Protease mutation M89I/V is linked to therapy failure in patients infected with the HIV-1 non-B subtypes C, F or G.
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.
Abecasis
Ana Barroso
AB
Rega Institute for Medical Research, Katholieke Universiteit Leuven, Leuven, Belgium. ana.abecasis@uz.kuleuven.ac.be
Deforche
Koen
K
Snoeck
Joke
J
Bacheler
Lee T
LT
McKenna
Paula
P
Carvalho
Ana Patrícia
AP
Gomes
Perpétua
P
Camacho
Ricardo Jorge
RJ
Vandamme
Anne-Mieke
AM
D000328:Adult; D000595:Amino Acid Sequence; D001499:Bayes Theorem; D024921:Drug Resistance, Multiple, Viral / Q000235:genetics; D005260:Female; D005838:Genotype; D015658:HIV Infections / Q000188:drug therapy* / Q000235:genetics; D016333:HIV Protease / Q000235:genetics*; D017320:HIV Protease Inhibitors / Q000627:therapeutic use; D015497:HIV-1 / Q000235:genetics*; D006801:Humans; D008297:Male; D009154:Mutation / Q000235:genetics*; D010641:Phenotype; D017211:Treatment Failure; D019562:Viral Load
D017320:HIV Protease Inhibitors; D016333:HIV Protease