Virologic suppression in patients with a documented M184V/I mutation based on the number of active agents in the antiretroviral regimen

Abstract

Objectives: The optimal antiretroviral therapy for patients with the M184V/I mutation is not known. The primary objective of this study was to determine the efficacy of various antiretroviral therapies in patients with HIV and the M184V/I mutation based on the number of active antiretroviral agents. Methods: A retrospective chart review was conducted of 100 treatment-experienced patients harboring the M184V/I mutation seen at an urban HIV clinic. Efficacy was classified as percentage of patients with viral suppression defined as HIV RNA viral load <200 copies/mL at last measurement on current antiretroviral therapy, stratified by the number of active antiretroviral agents. Results: The primary outcome of viral suppression occurred in 70.6% (12/17) of patients on <2 active agents, 77.2% (44/57) on 2–2.5 active agents, and 69.2% (18/26) on 3 active agents. No significant difference was found between viral suppression and patients on <2 and 2–2.5 antiretroviral agents (odds ratio = 0.71, 95% confidence interval = (0.21, 2.39), p = 0.8) or between patients on 3 and 2–2.5 active agents (odds ratio = 0.66, 95% confidence interval = (0.23, 1.88), p = 0.7). The most commonly prescribed regimen consisted of a boosted protease inhibitor with an integrase strand transfer inhibitor and two nucleoside reverse transcriptase inhibitors, one of which being lamivudine or emtricitabine. Conclusion: Similar rates of viral suppression were observed in patients regardless of the number of active antiretroviral agents prescribed. Regimens containing less than 3 active agents may maintain virologic suppression in patients with the M184V/I mutation. Further studies are needed to determine optimal antiretroviral therapy for patients with the M184V/I mutation.

Brief Report: Comparative Analysis of Pre-existing HIV Drug Resistance Mutations in Proviral DNA Using Next-Generation Sequencing and Routine HIV RNA Genotyping

“…As previously mentioned, FTC containing regimens are known to select for the presence of M184V/I if present. 9 In our cohort, 6 of 8 (2 of 2 high-frequency and 4 of 6 low-frequency) M184V/I mutations were identified in participants with FTC-containing regimens. Moreover, we did not investigate integrase inhibitors (INSTI) because of the lack of sequencing data.…”

“…M184V and M184I are the most frequently selected NRTI mutations in persons with relapsed viremia while receiving lamivudine (3TC) or emtricitabine (FTC)-containing regimens. 9 However, the detection of transmitted M184V/I is relatively low in ART-naive persons with HIV (PWH) (7%, n = 14/204) 10 likely due to rapid reversion because of reduced replication capacity. 11 Because the rapid replacement of M184V/I is associated with known fitness costs, 12 less is known regarding whether earlier sampling time and sequencing methods are relevant to successfully detecting these mutations.…”