Emergence of Resistance to Integrase Strand Transfer Inhibitors during Dolutegravir Containing Triple-Therapy in a Treatment-Experienced Patient with Pre-Existing M184V/I Mutation

Abstract

With the current widespread use of dolutegravir in low-income countries, the understanding of the impact of nucleoside reverse transcriptase inhibitor (NRTI-) associated mutations on the efficacy of dolutegravir-containing antiretroviral therapy (ART) is of utmost importance. We describe a rare case of a patient with pre-existing M184V/I mutation and virological failure on a dolutegravir/lamivudine/abacavir regimen with the emergence of integrase strand transfer inhibitor resistance mutations. Additional risk factors, which may have triggered the virological failure, included suboptimal adherence and low nadir CD4+ cell count. This case illustrates that dolutegravir-containing triple-therapy should be prescribed with caution to patients with pre-existing M184V/I mutation and poor efficacy of the reverse transcriptase inhibitor backbone. In addition, this case highlights the need for viral load monitoring in patients on dolutegravir-containing regimens in settings with a high prevalence of the M184V/I mutation such as in low-income countries.

Keywords: HIV-1; M184V/I mutation; antiretroviral therapy; dolutegravir; drug resistance; integrase strand transfer inhibitor; virological failure.

Figure 1

Virological evolution and emergence of resistance-associated mutations (arrows pointing downwards) of our patient since initiation of antiretroviral treatment. Abbreviations: ART: antiretroviral treatment, 3TC: lamivudine, D4T: stavudine, NFV: nelfinavir, SSITT: Swiss Spanish Intermittent Treatment Trial, FAPV/r: fosamprenavir/ritonavir, TDF: tenofovir disoproxil-fumarate, FTC: emtricitabine, (*) add-on raltegravir for one month, DRV/r: darunavir/ritonavir, ETV: etravirine, TAF: tenofovir alafenamide, LOQ: level of quantification. The persisting M184V/I mutation is highlighted in bold.