[8] POLYMORPHISM OF HIV-2 PROTEASE GENE AND SELECTION OF DRUG RESISTANCE MUTATIONS IN HIV-2 INFECTED PATIENTS INCLUDED IN THE FRENCH ANRS COHORT AND TREATED WITH PROTEASE INHIBITORS

2nd International AIDS Society Conference on HIV Pathogenesis and Treatment

Paris, France - July 13 - 16, 2003

[TITLE:] POLYMORPHISM OF HIV-2 PROTEASE GENE AND SELECTION OF DRUG RESISTANCE MUTATIONS IN HIV-2 INFECTED PATIENTS INCLUDED IN THE FRENCH ANRS COHORT AND TREATED WITH PROTEASE INHIBITORS

[AUTHOR(S):] D Descamps¹, S Matheron¹, F Damond¹, G Peytavin¹, P Campa¹, S Pueyo², F Mammano¹, S Lastere¹, I Farfara¹, F Simon³, G Chene² and F Brun-Vezinet¹ for the French HIV-2 ANRS cohort
¹Hopital Bichat-Claude Bernard, Paris, France; ²Inserm U330, Bordeaux, France; and ³Institut Pasteur, Dakar, Sénégal

IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd: Abstract No. 8
Antiviral Therapy 2003; 8(Suppl. 1):S187

[ABSTRACT:] Background: To characterize the polymorphism of HIV-2 protease gene and the mutations selected in the protease gene in HIV-2 infected patients (pts) receiving protease inhibitors (PI).

Methods: Protease gene from plasma specimens of 94 naïve pts was sequenced to study polymorphism. Selection of resistance mutations was analyzed in 30 pts having received PI therapy for a median of 12 months. Plasma PI concentrations were determined by HPLC assays.

Results: Of the 94 pts, 68 were infected by an HIV-2 subtype A, 25 by a subtype B and 1 by a subtype C. According to Los Alamos database, 55 out of 99 amino acids vary between HIV-1 clade B and HIV-2 protease genes. Two out these 55 positions, I46 and I82, are known to be involved in HIV-1 resistance. Substitution L90M, described as major resistance mutation for HIV-1, was observed in one isolate infected with an HIV-2 subtype A. Amplification of protease gene was successful in 17 out of the 30 treated pts. During first line PI therapy 8 pts had viruses harboring I82F (n=4) and L90M (n=4) mutations already described as associated with HIV-1 resistance. One patient had virus with both mutations. Two pts had virus with amino acid substitution not described in HIV-1 at codons 48 and 82. In 3/6 pts receiving a second line PI regimen, I84V mutation, associated with HIV-1 resistance, was selected additionally to substitutions previously selected at codons 82 and or 90. One patient selected I84L substitution. Substitutions of unknown impact were observed in all but 3 pts remaining wild-type during the follow-up. All pts receiving NFV had adequate PI plasma concentrations. Low or undetectable PI plasma concentrations were observed in pts receiving RTV (n=1), RTV/SQV (n=1), SQV alone (n=2) and IDV (n=3), respectively.

Conclusions: Mutations associated with HIV-1 PI resistance were detected in HIV-2 treated pts. Substitutions of amino acids of currently unknown impact need to be evaluated by in vitro experiments.

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