HIV treatment guidelines state that genotypic resistance testing should be obtained at diagnosis. Integrase strand transfer inhibitors (INSTIs) have emerged as initial regimens for persons newly diagnosed with HIV because of their clinical effectiveness and tolerability. However, with widespread use of INSTIs, the concerns of transmitted integrase (IN) drug resistance and risk of virologic failure are rising among clinicians. The aims of this analysis were to explore 1) the frequency of IN testing and risk factors associated with IN testing, 2) the rate of transmitted IN drug resistance, and 3) common clinically significant INSTI-resistance mutations among persons with newly diagnosed HIV in New York State (NYS).
Persons age 13 and older diagnosed between 2013-2017 and reported to the NYS HIV registry were included in the study. The first IN nucleotide sequence for an individual was identified and flagged as an ‘initial’ test if ordered within 3 months of the HIV diagnosis date. Persons with 1) incomplete diagnosis or test dates or 2) invalid sequences were excluded. Multivariable analysis was used to test the association between IN initial testing and sociodemographic factors. Sequences were analyzed using the NYS in-house Resistance Analysis System and compared with major INSTI resistance mutations published on Stanford HIVdb Program website.
Overall, 15,345 persons were included; 59.2% had any resistance testing within 3 months of diagnosis. 20.9% (3,209) had initial IN testing; 2.5% had only IN testing. Initial IN testing increased significantly from 5.6% in 2013 to 32.4% in 2017. The likelihood of having initial IN test was lower in minorities than whites (RR:0.87, 95%CI:0.79-0.96), and higher among males with a history of male-to-male sexual contact than heterosexuals (RR:1.31, 95%CI:1.09-1.58). Resistance to ≥1 IN drug was seen in 0.7% (24) of 3,209 persons with initial tests. The most common clinically significant INST-resistance mutations were: E138A/K, N155H/S, Q148H/K/R, E92G/Q, T66A/I, G140C/S, Y143C/R.
Clinician ordering of initial resistance testing lags current guidelines. These data indicate that initial IN testing has increased among persons newly diagnosed with HIV. While IN drug resistance remains low, clinically significant major mutations observed suggests that transmitted IN resistance is emerging; it is importance for clinicians to order IN test at time of HIV diagnosis for treatment decision.