Skip to main content
  • Poster presentation
  • Open access
  • Published:

Clinical concentrations of efavirenz (EFV) reduce cellular proliferation and viability in several human cell lines


Efavirenz (EFV)-containing therapies have been related to several side-effects including hepatotoxic events and chronic disorders in the lipid metabolism but the possible cellular mechanisms underlying these effects have received little study.


In this work, we evaluated the cytotoxic effects of clinical (10–25 μM) and supraclinical (50 μM) concentrations of EFV in various human cellular models.


MTT assays upon 24 h of culture in the presence of the drug revealed reduced viability in the human hepatoma cell line Hep3B (significant for all three concentrations and calculated as 84.59 ± 8.82% decrease for 50 μM EFV), human cervix carcinoma cell line HeLa (71.92 ± 5.49% reduction for 50 μM EFV) and primary Human Umbilical Vein Endothelial cells (HUVEC), (96.76 ± 0.27% reduction for 50 μM EFV). This result was corroborated with 3-day-proliferation experiments in which Hep3B were exposed to different concentrations of EFV; a significant reduction (60.1 ± 6.54% after 3 days) was detected with 25 μM EFV whereas cytotoxicity (97.01 ± 1.13% reduction) was observed with 50 μM, however no changes were detected with 10 μM EFV. With the aim of analyzing the mechanisms responsible for this diminished cellular viability, we performed bivariate Annexin V/Propidium Iodide analysis of HeLa cells using static cytometry, and found that EFV-treated cells (4 and 8 h), presented features of late or advanced apoptosis. We also observed a dose-dependent translocation of two mitochondrial proapoptotic proteins, cytochrome c and AIF, in Hep3B cells after EFV-treatment (4 h), which was accompanied by a significant reduction in the mitochondrial membrane potential (Δψm), as measured by TMRM fluorescence. Confocal fluorescence microscopy experiments revealed a dose-dependent activation of caspase-3 and -9 and an absence of activation of caspase-8, pointing to EFV induction of the intrinsic (mitochondrial) apoptotic pathway.


In conclusion, clinical concentrations of EFV can be cytotoxic and lead to activation of apoptotic programmes in common cellular models. This suggests that the therapeutic range of EFV is rather narrow and also that prolonged administration of this drug may result in HAART-related mitochondrial dysfunction.


  1. Landriscina M, Fabiano A, Altamura S, Bagalà C, Piscazzi A, Cassano A, Spadafora C, Giorgino F, Barone C, Cignarelli M: Reverse transcriptase inhibitors down-regulate cell proliferation in vitro and in vivo and restore thyrotropin signaling and iodine uptake in human thyroid anaplastic carcinoma. J Clin Endocrinol Metab. 2005, 90 (10): 5663-71. 10.1210/jc.2005-0367.

    Article  PubMed  CAS  Google Scholar 

  2. El Hadri K, Glorian M, Monsempes C, Dieudonné MN, Pecquery R, Giudicelli Y, Andreani M, Dugail I, Fève B: In vitro supression of the Lipogenic pathway by the nonnucleoside reverse transcriptase inhibitor efavirenz in 3T3 and human preadipocytes and adipocytes. J Biol Chem. 2004, 279 (15): 15130-15141. 10.1074/jbc.M312875200.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations


Rights and permissions

Open Access This article is published under license to BioMed Central Ltd. This is an Open Access article is distributed under the terms of the Creative Commons Attribution 2.0 International License (, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Reprints and permissions

About this article

Cite this article

Apostolova, N., Blas-García, A., Ballesteros, D. et al. Clinical concentrations of efavirenz (EFV) reduce cellular proliferation and viability in several human cell lines. JIAS 11 (Suppl 1), P161 (2008).

Download citation

  • Published:

  • DOI: