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

• Published in: Antiviral therapy Vol. 13; no. 1; pp. 141 - 148
• Main Authors: SYLLA, Mohamed, CHAMBERLAND, Annie, TREMBLAY-SHER, Daniel, MACHOUF, Nima, RASHED, Sélim, NICKLE, David C, NGUYEN, Vinh-Kim, TREMBLAY, Cécile L, BOILEAU, Catherine, TRAORE, Hamar A, AG-ABOUBACRINE, Souleyman, CISSE, Mamadou, KOALA, Samual, DRABO, Joseph, DIALLO, Ismael, NIAMBA, Pascal
• Format: Journal Article
• Language: English
• Published: London International Medical Press 2008
• Subjects: Adult; Anti-HIV Agents - therapeutic use; Antibiotics. Antiinfectious agents. Antiparasitic agents; Antiviral agents; Biological and medical sciences; Burkina Faso - epidemiology; Drug Resistance, Viral; Female; HIV Infections - drug therapy; HIV Infections - epidemiology; HIV Infections - virology; HIV-1 - genetics; Human immunodeficiency virus 1; Human viral diseases; Humans; Immunodeficiencies; Immunodeficiencies. Immunoglobulinopathies; Immunopathology; Infectious diseases; Male; Mali - epidemiology; Medical sciences; Mutation; Pharmacology. Drug treatments; Phylogeny; Viral diseases; Viral diseases of the lymphoid tissue and the blood. Aids; Mali; Burkina Faso; Africa; Human; Immunopathology; Antiretroviral agent; Treatment resistance; Typing; HIV-1 virus; Retroviridae; AIDS; Immune deficiency; Lentivirus; Infection; Virus; Viral disease; Antiviral; Human immunodeficiency virus; Subtype
• ISSN: 1359-6535; 2040-2058
• DOI: 10.1177/135965350801300116

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. 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. 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 CRFO2_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: 1841/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. Although CRFO2_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 evaluated in a larger cohort of non-B HIV-infected individuals.