Transmitted drug resistance to NRTIs and risk of virological failure in naïve patients treated with integrase inhibitors

HIV Med. 2021 Jan;22(1):22-27. doi: 10.1111/hiv.12956. Epub 2020 Sep 23.


Objectives: Nucleoside reverse transcriptase inhibitor (NRTI) transmitted drug resistance mutations (TDRMs) could increase the risk of virological failure (VF) of first-line integrase strand transfer inhibitor (InSTI)-based regimens.

Methods: Patients starting two NRTIs (lamivudine/emtricitabine plus abacavir/tenofovir) plus raltegravir or dolutegravir were selected from the EuResist cohort. The role of NRTI genotypic susceptibility score and of specific TDRMs in VF (i.e. two consecutive viral loads > 50 HIV-1 RNA copies/mL or a single viral load ≥ 200 copies/mL after 3 months from antiretroviral therapy start) was evaluated in the overall population and according to the InSTI employed.

Results: From 2008 to 2017, 1095 patients were eligible for the analysis (55.5% men, median age 39 years). In all, 207 VFs occurred over 1023 patient-years of follow-up. The genotypic susceptibility score (GSS) had no effect on the risk of VF in the overall population. However, the presence of M184V/I independently predicted VF of raltegravir- but not dolutegravir-based therapy when compared with a fully-active backbone [adjusted hazard ratio (aHR) = 3.09, P = 0.035], particularly when associated with other non-thymidine analogue mutations (aHR = 27.62, P = 0.004). Higher-zenith HIV-RNA and lower nadir CD4 counts independently predicted VF.

Conclusions: NRTI backbone TDRMs increased the risk of VF with raltegravir-based but not dolutegravir-based regimens.

Keywords: NRTI backbone; integrase inhibitors; naïve; raltegravir; virological failure.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Anti-HIV Agents / therapeutic use
  • Drug Resistance, Viral* / drug effects
  • Drug Resistance, Viral* / genetics
  • Female
  • HIV Infections / drug therapy*
  • HIV Infections / epidemiology
  • Humans
  • Integrase Inhibitors / therapeutic use*
  • Male
  • Raltegravir Potassium / therapeutic use*
  • Viral Load / drug effects*


  • Anti-HIV Agents
  • Integrase Inhibitors
  • Raltegravir Potassium