Detection of ARV-Resistant Mutants in HIV-1-Infected Individuals in a Context of Systematic Switching to an Association Based on Dolutegravir in Abidjan, Côte d’Ivoire  

作　　者：Odegue Kpadraux Danielle Kakou-Ngazoa Solange Dechi Jean-Jacques Renaud Diallo Zelica Sina Kouamé Mireille Sylla Aboubacar Tossea Koui Stéphane Kouakou Venance Adagba Marius Apia N’Chouo Kouamé Basile Touré Offianan André Dosso Mireille Odegue Kpadraux Danielle;Kakou-Ngazoa Solange;Dechi Jean-Jacques Renaud;Diallo Zelica;Sina Kouamé Mireille;Sylla Aboubacar;Tossea Koui Stéphane;Kouakou Venance;Adagba Marius;Apia N’Chouo Kouamé Basile;Touré Offianan André;Dosso Mireille(Molecular Biology Platform, Institut Pasteur, Abidjan, Cte dIvoire;Laboratory of the Regional Blood Transfusion Center, Yamoussoukro, Cte dIvoire;Department of Infectious and Tropical Diseases, University Hospital Treichville, Abidjan, Cte dIvoire;Laboratory of the Regional Blood Transfusion Center, San-Pdro, Cte dIvoire;Department of Epidemic Virus, Institut Pasteur, Abidjan, Cte dIvoire;Department of Parasitology Mycology, Institut Pasteur, Abidjan, Cte dIvoire;Department of Bacteriology-Virology, Institut Pasteur, Abidjan, Cte dIvoire)

机构地区：[1]Molecular Biology Platform, Institut Pasteur, Abidjan, Cte dIvoire [2]Laboratory of the Regional Blood Transfusion Center, Yamoussoukro, Cte dIvoire [3]Department of Infectious and Tropical Diseases, University Hospital Treichville, Abidjan, Cte dIvoire [4]Laboratory of the Regional Blood Transfusion Center, San-Pdro, Cte dIvoire [5]Department of Epidemic Virus, Institut Pasteur, Abidjan, Cte dIvoire [6]Department of Parasitology Mycology, Institut Pasteur, Abidjan, Cte dIvoire [7]Department of Bacteriology-Virology, Institut Pasteur, Abidjan, Cte dIvoire

出　　处：《American Journal of Molecular Biology》2024年第3期138-151,共14页美国分子生物学期刊（英文）

摘　　要：The emergence of antiretroviral resistance mutations represents a major threat to the achievement of national and global goals for the elimination of HIV-1 infection. The global strategy in 2019 in Cte d'Ivoire is a new national policy for the management of people living with HIV with the administration of dolutegravir (DTG)-based fixed-dose combination. The aim of our study was to evaluate HIV-1 resistance to antiretrovirals (ARVs) in infected adult subjects in Cte d’Ivoire in the context of a systematic switch to a DTG-based combination. Between February 2022 and October 2023, a cross-sectional survey with random sampling was conducted in 06 services caring for people living with HIV. A total of 139 participants were included in the study. Adults with a viral load ≥ 1000 copies/mL were tested for HIV-1 ARV resistance mutations. Molecular analyses were performed using protocol of ANRS-MIE (National Agency for Research on AIDS and emerging infectious diseases). The interpretation is performed by HIVGRAD (https://www.hiv-grade.de/cms/grade/). The frequencies of HIV-1 resistance to non-nucleotide reverse transcriptase inhibitors (NNRTIs), nucleotide reverse transcriptase inhibitors (NRTIs), integrase inhibitors (IINTs) and protease inhibitors (PIs) were 82%, 73%, 19% and 11% respectively. The main mutations observed in the different classes were K103N (45%), M184V (64%), E157Q (19%) and L10V/M46I/A71V/I54V (6%) respectively. This study reveals the emergence of resistance to DTG-based fixed-dose combinations, favored by high rates of resistance to NRTIs and NNRTIs. This finding underlines the need for enhanced viral load monitoring and HIV-1 genotyping tests to guide the choice of NRTIs for combination therapy. In addition, monitoring for mutations to second-generation NRTIs is essential, given the scale-up of DTG-based regimens currently underway in Cte d’Ivoire.The emergence of antiretroviral resistance mutations represents a major threat to the achievement of national and global goals for the elimination of HIV-1 infection. The global strategy in 2019 in Cte d'Ivoire is a new national policy for the management of people living with HIV with the administration of dolutegravir (DTG)-based fixed-dose combination. The aim of our study was to evaluate HIV-1 resistance to antiretrovirals (ARVs) in infected adult subjects in Cte d’Ivoire in the context of a systematic switch to a DTG-based combination. Between February 2022 and October 2023, a cross-sectional survey with random sampling was conducted in 06 services caring for people living with HIV. A total of 139 participants were included in the study. Adults with a viral load ≥ 1000 copies/mL were tested for HIV-1 ARV resistance mutations. Molecular analyses were performed using protocol of ANRS-MIE (National Agency for Research on AIDS and emerging infectious diseases). The interpretation is performed by HIVGRAD (https://www.hiv-grade.de/cms/grade/). The frequencies of HIV-1 resistance to non-nucleotide reverse transcriptase inhibitors (NNRTIs), nucleotide reverse transcriptase inhibitors (NRTIs), integrase inhibitors (IINTs) and protease inhibitors (PIs) were 82%, 73%, 19% and 11% respectively. The main mutations observed in the different classes were K103N (45%), M184V (64%), E157Q (19%) and L10V/M46I/A71V/I54V (6%) respectively. This study reveals the emergence of resistance to DTG-based fixed-dose combinations, favored by high rates of resistance to NRTIs and NNRTIs. This finding underlines the need for enhanced viral load monitoring and HIV-1 genotyping tests to guide the choice of NRTIs for combination therapy. In addition, monitoring for mutations to second-generation NRTIs is essential, given the scale-up of DTG-based regimens currently underway in Cte d’Ivoire.

关 键 词：Resistant Mutants Dolutegravir HIV-1 ANTIRETROVIRALS Côte d’Ivoire 

分 类 号：R51[医药卫生—内科学]