive individuals to determine the prevalence of INSTI resistance among treatment-naïve (defined as those with a first genotype ≤3 months after diagnosis) and treatment-experienced (defined as those with a first genotype >3 months after diagnosis) patients. We performed molecular and phylogenetic analyses to assess whether pre-treatment INSTI resistance mutations represented clustered HIV transmission.

RESULTS: Of 8825 individuals who contributed sequences for protease (PR), reverse transcriptase (RT), or INSTI genotypic resistance testing during the study period, 2784 (31%) contributed ≥1 sequence for INSTI resistance testing. Of these, 840 were treatment-naïve individuals and 20 (2.4%, 95% confidence interval [CI]: 1.5, 3.6%) had INSTI mutations; only two (0.2%, 95%CI: 0.02, 0.9%) had major mutations. Of 1944 treatment-experienced individuals, 9.6% (95%CI: 8.3, 11.0%) had any INSTI mutation and 7.0% (95%CI: 5.9, 8.3%) had major mutations; the prevalence of INSTI mutations among treatment-experienced patients decreased over time (P < 0.001). Twelve of 20 individuals with pre-treatment INSTI mutations were part of 10 molecular transmission clusters; only one cluster shared identical minor mutations.

CONCLUSION: The prevalence of major pre-treatment INSTI resistance is very low. Pre-treatment INSTI mutations do not appear to represent clustered HIV transmission.