title: Characterization of protease resistance-associated mutations in HIV type 1 drug-naive patients following the increasing prevalence of the CRF02_AG strain in Morocco.
abstract: The purpose of this study was to investigate the amino acid substitutions in the protease of HIV-1 B and non-B subtypes and evaluate whether the emergence of resistance-associated mutations (RAMs) could have a significant correlation with the increasing prevalence of CRF02_AG strains in Morocco. A total of 162 protease gene sequences were successfully amplified from drug-naive HIV-1-infected individuals. We identified eight (sub)subtypes and CRFs: B(66%), A1(3.7%), C(1.2%), F1(0.6%), F2(0.6%), G(1.2%), CRF02_AG(25.3%), and CRF01_AE(1.2%). Phylogenetic analysis of CRF02_AG strains showed that 9.8% of isolates had a closer connection with reference strains from Morocco and 15.4% clustered with reference strains from eight West African and three European countries. When compared to the B subtype, patients with the CRF02_AG strain had a significantly higher prevalence of mutations associated with resistance to some antiprotease drugs, mainly tipranavir (TPV): H69K (97% vs. 5%; p<0.0001), L89M (95% vs. 1%; p<0.0001), and M36I/L (93% vs. 44%; p<0.0001). Most of the CRF02_AG strains (97%) significantly showed at least two TPV-RAMs (p=0.002) compared to the B subtype (7%). Multivariate analysis revealed that CRF02_AG infection was the only factor highly associated with the occurrence of more than two TPV-RAMs (C=0.42; p<0.0001). These results support the importance of transmitted drug resistance mutations (M36I/L, H69K, and L89M) in the protease gene of HIV-1 CRF02_AG isolates. This HIV drug resistance transmission before protease inhibitor (PI) exposure raises concern about its influence on the susceptibility of CRF02_AG strains to some PIs, especially tipranavir, which will soon be introduced as part of the second line therapeutic regimens in Morocco.
authors.affiliation: Laboratoire de Virologie, Institut Pasteur du Maroc, Casablanca, Morocco. lamia_miri@yahoo.fr
authors.forename: Lamia
authors.initials: L
authors.lastname: Miri
authors.forename: Ahd
authors.initials: A
authors.lastname: Ouladlahsen
authors.forename: Anass
authors.initials: A
authors.lastname: Kettani
authors.forename: Rajaa
authors.initials: R
authors.lastname: Bensghir
authors.forename: Kamal
authors.initials: K
authors.lastname: Marhoum Elfilali
authors.forename: Lahcen
authors.initials: L
authors.lastname: Wakrim
mesh_terms: D000293:Adolescent; D000328:Adult; D000465:Algorithms; D024882:Drug Resistance, Viral / Q000235:genetics*; D005260:Female; D017320:HIV Protease Inhibitors / Q000494:pharmacology*; D006679:HIV Seropositivity / Q000188:drug therapy / Q000453:epidemiology / Q000235:genetics*; D015497:HIV-1 / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009018:Morocco / Q000453:epidemiology; D009154:Mutation; D010802:Phylogeny; D015995:Prevalence; D020133:Reverse Transcriptase Polymerase Chain Reaction; D055815:Young Adult
chemical_list: D017320:HIV Protease Inhibitors