Efficacy, safety and central nervous system effects after switch from efavirenz/tenofovir/emtricitabine to doravirine/tenofovir/lamivudine

AIDS. 2021 Apr 1;35(5):759-767. doi: 10.1097/QAD.0000000000002804.

Abstract

Objective: Doravirine is an alternative treatment option for individuals who do not tolerate efavirenz. We assessed efficacy, safety, and CNS effects in adults with HIV-1 and CNS complaints who switched from an efavirenz-based regimen to a doravirine-based regimen.

Design: Multicenter, double-blind, randomized trial (NCT02652260).

Methods: Virologically suppressed adults receiving efavirenz/emtricitabine/tenofovir (EFV/FTC/TDF), or its components, with ongoing EFV-associated CNS toxicity grade 2 or higher (DAIDS criteria) were switched to doravirine/lamivudine/tenofovir (DOR/3TC/TDF) on day 1 (Immediate Switch Group [ISG]) or after 12 weeks (Deferred Switch Group [DSG]). CNS toxicity data were collected by self-administered questionnaire. The primary endpoint was the proportion of participants with any grade 2 or higher CNS toxicity at week 12. Secondary endpoints included virologic response and effect on fasting lipids.

Results: Eighty-six participants (58% men, 56% black, median age 41 years, median 4 years on prior EFV regimen) were enrolled (43 ISG, 43 DSG) and included in the analyses. At week 12, 42% of ISG and 37% of DSG had at least 1 grade 2 or higher CNS toxicity [difference 4.7%, 95% CI (-16 to 25%); P = 0.33]. At 24 weeks postswitch, HIV-1 RNA less than 50 copies/ml was maintained in 95.3% of participants, and fasting lipids were significantly decreased (LDL-cholesterol -11.0, non-HDL-cholesterol -13.2, HDL-cholesterol -7.7, total cholesterol -20.9, and triglycerides -13.0 mg/dl).

Conclusion: In participants who had CNS complaints while receiving EFV/FTC/TDF, improvement in CNS toxicities attributable to EFV was not significantly different after switching to DOR/3TC/TDF compared with remaining on EFV/FTC/TDF. Virologic efficacy was maintained and lipid profiles improved after switching to DOR/3TC/TDF.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Alkynes
  • Anti-HIV Agents* / adverse effects
  • Benzoxazines
  • Central Nervous System
  • Cyclopropanes
  • Drug Combinations
  • Emtricitabine / therapeutic use
  • Female
  • HIV Infections* / drug therapy
  • Humans
  • Lamivudine / therapeutic use
  • Male
  • Pyridones
  • Tenofovir / therapeutic use
  • Treatment Outcome
  • Triazoles

Substances

  • Alkynes
  • Anti-HIV Agents
  • Benzoxazines
  • Cyclopropanes
  • Drug Combinations
  • Pyridones
  • Triazoles
  • Lamivudine
  • doravirine
  • Tenofovir
  • Emtricitabine
  • efavirenz

Associated data

  • ClinicalTrials.gov/NCT02652260