Description of the L76V resistance protease mutation in HIV-1 B and "non-B" subtypes

PLoS One. 2013;8(1):e54381. doi: 10.1371/journal.pone.0054381. Epub 2013 Jan 18.

Abstract

Objective: To describe the prevalence of the L76V protease inhibitors resistance-associated mutation (PI-RAM) in relation with patients' characteristics and protease genotypic background in HIV-1 B- and "non-B"-infected patients.

Methods: Frequency of the L76V mutation between 1998 and 2010 was surveyed in the laboratory database of 3 clinical centers. Major PI-RAMs were identified according to the IAS-USA list. Fisher's and Wilcoxon tests were used to compare variables.

Results: Among the overall 29,643 sequences analyzed, the prevalence of L76V was 1.50%, while was 5.42% in PI-resistant viruses. Since 2008 the prevalence of L76V was higher in "non-B"-infected than in B-infected patients each year. Median time since diagnosis of HIV-1 infection and median time under antiretroviral-based regimen were both shorter in "non-B"- than in B-infected patients (8 vs 11 years, P<0.0001; and 7 vs 8 years, P = 0.004). In addition, "non-B"-infected patients had been pre-exposed to a lower number of PI (2 vs 3, P = 0.016). The L76V was also associated with a lower number of major PI-RAMs in "non-B" vs B samples (3 vs 4, P = 0.0001), and thus it was more frequent found as single major PI-RAM in "non-B" vs B subtype (10% vs 2%, P = 0.014).

Conclusions: We showed an impact of viral subtype on the selection of the L76V major PI-RAM with a higher prevalence in "non-B" subtypes observed since 2008. In addition, in "non-B"-infected patients this mutation appeared more rapidly and was associated with less PI-RAM.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Anti-HIV Agents / administration & dosage*
  • Drug Resistance, Viral / genetics*
  • Female
  • Genotype
  • HIV Infections / drug therapy
  • HIV Infections / genetics*
  • HIV Infections / virology
  • HIV Protease / genetics
  • HIV Protease Inhibitors / administration & dosage*
  • HIV-1 / drug effects
  • HIV-1 / genetics*
  • Humans
  • Male
  • Middle Aged
  • Mutation
  • Sequence Analysis, DNA

Substances

  • Anti-HIV Agents
  • HIV Protease Inhibitors
  • HIV Protease

Grants and funding

The study was supported by French National Agency for Research on AIDS and viral hepatitis (Agence Nationale de Recherches sur le SIDA et les hépatites virales [ANRS]) and from the European Community’s Seventh Framework Programme (FP7/2007–2013) under the project “Collaborative HIV and Anti-HIV Drug Resistance Network (CHAIN)” (grant no. 223131) and Aviralia Foundation. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.