Prediction of Coreceptor Tropism in HIV-1 Subtype C in Botswana
It remains unknown whether the C-C motif chemokine receptor type 5 (CCR5) coreceptor is still the predominant coreceptor used by Human Immunodeficiency Virus-1 (HIV-1) in Botswana, where the HIV-1 subtype C predominates. We sought to determine HIV-1C tropism in Botswana using genotypic tools, taking...
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MDPI AG
2023-01-01
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| Series: | Viruses |
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| Online Access: | https://www.mdpi.com/1999-4915/15/2/403 |
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| author | Kenanao Kotokwe Sikhulile Moyo Melissa Zahralban-Steele Molly Pretorius Holme Pinkie Melamu Catherine Kegakilwe Koofhethile Wonderful Tatenda Choga Terence Mohammed Tapiwa Nkhisang Baitshepi Mokaleng Dorcas Maruapula Tsotlhe Ditlhako Ontlametse Bareng Patrick Mokgethi Corretah Boleo Joseph Makhema Shahin Lockman Max Essex Manon Ragonnet-Cronin Vlad Novitsky Simani Gaseitsiwe PANGEA Consortium |
| author_facet | Kenanao Kotokwe Sikhulile Moyo Melissa Zahralban-Steele Molly Pretorius Holme Pinkie Melamu Catherine Kegakilwe Koofhethile Wonderful Tatenda Choga Terence Mohammed Tapiwa Nkhisang Baitshepi Mokaleng Dorcas Maruapula Tsotlhe Ditlhako Ontlametse Bareng Patrick Mokgethi Corretah Boleo Joseph Makhema Shahin Lockman Max Essex Manon Ragonnet-Cronin Vlad Novitsky Simani Gaseitsiwe PANGEA Consortium |
| author_sort | Kenanao Kotokwe |
| collection | DOAJ |
| description | It remains unknown whether the C-C motif chemokine receptor type 5 (CCR5) coreceptor is still the predominant coreceptor used by Human Immunodeficiency Virus-1 (HIV-1) in Botswana, where the HIV-1 subtype C predominates. We sought to determine HIV-1C tropism in Botswana using genotypic tools, taking into account the effect of antiretroviral treatment (ART) and virologic suppression. HIV-1 gp120 V3 loop sequences from 5602 participants were analyzed for viral tropism using three coreceptor use predicting algorithms/tools: Geno2pheno, HIV-1C Web Position-Specific Score Matrices (WebPSSM) and the 11/25 charge rule. We then compared the demographic and clinical characteristics of people living with HIV (PLWH) harboring R5- versus X4-tropic viruses using χ<sup>2</sup> and Wilcoxon rank sum tests for categorical and continuous data analysis, respectively. The three tools congruently predicted 64% of viruses as either R5-tropic or X4-tropic. Geno2pheno and the 11/25 charge rule had the highest concordance at 89%. We observed a significant difference in ART status between participants harboring X4- versus R5-tropic viruses. X4-tropic viruses were more frequent among PLWH receiving ART (χ<sup>2</sup> test, <i>p</i> = 0.03). CCR5 is the predominant coreceptor used by HIV-1C strains circulating in Botswana, underlining the strong potential for CCR5 inhibitor use, even in PLWH with drug resistance. We suggest that the tools for coreceptor prediction should be used in combination. |
| first_indexed | 2024-03-11T08:00:56Z |
| format | Article |
| id | doaj.art-9cefb75749aa4c4c86d4b9634b1e4947 |
| institution | Directory Open Access Journal |
| issn | 1999-4915 |
| language | English |
| last_indexed | 2024-03-11T08:00:56Z |
| publishDate | 2023-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Viruses |
| spelling | doaj.art-9cefb75749aa4c4c86d4b9634b1e49472023-11-16T23:48:32ZengMDPI AGViruses1999-49152023-01-0115240310.3390/v15020403Prediction of Coreceptor Tropism in HIV-1 Subtype C in BotswanaKenanao Kotokwe0Sikhulile Moyo1Melissa Zahralban-Steele2Molly Pretorius Holme3Pinkie Melamu4Catherine Kegakilwe Koofhethile5Wonderful Tatenda Choga6Terence Mohammed7Tapiwa Nkhisang8Baitshepi Mokaleng9Dorcas Maruapula10Tsotlhe Ditlhako11Ontlametse Bareng12Patrick Mokgethi13Corretah Boleo14Joseph Makhema15Shahin Lockman16Max Essex17Manon Ragonnet-Cronin18Vlad Novitsky19Simani Gaseitsiwe20PANGEA ConsortiumBotswana Harvard AIDS Institute Partnership, Princess Marina Hospital, Gaborone, BotswanaBotswana Harvard AIDS Institute Partnership, Princess Marina Hospital, Gaborone, BotswanaDepartment of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health, Harvard University, Boston, MA 02115, USADepartment of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health, Harvard University, Boston, MA 02115, USABotswana Harvard AIDS Institute Partnership, Princess Marina Hospital, Gaborone, BotswanaBotswana Harvard AIDS Institute Partnership, Princess Marina Hospital, Gaborone, BotswanaBotswana Harvard AIDS Institute Partnership, Princess Marina Hospital, Gaborone, BotswanaBotswana Harvard AIDS Institute Partnership, Princess Marina Hospital, Gaborone, BotswanaDepartment of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health, Harvard University, Boston, MA 02115, USABotswana Harvard AIDS Institute Partnership, Princess Marina Hospital, Gaborone, BotswanaBotswana Harvard AIDS Institute Partnership, Princess Marina Hospital, Gaborone, BotswanaBotswana Harvard AIDS Institute Partnership, Princess Marina Hospital, Gaborone, BotswanaBotswana Harvard AIDS Institute Partnership, Princess Marina Hospital, Gaborone, BotswanaBotswana Harvard AIDS Institute Partnership, Princess Marina Hospital, Gaborone, BotswanaBotswana Harvard AIDS Institute Partnership, Princess Marina Hospital, Gaborone, BotswanaBotswana Harvard AIDS Institute Partnership, Princess Marina Hospital, Gaborone, BotswanaBotswana Harvard AIDS Institute Partnership, Princess Marina Hospital, Gaborone, BotswanaBotswana Harvard AIDS Institute Partnership, Princess Marina Hospital, Gaborone, BotswanaDepartment of Ecology and Evolution, The University of Chicago, Chicago, IL 60637, USABotswana Harvard AIDS Institute Partnership, Princess Marina Hospital, Gaborone, BotswanaBotswana Harvard AIDS Institute Partnership, Princess Marina Hospital, Gaborone, BotswanaIt remains unknown whether the C-C motif chemokine receptor type 5 (CCR5) coreceptor is still the predominant coreceptor used by Human Immunodeficiency Virus-1 (HIV-1) in Botswana, where the HIV-1 subtype C predominates. We sought to determine HIV-1C tropism in Botswana using genotypic tools, taking into account the effect of antiretroviral treatment (ART) and virologic suppression. HIV-1 gp120 V3 loop sequences from 5602 participants were analyzed for viral tropism using three coreceptor use predicting algorithms/tools: Geno2pheno, HIV-1C Web Position-Specific Score Matrices (WebPSSM) and the 11/25 charge rule. We then compared the demographic and clinical characteristics of people living with HIV (PLWH) harboring R5- versus X4-tropic viruses using χ<sup>2</sup> and Wilcoxon rank sum tests for categorical and continuous data analysis, respectively. The three tools congruently predicted 64% of viruses as either R5-tropic or X4-tropic. Geno2pheno and the 11/25 charge rule had the highest concordance at 89%. We observed a significant difference in ART status between participants harboring X4- versus R5-tropic viruses. X4-tropic viruses were more frequent among PLWH receiving ART (χ<sup>2</sup> test, <i>p</i> = 0.03). CCR5 is the predominant coreceptor used by HIV-1C strains circulating in Botswana, underlining the strong potential for CCR5 inhibitor use, even in PLWH with drug resistance. We suggest that the tools for coreceptor prediction should be used in combination.https://www.mdpi.com/1999-4915/15/2/403CCR5CXCR4R5-tropic virusesX4-tropic virusesHIV-1C tropism |
| spellingShingle | Kenanao Kotokwe Sikhulile Moyo Melissa Zahralban-Steele Molly Pretorius Holme Pinkie Melamu Catherine Kegakilwe Koofhethile Wonderful Tatenda Choga Terence Mohammed Tapiwa Nkhisang Baitshepi Mokaleng Dorcas Maruapula Tsotlhe Ditlhako Ontlametse Bareng Patrick Mokgethi Corretah Boleo Joseph Makhema Shahin Lockman Max Essex Manon Ragonnet-Cronin Vlad Novitsky Simani Gaseitsiwe PANGEA Consortium Prediction of Coreceptor Tropism in HIV-1 Subtype C in Botswana Viruses CCR5 CXCR4 R5-tropic viruses X4-tropic viruses HIV-1C tropism |
| title | Prediction of Coreceptor Tropism in HIV-1 Subtype C in Botswana |
| title_full | Prediction of Coreceptor Tropism in HIV-1 Subtype C in Botswana |
| title_fullStr | Prediction of Coreceptor Tropism in HIV-1 Subtype C in Botswana |
| title_full_unstemmed | Prediction of Coreceptor Tropism in HIV-1 Subtype C in Botswana |
| title_short | Prediction of Coreceptor Tropism in HIV-1 Subtype C in Botswana |
| title_sort | prediction of coreceptor tropism in hiv 1 subtype c in botswana |
| topic | CCR5 CXCR4 R5-tropic viruses X4-tropic viruses HIV-1C tropism |
| url | https://www.mdpi.com/1999-4915/15/2/403 |
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