Protease mutation M89I/V is linked to therapy failure in patients infected with the HIV-1 non-B subtypes C, F or G

AIDS. 2005 Nov 4;19(16):1799-806. doi: 10.1097/01.aids.0000188422.95162.b7.


Objective: To investigate whether and how mutations at position 89 of HIV-1 protease were associated with protease inhibitor (PI) failure, and what is the impact of the HIV-1 subtype.

Methods: In a database containing pol nucleotide sequences and treatment history, the correlation between PI experience and mutations at codon 89 was determined separately for subtype B and several non-B subtypes. A Bayesian network model was used to map the resistance pathways in which M89I/V is involved for subtype G. The phenotypic effect of M89I/V for several PIs was also measured.

Results: The analysis showed that for the subtypes C, F and G in which the wild-type codon at 89 was M compared to L for subtype B, M89I/V was significantly more frequently observed in PI-treated patients displaying major resistance mutations to PIs than in drug-naive patients. M89I/V was strongly associated with PI resistance mutations at codons 71, 74 and 90. Phenotypically, M89I/V alone did not confer a reduced susceptibility to PIs. However, when combined with L90M, a significantly reduced susceptibility to nelfinavir was observed (P < 0.05) in comparison with strains with L90M alone.

Conclusions: The results of the present study show that M89I/V is associated with PI experience in subtypes C, F and G but not in subtype B. M89I/V should be considered a secondary PI mutation with an important effect on nelfinavir susceptibility in the presence of L90M.

Publication types

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

MeSH terms

  • Adult
  • Amino Acid Sequence
  • Bayes Theorem
  • Drug Resistance, Multiple, Viral / genetics
  • Female
  • Genotype
  • HIV Infections / drug therapy*
  • HIV Infections / genetics
  • HIV Protease / genetics*
  • HIV Protease Inhibitors / therapeutic use
  • HIV-1 / genetics*
  • Humans
  • Male
  • Mutation / genetics*
  • Phenotype
  • Treatment Failure
  • Viral Load


  • HIV Protease Inhibitors
  • HIV Protease