Protease and gag diversity and drug resistance mutations among treatment-naive Mexican people living with HIV
Abstract Introduction In Mexico, HIV genotyping is performed in people living with HIV (PLWH) failing their first-line antiretroviral (ARV) regimen; it is not routinely done for all treatment-naive PLWH before ARV initiation. The first nationally representative survey published in 2016 reported that...
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| Format: | Article |
| Language: | English |
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BMC
2022-05-01
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| Series: | BMC Infectious Diseases |
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| Online Access: | https://doi.org/10.1186/s12879-022-07446-8 |
| _version_ | 1818202168912510976 |
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| author | Samantha Climaco-Arvizu Víctor Flores-López Carolina González-Torres Francisco Javier Gaytán-Cervantes María Concepción Hernández-García Paola Berenice Zárate-Segura Monserrat Chávez-Torres Emiliano Tesoro-Cruz Sandra María Pinto-Cardoso Vilma Carolina Bekker-Méndez |
| author_facet | Samantha Climaco-Arvizu Víctor Flores-López Carolina González-Torres Francisco Javier Gaytán-Cervantes María Concepción Hernández-García Paola Berenice Zárate-Segura Monserrat Chávez-Torres Emiliano Tesoro-Cruz Sandra María Pinto-Cardoso Vilma Carolina Bekker-Méndez |
| author_sort | Samantha Climaco-Arvizu |
| collection | DOAJ |
| description | Abstract Introduction In Mexico, HIV genotyping is performed in people living with HIV (PLWH) failing their first-line antiretroviral (ARV) regimen; it is not routinely done for all treatment-naive PLWH before ARV initiation. The first nationally representative survey published in 2016 reported that the prevalence of pretreatment drug mutations in treatment-naive Mexican PLWH was 15.5% to any antiretroviral drug and 10.6% to non-nucleoside reverse transcriptase inhibitors (NNRTIs) using conventional Sanger sequencing. Most reports in Mexico focus on HIV pol gene and nucleoside and non-nucleoside reverse transcriptase inhibitor (NRTI and NNRTI) drug resistance mutations (DRMs) prevalence, using Sanger sequencing, next-generation sequencing (NGS) or both. To our knowledge, NGS has not be used to detect pretreatment drug resistance mutations (DRMs) in the HIV protease (PR) gene and its substrate the Gag polyprotein. Methods Treatment-naive adult Mexican PLWH were recruited between 2016 and 2019. HIV Gag and protease sequences were obtained by NGS and DRMs were identified using the WHO surveillance drug resistance mutation (SDRM) list. Results One hundred PLWH attending a public national reference hospital were included. The median age was 28 years-old, and most were male. The median HIV viral load was 4.99 [4.39–5.40] log copies/mL and median CD4 cell count was 150 [68.0–355.78] cells/mm3. As expected, most sequences clustered with HIV-1 subtype B (97.9%). Major PI resistance mutations were detected: 8 (8.3%) of 96 patients at a detection threshold of 1% and 3 (3.1%) at a detection threshold of 20%. A total of 1184 mutations in Gag were detected, of which 51 have been associated with resistance to PI, most of them were detected at a threshold of 20%. Follow-up clinical data was available for 79 PLWH at 6 months post-ART initiation, seven PLWH failed their first ART regimen; however no major PI mutations were identified in these individuals at baseline. Conclusions The frequency of DRM in the HIV protease was 7.3% at a detection threshold of 1% and 3.1% at a detection threshold of 20%. NGS-based HIV drug resistance genotyping provide improved detection of DRMs. Viral load was used to monitor ARV response and treatment failure was 8.9%. |
| first_indexed | 2024-12-12T03:05:10Z |
| format | Article |
| id | doaj.art-a9689374601c4134b30fc4771ddd4f4e |
| institution | Directory Open Access Journal |
| issn | 1471-2334 |
| language | English |
| last_indexed | 2024-12-12T03:05:10Z |
| publishDate | 2022-05-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Infectious Diseases |
| spelling | doaj.art-a9689374601c4134b30fc4771ddd4f4e2022-12-22T00:40:32ZengBMCBMC Infectious Diseases1471-23342022-05-0122111110.1186/s12879-022-07446-8Protease and gag diversity and drug resistance mutations among treatment-naive Mexican people living with HIVSamantha Climaco-Arvizu0Víctor Flores-López1Carolina González-Torres2Francisco Javier Gaytán-Cervantes3María Concepción Hernández-García4Paola Berenice Zárate-Segura5Monserrat Chávez-Torres6Emiliano Tesoro-Cruz7Sandra María Pinto-Cardoso8Vilma Carolina Bekker-Méndez9Unidad de Investigación Médica en Inmunología e Infectología, Hospital de Infectología “Dr Daniel Méndez Hernández”, Centro Médico Nacional “La Raza”, Instituto Mexicano del Seguro Social (IMSS)Department of Biochemistry, University of CambridgeDivisión de Desarrollo de La Investigación, Instituto Mexicano del Seguro SocialDivisión de Desarrollo de La Investigación, Instituto Mexicano del Seguro SocialInstituto Mexicano del Seguro Social (IMSS), Hospital de Infectología “Dr Daniel Méndez Hernández”, Centro Médico Nacional (CMN)Laboratorio de Medicina Traslacional, Instituto Politécnico NacionalCentro de Investigación en Enfermedades Infecciosas, Instituto Nacional de Enfermedades Respiratorias Ismael Cosío VillegasUnidad de Investigación Médica en Inmunología e Infectología, Hospital de Infectología “Dr Daniel Méndez Hernández”, Centro Médico Nacional “La Raza”, Instituto Mexicano del Seguro Social (IMSS)Centro de Investigación en Enfermedades Infecciosas, Instituto Nacional de Enfermedades Respiratorias Ismael Cosío VillegasUnidad de Investigación Médica en Inmunología e Infectología, Hospital de Infectología “Dr Daniel Méndez Hernández”, Centro Médico Nacional “La Raza”, Instituto Mexicano del Seguro Social (IMSS)Abstract Introduction In Mexico, HIV genotyping is performed in people living with HIV (PLWH) failing their first-line antiretroviral (ARV) regimen; it is not routinely done for all treatment-naive PLWH before ARV initiation. The first nationally representative survey published in 2016 reported that the prevalence of pretreatment drug mutations in treatment-naive Mexican PLWH was 15.5% to any antiretroviral drug and 10.6% to non-nucleoside reverse transcriptase inhibitors (NNRTIs) using conventional Sanger sequencing. Most reports in Mexico focus on HIV pol gene and nucleoside and non-nucleoside reverse transcriptase inhibitor (NRTI and NNRTI) drug resistance mutations (DRMs) prevalence, using Sanger sequencing, next-generation sequencing (NGS) or both. To our knowledge, NGS has not be used to detect pretreatment drug resistance mutations (DRMs) in the HIV protease (PR) gene and its substrate the Gag polyprotein. Methods Treatment-naive adult Mexican PLWH were recruited between 2016 and 2019. HIV Gag and protease sequences were obtained by NGS and DRMs were identified using the WHO surveillance drug resistance mutation (SDRM) list. Results One hundred PLWH attending a public national reference hospital were included. The median age was 28 years-old, and most were male. The median HIV viral load was 4.99 [4.39–5.40] log copies/mL and median CD4 cell count was 150 [68.0–355.78] cells/mm3. As expected, most sequences clustered with HIV-1 subtype B (97.9%). Major PI resistance mutations were detected: 8 (8.3%) of 96 patients at a detection threshold of 1% and 3 (3.1%) at a detection threshold of 20%. A total of 1184 mutations in Gag were detected, of which 51 have been associated with resistance to PI, most of them were detected at a threshold of 20%. Follow-up clinical data was available for 79 PLWH at 6 months post-ART initiation, seven PLWH failed their first ART regimen; however no major PI mutations were identified in these individuals at baseline. Conclusions The frequency of DRM in the HIV protease was 7.3% at a detection threshold of 1% and 3.1% at a detection threshold of 20%. NGS-based HIV drug resistance genotyping provide improved detection of DRMs. Viral load was used to monitor ARV response and treatment failure was 8.9%.https://doi.org/10.1186/s12879-022-07446-8Human immunodeficiency virusAntiretroviral therapyHIV drug resistance mutationsHIV genotypingGagProtease |
| spellingShingle | Samantha Climaco-Arvizu Víctor Flores-López Carolina González-Torres Francisco Javier Gaytán-Cervantes María Concepción Hernández-García Paola Berenice Zárate-Segura Monserrat Chávez-Torres Emiliano Tesoro-Cruz Sandra María Pinto-Cardoso Vilma Carolina Bekker-Méndez Protease and gag diversity and drug resistance mutations among treatment-naive Mexican people living with HIV BMC Infectious Diseases Human immunodeficiency virus Antiretroviral therapy HIV drug resistance mutations HIV genotyping Gag Protease |
| title | Protease and gag diversity and drug resistance mutations among treatment-naive Mexican people living with HIV |
| title_full | Protease and gag diversity and drug resistance mutations among treatment-naive Mexican people living with HIV |
| title_fullStr | Protease and gag diversity and drug resistance mutations among treatment-naive Mexican people living with HIV |
| title_full_unstemmed | Protease and gag diversity and drug resistance mutations among treatment-naive Mexican people living with HIV |
| title_short | Protease and gag diversity and drug resistance mutations among treatment-naive Mexican people living with HIV |
| title_sort | protease and gag diversity and drug resistance mutations among treatment naive mexican people living with hiv |
| topic | Human immunodeficiency virus Antiretroviral therapy HIV drug resistance mutations HIV genotyping Gag Protease |
| url | https://doi.org/10.1186/s12879-022-07446-8 |
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