Journal Club 

Transmitted HIV Drug Resistance in the United States

By Lauren Richey, MD, MPH, FIDSA

Transmitted drug resistance is important because it can impact treatment outcomes for people with HIV and prevention outcomes for people on preexposure prophylaxis (PrEP). Drug resistance testing for most antiretroviral (ART) drug classes, other than integrase inhibitors, is recommended for people with newly diagnosed HIV and is reported to the National HIV Surveillance System. Patients who had genotype tests within 3 months of HIV diagnosis from 2014 to 2018 were included in a recent analysis, published in Clinical Infectious Diseases, from the 28 states that account for the majority of new infections (70%). In these included states, > 20% of the newly diagnosed had genotypes available.

More than 50,000 people were included in the analysis. Twenty percent had an integrase sequence available. Most patients were male (83%), African American (38.4%), from the South census region (47.1%), and had male-to-male sexual transmission as their risk factor (69.2%). Overall, 18.9% had a transmitted drug resistance mutation (TDRM). Non-nucleoside reverse transcriptase inhibitor mutations were found in 12%, nucleoside reverse transcriptase inhibitor mutations in 6.9%, and protease inhibitor mutations in 4.2%. Only ~10,300 (20%) had an integrase sequence available, and 0.8% had an integrase TDRM. The most common integrase inhibitor mutation was E138K (0.2%). The most common mutation overall was K103N at 8.6%. M184V prevalence was 0.9%, and K65R prevalence was 0.1%. Resistance to two drug classes was relatively uncommon (2.3%).

TDRM prevalence increased from 14.6% to 18.9% from 2006 to 2014. However, overall TDRM prevalence for current first-line ART regimens remained low. The low rates of transmitted M184V and K65R are reassuring as they are the mutations associated with the medications in PrEP. However, the estimates for these mutations and others in the study may be underestimates since many mutations decay within weeks or months of infection, and most newly diagnosed patients are not newly infected. The most common integrase TDRM, E138K, was still relatively uncommon, and impacts susceptibilities to raltegravir and elvitegravir, which are less commonly used.

(McClung et al. Clin Infect Dis. Published online: June 27, 2021.)