Characterization of drug resistance in antiretroviral-treated patients infected with HIV-1 CRF02_AG and AGK subtypes in Mali and Burkina Faso

IMPSylla M, A Chamberland, C Boileau, HA Troaré, S Ag-Aboubacrine, M Cissé, S Koala, J Drabo, I Diallo, P Niamba, D Tremblay-Sher, N Machouf, S Rashed, D Nickle, V-K Nguyen, C Tremblay for the ATARAO Group. Characterization of drug resistance in antiretroviral-treated patients infected with HIV-1 CRF02_AG and AGK subtypes in Mali and Burkina Faso. Antiviral therapy. 2008; 13 (1) 141-8.
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Abstract:
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Background: In a multicentred cohort of patients on antiretroviral therapy (ART) in  Burkina Faso and Mali, we analysed the prevalence of HIV drug resistance mutations in patients failing a modified directly observed therapy (mDOT) protocol.
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Methods: Patients on ART >6 months and with viral load (VL) >500 copies/ml were enrolled in a mDOT protocol. Genotypic resistance testing was performed on pre- and post-mDOT plasma samples of patients who still had VL >500 copies/ml after mDOT.
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Results: Eight hundred and one patients from seven sites participated in the study. One hundred and thirteen patients (14.1%) had VL >500 copies/ml. Most patients were treated with lamivudine along with zidovudine or stavudine and efavirenz or nevirapine. Genotypes were available for 46 patients. The predominant HIV-1 subtypes were CRF02_AG in 26 (56.5%) and AGK/K/AK in 12 (26.1%) patients. The prevalence of drug resistance mutations by class were as follows for nucleoside reverse transcriptase inhibitors: 184I/V (82.6%), 215Y/F (32.6%), 219E/Q (19.6%), 70R (19.6%), 67N (21.7%), 41L (15.2%) and 151M(2.2%). For non-nucleoside reverse transcriptase inhibitors the prevalence was: 103N (50%) and 181C/I (19.6%). Phylogenetic analysis showed that, although the genetic distances were small among isolates, there was no clustering of a particular subtype in a specific region and that the high prevalence of AGK subtype in our drug-resistant population was not due to a circulating resistant strain.
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Conclusion: Although CRF02_AG is the dominant clade in the Burkina Faso/Mali region, isolates with subtype K reverse transcriptase were frequent in our cohort. Drug resistance mutation pathways in subtype K reverse transcriptase need to be further  valuated in a larger cohort of non-B HIV-infected individuals.
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