by Jeffrey T. Kirchner, DO, AAHIVS, AAHIVM Chief Medical Officer
May 19, 2020
Henegar CE et al. Trends in HIV Drug Resistance in the United States (2012-2018). CROI, 2020 / Boston, MA. # 521 (Session P-103).
Both acquired and transmitted HIV-1 drug resistance impacts efficacy of antiretroviral therapy (ART) in persons living with HIV. This study utilized data from the Monogram Biosciences database to assess yearly trends in viral resistance in the U.S. There were 84,611 samples submitted for routine genotype testing from 2012 to 2018 of which 27,911 (33%) showed reduced susceptibility to at least one of the four classes of antiretroviral drugs. The four classes include protease inhibitors (PI), nucleoside reverse transcriptase inhibitors (NRTI), non-nucleoside reverse transcriptase inhibitors (NNRTI), and integrase strand transfer inhibitors (INSTIs). From 2012 to 2016, resistance to NNRTIs was most common and remained fairly consistent from 76% to 73%. However, resistance to NRTIs declined from 55% to 41% and for PIs from 15% to 8%. The proportion of samples with reduced susceptibility to at least one INSTI decreased from 20% to 14% with no change after 2015. Regarding multiclass resistance (≥2 ARV classes) this also declined between 2012 and 2018. The proportion of resistant samples with 2-class resistance decreased from 34% to 22%. For 3-class resistance it declined from 11% to 6% and for 4-class resistance from 3% to 1%. Among samples with multiclass resistance, 79% remained susceptible to at least 1 ARV in the NNRTI class, 93% to ≥1 NRTI, 98% to ≥1 PI, and 94% to ≥1 INSTI. Not surprising, the proportion of samples with multi-drug resistance increased with age, being highest at 42% in persons over the age of 60 years, likely reflecting a longer time on ART.
The declining trends in ARV resistance during this time period is probably due to several factors. These include improved efficacy of newer agents, higher genetic barriers to resistance, and the growing use of single-tablet regimens which have improved adherence to therapy. The increase in Non-NRTI resistance likely represents first-line treatment failure to nevirapine, efavirenz, and rilpivirine – agents with a low genetic barrier to resistance and whose use has declined in favor of INSTIs. This study did not distinguish between acquired and transmitted resistance – the latter which has been addressed by other studies.