Primary integrase inhibitor resistance transmission is rare and has been reported in the context of multidrug resistance, which is consistent with the initial use of integrase inhibitors in the ART-experienced setting. However, over the years, integrase inhibitors have moved to first-line therapy due to the efficacy, tolerability, and the availability of multiple single tablet integrase inhibitor based regimens. This report describes two cases of antiretroviral naïve individuals who were infected with integrase inhibitor resistant viruses without other drug class resistance, and includes the first reported case of primary elvitegravir only resistance transmission.
Two patient cases with primary integrase inhibitor resistance without other class resistance were identified in a New York City private practice. Histories were obtained, and resistance mutations were analyzed through genotyping and phenotyping.
Case#1: Patient KG was last HIV negative on 11/11. KG tested positive for HIV on 4/9/13. 4/16/13 Vircotype: pansensitivity, Trofile: “non-reportable”, Phenosense Integrase test: 7.6x resistance to elvitegravir and a 52x resistance to raltegravir. 5/7/13 Quest Integrase Genotype: Y143R, L74M, and R263R/K mutations, Quest tropism: R5 virus. 5/8/13 GenosurePrime: pansensitivity in all drug classes except for the integrase class (Y143R, T97T/A, and L74I/M).
Case #2: Patient TM was diagnosed with HIV on 5/09. 1/13 established care here. Baseline Vircotype: pansensitivity, Trofile: R5 virus, Phenosense Integrase: pansensitivity. Remained ART-naïve as his T cells were 600-900 and VL 10-20K. Due to the START trial, on 9/17/15 the patient contemplated treatment initiation; Genosure Archive: Major S147 S/G non-polymorphic elvitegravir only integrase inhibitor mutation without evidence of other mutations to any other drugs.
These are the first two documented cases of integrase inhibitor primary drug resistance transmission in the absence of other drug class resistance in ART-naïve patients, including the first case of elvitegravir only primary major drug resistance acquisition. With the advent of integrase inhibitors as first line therapies, considerations for baseline integrase inhibitor resistance testing may be considered in high-risk demographic settings.
R. Hsu, None