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

Abecasis, Ana Barrosoa,d; Deforche, Koena; Snoeck, Jokea; Bacheler, Lee Tb; McKenna, Paulac; Carvalho, Ana Patríciad; Gomes, Perpétuad,e; Camacho, Ricardo Jorged; Vandamme, Anne-Miekea

Clinical Science

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.

From the aRega Institute for Medical Research, Katholieke Universiteit Leuven, Leuven, Belgium

bVircoLab, Inc, Durham North Carolina, USA

cVirco BVBA, Mechelen, Belgium

dVirology Laboratory, Hospital Egas Moniz, Lisbon

eInstituto Superior de Ciências da Saúde-Sul, Monte da Caparica, Portugal.

Received 26 June, 2005

Revised 26 July, 2005

Accepted 8 August, 2005

Correspondence to Ana Barroso Abecasis, Katholieke Universiteit Leuven, Laboratory for Clinical and Epidemiological Virology, Rega Institute for Medical Research, Minderbroedersstraat 10, B-3000 Leuven, Belgium. E-mail: ana.abecasis@uz.kuleuven.ac.be

© 2005 Lippincott Williams & Wilkins, Inc.