@article{Cindi9000,
abstract = {Background: Excessive weight gain affects some HIV-positive individuals prescribed dolutegravir- containing regimens. Mechanisms underlying such weight gain are unknown. Setting: Data and DNA from antiretroviral therapy-na{\"{i}}ve participants who were randomized to initiate dolutegravir with emtricitabine plus either tenofovir alafenamide (TAF) or tenofovir disoproxil fumarate (TDF) in the ADVANCE study (NCT03122262) were used to characterize associations between human genetic polymorphisms and magnitude of weight gain. Methods: Associations with percent weight gain from baseline to week 48 were assessed using multivariable linear regression models. Primary analyses a priori considered 59 polymorphisms and 10 genes of potential relevance to dolutegravir, TAF or TDF pharmacokinetics. We also explored genome-wide associations. Results: Among the 314 (92{\%}) of 340 dolutegravir recipients who were successfully genotyped, 160 (47{\%}) and 154 (45{\%}) were randomized to TAF/emtricitabine and TDF/emtricitabine, respectively. In target gene analyses, the lowest P-values for the dolutegravir and tenofovir groups were ABCG2 rs4148149 (P = 7.0x10-4) and ABCC10 rs67861980 (P = 1.0x10-2), respectively, which were not significant after correction for multiple testing. In genome-wide analyses the lowest P-values for dolutegravir, was rs7590091 in TMEM163 (P = 3.7x10-8), rs17137701 in LOC105379130 (P = 6.4x10- 8) for TAF, and rs76771105 in LOC105371716 (P = 9.7x10-8) for TDF. Conclusion: Among South African participants in a randomized clinical trial of dolutegravir plus either TAF/emtricitabine or TDF/emtricitabine, we identified several potential genetic associations with weight gain. Only TMEM163 rs7590091 withstood correction for multiple testing. These associations warrant replication in other cohorts. Corresponding Author: Phumla Sinxadi. Division of Clinical Pharmacology, Department of Medicine. K45-47 Old Main Building, Groote Schuur Hospital, Observatory, 7925, Cape Town, South Africa. Tel: +27 21 650 4096; email phumla.sinxadi@uct.ac.za Conflicts of Interests and Source of Funding: The authors declare no potential conflicts of interest related to this work. Research reported in this publication was supported by the Fogarty International Center of the National Institutes of Health (NIH) under Award Number D43 TW010559. Furthermore, this work was supported by National Research Foundation through the Thuthuka Grant [113983] and Black Academic Advancement Program grant [120647], the South African Medical Research Council (SAMRC) through self-initiated research grant (PS), the Wellcome Trust (WT) through an investigator award [212265/Z/18/Z], the National Research Foundation (NRF) of South Africa (Grant Number 119078), and core funding for the Wellcome Centre for Infectious Diseases Research in Africa [203135/Z/16/Z] (GM). Grant support included TW010559, AI110527, AI077505, TR000445 and AI110527 (DWH). Gilead Sciences and ViiV Healthcare donated study drugs for the conduct of the parent study. FV reports grants from USAID, Unitaid, SAMRC, and ViiV; personal fees and non-financial support from ViiV Healthcare and Gilead Sciences, during the conduct of the study; and personal fees from Mylan, Merck, Adcock-Ingram, Aspen, Abbott, Roche, and Johnson and Johnson, outside the submitted work. SS reports grants from USAID, Unitaid, SAMRC, and ViiV Healthcare during the conduct of the study. NC reports grants from USAID, Unitaid, SAMRC and ViiV Healthcare during the conduct of the study. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH, WT, NRF, SAMRC or other funders. Copyright {\textcopyright} 2021 Wolters Kluwer Health, Inc. All rights reserved.},
author = {Cindi, Zinhle and Maartens, Gary and Bradford, Yuki and Venter, Francois and Sokhela, Simiso and Chandiwana, Nomathemba and Haas, David W and Sinxadi, Phumla},
doi = {10.1097/QAI.0000000000002661},
file = {:C$\backslash$:/Users/01462563/AppData/Local/Mendeley Ltd./Mendeley Desktop/Downloaded/Cindi et al. - 2021 - Genetic associations with weight gain among South Africans who initiated dolutegravir- and tenofovir-containing re.pdf:pdf},
issn = {1525-4135},
journal = {JAIDS Journal of Acquired Immune Deficiency Syndromes},
keywords = {Weight gain,dolutegravir,fund{\_}ack,original,pharmacogenetics,tenofovir},
mendeley-tags = {fund{\_}ack,original},
number = {3},
pages = {1002--1009},
pmid = {33625064},
title = {{Genetic associations with weight gain among South Africans who initiated dolutegravir- and tenofovir-containing regimens}},
url = {https://journals.lww.com/jaids/Fulltext/9000/Genetic{\_}Associations{\_}with{\_}Weight{\_}Gain{\_}among{\_}South.95930.aspx},
volume = {87},
year = {2021}
}

{"_id":"4i4fCBHN6sS6N2yTd","bibbaseid":"cindi-maartens-bradford-venter-sokhela-chandiwana-haas-sinxadi-geneticassociationswithweightgainamongsouthafricanswhoinitiateddolutegravirandtenofovircontainingregimens-2021","author_short":["Cindi, Z.","Maartens, G.","Bradford, Y.","Venter, F.","Sokhela, S.","Chandiwana, N.","Haas, D. W","Sinxadi, P."],"bibdata":{"bibtype":"article","type":"article","abstract":"Background: Excessive weight gain affects some HIV-positive individuals prescribed dolutegravir- containing regimens. Mechanisms underlying such weight gain are unknown. Setting: Data and DNA from antiretroviral therapy-naïve participants who were randomized to initiate dolutegravir with emtricitabine plus either tenofovir alafenamide (TAF) or tenofovir disoproxil fumarate (TDF) in the ADVANCE study (NCT03122262) were used to characterize associations between human genetic polymorphisms and magnitude of weight gain. Methods: Associations with percent weight gain from baseline to week 48 were assessed using multivariable linear regression models. Primary analyses a priori considered 59 polymorphisms and 10 genes of potential relevance to dolutegravir, TAF or TDF pharmacokinetics. We also explored genome-wide associations. Results: Among the 314 (92%) of 340 dolutegravir recipients who were successfully genotyped, 160 (47%) and 154 (45%) were randomized to TAF/emtricitabine and TDF/emtricitabine, respectively. In target gene analyses, the lowest P-values for the dolutegravir and tenofovir groups were ABCG2 rs4148149 (P = 7.0x10-4) and ABCC10 rs67861980 (P = 1.0x10-2), respectively, which were not significant after correction for multiple testing. In genome-wide analyses the lowest P-values for dolutegravir, was rs7590091 in TMEM163 (P = 3.7x10-8), rs17137701 in LOC105379130 (P = 6.4x10- 8) for TAF, and rs76771105 in LOC105371716 (P = 9.7x10-8) for TDF. Conclusion: Among South African participants in a randomized clinical trial of dolutegravir plus either TAF/emtricitabine or TDF/emtricitabine, we identified several potential genetic associations with weight gain. Only TMEM163 rs7590091 withstood correction for multiple testing. These associations warrant replication in other cohorts. Corresponding Author: Phumla Sinxadi. Division of Clinical Pharmacology, Department of Medicine. K45-47 Old Main Building, Groote Schuur Hospital, Observatory, 7925, Cape Town, South Africa. Tel: +27 21 650 4096; email phumla.sinxadi@uct.ac.za Conflicts of Interests and Source of Funding: The authors declare no potential conflicts of interest related to this work. Research reported in this publication was supported by the Fogarty International Center of the National Institutes of Health (NIH) under Award Number D43 TW010559. Furthermore, this work was supported by National Research Foundation through the Thuthuka Grant [113983] and Black Academic Advancement Program grant [120647], the South African Medical Research Council (SAMRC) through self-initiated research grant (PS), the Wellcome Trust (WT) through an investigator award [212265/Z/18/Z], the National Research Foundation (NRF) of South Africa (Grant Number 119078), and core funding for the Wellcome Centre for Infectious Diseases Research in Africa [203135/Z/16/Z] (GM). Grant support included TW010559, AI110527, AI077505, TR000445 and AI110527 (DWH). Gilead Sciences and ViiV Healthcare donated study drugs for the conduct of the parent study. FV reports grants from USAID, Unitaid, SAMRC, and ViiV; personal fees and non-financial support from ViiV Healthcare and Gilead Sciences, during the conduct of the study; and personal fees from Mylan, Merck, Adcock-Ingram, Aspen, Abbott, Roche, and Johnson and Johnson, outside the submitted work. SS reports grants from USAID, Unitaid, SAMRC, and ViiV Healthcare during the conduct of the study. NC reports grants from USAID, Unitaid, SAMRC and ViiV Healthcare during the conduct of the study. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH, WT, NRF, SAMRC or other funders. Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.","author":[{"propositions":[],"lastnames":["Cindi"],"firstnames":["Zinhle"],"suffixes":[]},{"propositions":[],"lastnames":["Maartens"],"firstnames":["Gary"],"suffixes":[]},{"propositions":[],"lastnames":["Bradford"],"firstnames":["Yuki"],"suffixes":[]},{"propositions":[],"lastnames":["Venter"],"firstnames":["Francois"],"suffixes":[]},{"propositions":[],"lastnames":["Sokhela"],"firstnames":["Simiso"],"suffixes":[]},{"propositions":[],"lastnames":["Chandiwana"],"firstnames":["Nomathemba"],"suffixes":[]},{"propositions":[],"lastnames":["Haas"],"firstnames":["David","W"],"suffixes":[]},{"propositions":[],"lastnames":["Sinxadi"],"firstnames":["Phumla"],"suffixes":[]}],"doi":"10.1097/QAI.0000000000002661","file":":C$\\$:/Users/01462563/AppData/Local/Mendeley Ltd./Mendeley Desktop/Downloaded/Cindi et al. - 2021 - Genetic associations with weight gain among South Africans who initiated dolutegravir- and tenofovir-containing re.pdf:pdf","issn":"1525-4135","journal":"JAIDS Journal of Acquired Immune Deficiency Syndromes","keywords":"Weight gain,dolutegravir,fund_ack,original,pharmacogenetics,tenofovir","mendeley-tags":"fund_ack,original","number":"3","pages":"1002–1009","pmid":"33625064","title":"Genetic associations with weight gain among South Africans who initiated dolutegravir- and tenofovir-containing regimens","url":"https://journals.lww.com/jaids/Fulltext/9000/Genetic\\_Associations\\_with\\_Weight\\_Gain\\_among\\_South.95930.aspx","volume":"87","year":"2021","bibtex":"@article{Cindi9000,\r\nabstract = {Background: Excessive weight gain affects some HIV-positive individuals prescribed dolutegravir- containing regimens. Mechanisms underlying such weight gain are unknown. Setting: Data and DNA from antiretroviral therapy-na{\\\"{i}}ve participants who were randomized to initiate dolutegravir with emtricitabine plus either tenofovir alafenamide (TAF) or tenofovir disoproxil fumarate (TDF) in the ADVANCE study (NCT03122262) were used to characterize associations between human genetic polymorphisms and magnitude of weight gain. Methods: Associations with percent weight gain from baseline to week 48 were assessed using multivariable linear regression models. Primary analyses a priori considered 59 polymorphisms and 10 genes of potential relevance to dolutegravir, TAF or TDF pharmacokinetics. We also explored genome-wide associations. Results: Among the 314 (92{\\%}) of 340 dolutegravir recipients who were successfully genotyped, 160 (47{\\%}) and 154 (45{\\%}) were randomized to TAF/emtricitabine and TDF/emtricitabine, respectively. In target gene analyses, the lowest P-values for the dolutegravir and tenofovir groups were ABCG2 rs4148149 (P = 7.0x10-4) and ABCC10 rs67861980 (P = 1.0x10-2), respectively, which were not significant after correction for multiple testing. In genome-wide analyses the lowest P-values for dolutegravir, was rs7590091 in TMEM163 (P = 3.7x10-8), rs17137701 in LOC105379130 (P = 6.4x10- 8) for TAF, and rs76771105 in LOC105371716 (P = 9.7x10-8) for TDF. Conclusion: Among South African participants in a randomized clinical trial of dolutegravir plus either TAF/emtricitabine or TDF/emtricitabine, we identified several potential genetic associations with weight gain. Only TMEM163 rs7590091 withstood correction for multiple testing. These associations warrant replication in other cohorts. Corresponding Author: Phumla Sinxadi. Division of Clinical Pharmacology, Department of Medicine. K45-47 Old Main Building, Groote Schuur Hospital, Observatory, 7925, Cape Town, South Africa. Tel: +27 21 650 4096; email phumla.sinxadi@uct.ac.za Conflicts of Interests and Source of Funding: The authors declare no potential conflicts of interest related to this work. Research reported in this publication was supported by the Fogarty International Center of the National Institutes of Health (NIH) under Award Number D43 TW010559. Furthermore, this work was supported by National Research Foundation through the Thuthuka Grant [113983] and Black Academic Advancement Program grant [120647], the South African Medical Research Council (SAMRC) through self-initiated research grant (PS), the Wellcome Trust (WT) through an investigator award [212265/Z/18/Z], the National Research Foundation (NRF) of South Africa (Grant Number 119078), and core funding for the Wellcome Centre for Infectious Diseases Research in Africa [203135/Z/16/Z] (GM). Grant support included TW010559, AI110527, AI077505, TR000445 and AI110527 (DWH). Gilead Sciences and ViiV Healthcare donated study drugs for the conduct of the parent study. FV reports grants from USAID, Unitaid, SAMRC, and ViiV; personal fees and non-financial support from ViiV Healthcare and Gilead Sciences, during the conduct of the study; and personal fees from Mylan, Merck, Adcock-Ingram, Aspen, Abbott, Roche, and Johnson and Johnson, outside the submitted work. SS reports grants from USAID, Unitaid, SAMRC, and ViiV Healthcare during the conduct of the study. NC reports grants from USAID, Unitaid, SAMRC and ViiV Healthcare during the conduct of the study. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH, WT, NRF, SAMRC or other funders. Copyright {\\textcopyright} 2021 Wolters Kluwer Health, Inc. All rights reserved.},\r\nauthor = {Cindi, Zinhle and Maartens, Gary and Bradford, Yuki and Venter, Francois and Sokhela, Simiso and Chandiwana, Nomathemba and Haas, David W and Sinxadi, Phumla},\r\ndoi = {10.1097/QAI.0000000000002661},\r\nfile = {:C$\\backslash$:/Users/01462563/AppData/Local/Mendeley Ltd./Mendeley Desktop/Downloaded/Cindi et al. - 2021 - Genetic associations with weight gain among South Africans who initiated dolutegravir- and tenofovir-containing re.pdf:pdf},\r\nissn = {1525-4135},\r\njournal = {JAIDS Journal of Acquired Immune Deficiency Syndromes},\r\nkeywords = {Weight gain,dolutegravir,fund{\\_}ack,original,pharmacogenetics,tenofovir},\r\nmendeley-tags = {fund{\\_}ack,original},\r\nnumber = {3},\r\npages = {1002--1009},\r\npmid = {33625064},\r\ntitle = {{Genetic associations with weight gain among South Africans who initiated dolutegravir- and tenofovir-containing regimens}},\r\nurl = {https://journals.lww.com/jaids/Fulltext/9000/Genetic{\\_}Associations{\\_}with{\\_}Weight{\\_}Gain{\\_}among{\\_}South.95930.aspx},\r\nvolume = {87},\r\nyear = {2021}\r\n}\r\n","author_short":["Cindi, Z.","Maartens, G.","Bradford, Y.","Venter, F.","Sokhela, S.","Chandiwana, N.","Haas, D. W","Sinxadi, P."],"key":"Cindi9000","id":"Cindi9000","bibbaseid":"cindi-maartens-bradford-venter-sokhela-chandiwana-haas-sinxadi-geneticassociationswithweightgainamongsouthafricanswhoinitiateddolutegravirandtenofovircontainingregimens-2021","role":"author","urls":{"Paper":"https://journals.lww.com/jaids/Fulltext/9000/Genetic\\_Associations\\_with\\_Weight\\_Gain\\_among\\_South.95930.aspx"},"keyword":["Weight gain","dolutegravir","fund_ack","original","pharmacogenetics","tenofovir"],"metadata":{"authorlinks":{}}},"bibtype":"article","biburl":"https://drive.google.com/uc?export=download&id=1-JLqZ7RwZ3VC2d6ErLGHAtOeMRS_7GCz","dataSources":["Krmt6gt9ktB2s6ARh"],"keywords":["weight gain","dolutegravir","fund_ack","original","pharmacogenetics","tenofovir"],"search_terms":["genetic","associations","weight","gain","south","africans","initiated","dolutegravir","tenofovir","containing","regimens","cindi","maartens","bradford","venter","sokhela","chandiwana","haas","sinxadi"],"title":"Genetic associations with weight gain among South Africans who initiated dolutegravir- and tenofovir-containing regimens","year":2021}