Genetic Associations with Weight Gain among South Africans who Initiated Dolutegravir-Containing and Tenofovir-Containing Regimens
Excessive weight gain affects some HIV-positive individuals prescribed dolutegravir-containing regimens. Mechanisms underlying such weight gain are unknown. Data and DNA from antiretroviral therapy-naïve participants who were randomized to initiate dolutegravir with emtricitabine plus either tenofov...
Saved in:
Published in | Journal of acquired immune deficiency syndromes (1999) Vol. 87; no. 3; p. 1002 |
---|---|
Main Authors | , , , , , , , |
Format | Journal Article |
Language | English |
Published |
United States
01.07.2021
|
Subjects | |
Online Access | Get more information |
Cover
Loading…
Abstract | Excessive weight gain affects some HIV-positive individuals prescribed dolutegravir-containing regimens. Mechanisms underlying such weight gain are unknown.
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.
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.
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 = 7.0 × 10-4) and ABCC10 rs67861980 (P = 1.0 × 10-2), respectively, which were not significant after correction for multiple testing. In genome-wide analyses, the lowest P-values were rs7590091 in TMEM163 (P = 3.7 × 10-8) for dolutegravir, rs17137701 in LOC105379130 (P = 6.4 × 10-8) for TAF, and rs76771105 in LOC105371716 (P = 9.7 × 10-8) for TDF.
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. |
---|---|
AbstractList | Excessive weight gain affects some HIV-positive individuals prescribed dolutegravir-containing regimens. Mechanisms underlying such weight gain are unknown.
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.
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.
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 = 7.0 × 10-4) and ABCC10 rs67861980 (P = 1.0 × 10-2), respectively, which were not significant after correction for multiple testing. In genome-wide analyses, the lowest P-values were rs7590091 in TMEM163 (P = 3.7 × 10-8) for dolutegravir, rs17137701 in LOC105379130 (P = 6.4 × 10-8) for TAF, and rs76771105 in LOC105371716 (P = 9.7 × 10-8) for TDF.
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. |
Author | Maartens, Gary Venter, Willem D F Chandiwana, Nomathemba C Haas, David W Sinxadi, Phumla Sokhela, Simiso Cindi, Zinhle Bradford, Yuki |
Author_xml | – sequence: 1 givenname: Zinhle surname: Cindi fullname: Cindi, Zinhle organization: Division of Clinical Pharmacology, Department of Medicine, University of Cape Town, Cape Town, South Africa – sequence: 2 givenname: Gary surname: Maartens fullname: Maartens, Gary organization: Wellcome Centre for Infectious Diseases Research in Africa, Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Cape Town, South Africa – sequence: 3 givenname: Yuki surname: Bradford fullname: Bradford, Yuki organization: Department of Genetics, University of Pennsylvania, Philadelphia, PA – sequence: 4 givenname: Willem D F surname: Venter fullname: Venter, Willem D F organization: Ezintsha, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa – sequence: 5 givenname: Simiso surname: Sokhela fullname: Sokhela, Simiso organization: Ezintsha, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa – sequence: 6 givenname: Nomathemba C surname: Chandiwana fullname: Chandiwana, Nomathemba C organization: Ezintsha, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa – sequence: 7 givenname: David W surname: Haas fullname: Haas, David W organization: Department of Internal Medicine, Meharry Medical College, Nashville, TN – sequence: 8 givenname: Phumla surname: Sinxadi fullname: Sinxadi, Phumla organization: Division of Clinical Pharmacology, Department of Medicine, University of Cape Town, Cape Town, South Africa |
BackLink | https://www.ncbi.nlm.nih.gov/pubmed/33625064$$D View this record in MEDLINE/PubMed |
BookMark | eNpdkMtKxDAYhYMozkXfQCQv0DG3ps2yjE4tDIg64nJI06SNTJOhyShufXIrKohnc-A_5_sXZwaOnXcagAuMFhiJ7Oq-qBbojwjn-AhMsWAsyfKcTcAshBeEMGdMnIIJpZykiLMp-Ci109EqWITglZXRehfgm40dfNa27SIspXVQ9t618NEfxnthBqvkV6vzsHI2jpRu4LXfHaJuB_lqh2TpXRw5O0LSNXCjnTf-X_CgW9trF87AiZG7oM9_fA6eVjeb5W2yviurZbFOFCM8T0SdYUOZaoyQhiKCkGSEiJqpHDdYYaJNrVKJJaO0VhnJUcqpyinN0ixVXJA5uPz-uz_UvW62-8H2cnjf_o5BPgFV3WPs |
CitedBy_id | crossref_primary_10_1371_journal_pgph_0000124 crossref_primary_10_1097_QAI_0000000000003273 crossref_primary_10_1016_j_bjid_2023_102807 crossref_primary_10_1089_aid_2021_0213 crossref_primary_10_1093_ofid_ofae007 |
ContentType | Journal Article |
Copyright | Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved. |
Copyright_xml | – notice: Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved. |
DBID | CGR CUY CVF ECM EIF NPM |
DOI | 10.1097/QAI.0000000000002661 |
DatabaseName | Medline MEDLINE MEDLINE (Ovid) MEDLINE MEDLINE PubMed |
DatabaseTitle | MEDLINE Medline Complete MEDLINE with Full Text PubMed MEDLINE (Ovid) |
DatabaseTitleList | MEDLINE |
Database_xml | – sequence: 1 dbid: NPM name: PubMed url: https://proxy.k.utb.cz/login?url=http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed sourceTypes: Index Database – sequence: 2 dbid: EIF name: MEDLINE url: https://proxy.k.utb.cz/login?url=https://www.webofscience.com/wos/medline/basic-search sourceTypes: Index Database |
DeliveryMethod | no_fulltext_linktorsrc |
Discipline | Medicine |
EISSN | 1944-7884 |
ExternalDocumentID | 33625064 |
Genre | Research Support, Non-U.S. Gov't Journal Article Research Support, N.I.H., Extramural |
GeographicLocations | South Africa |
GeographicLocations_xml | – name: South Africa |
GrantInformation_xml | – fundername: Wellcome Trust – fundername: FIC NIH HHS grantid: D43 TW010559 – fundername: NCATS NIH HHS grantid: UL1 TR000445 – fundername: NIAID NIH HHS grantid: R01 AI077505 – fundername: Wellcome Trust grantid: 212265/Z/18/Z – fundername: NIAID NIH HHS grantid: P30 AI110527 – fundername: Wellcome Trust grantid: 203135/Z/16/Z – fundername: NHLBI NIH HHS grantid: UG3 HL156388 |
GroupedDBID | --- .-D .XZ .Z2 01R 0R~ 1J1 354 40H 4Q1 4Q2 4Q3 5GY 5RE 5VS 77Y 7O~ 8L- AAAAV AAAXR AAGIX AAHPQ AAIQE AAJCS AAMOA AAQKA AARTV AASCR AASOK AASXQ AAXQO ABASU ABBUW ABDIG ABIVO ABJNI ABVCZ ABXVJ ABZAD ACDDN ACEWG ACGFO ACGFS ACILI ACLDA ACOAL ACPRK ACWDW ACWRI ACXJB ACXNZ ADGGA ADHPY AE3 AE6 AEBDS AFDTB AFEXH AFRAH AFUWQ AGINI AHMBA AHOMT AHQNM AHVBC AIJEX AINUH AJIOK AJNWD AJZMW AKULP ALMA_UNASSIGNED_HOLDINGS ALMTX AMJPA AMKUR AMNEI AOHHW AWKKM BKOMP BOYCO BQLVK BYPQX C45 CGR CS3 CUY CVF DIWNM E.X EBS ECM EEVPB EIF ERAAH EX3 F2K F2L F2M F2N F5P FCALG FL- FRJ FRP GNXGY GQDEL H0~ HLJTE HZ~ IKREB IKYAY IN~ IPNFZ JK3 JK8 K8S KD2 KMI L-C NPM N~7 N~B O9- OAG OAH ODA ODMTH OHH OHYEH OLG OLH OLU OLV OLW OLY OLZ OPUJH OVD OVDNE OVIDH OVLEI OWV OWX OWY OWZ OXXIT P2P PQQKQ RIG RLZ RXW S4R S4S TAE TEORI TSPGW V2I VVN W2D W3M WOQ WOW X3V X3W XYM YOC |
ID | FETCH-LOGICAL-c4268-9b71f34cdf9af30200a4229b4c81d1c12efbc5a1a433bc7280563c8337575c692 |
IngestDate | Wed Oct 16 00:41:21 EDT 2024 |
IsDoiOpenAccess | false |
IsOpenAccess | true |
IsPeerReviewed | true |
IsScholarly | true |
Issue | 3 |
Language | English |
License | Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved. |
LinkModel | OpenURL |
MergedId | FETCHMERGED-LOGICAL-c4268-9b71f34cdf9af30200a4229b4c81d1c12efbc5a1a433bc7280563c8337575c692 |
OpenAccessLink | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8192425 |
PMID | 33625064 |
ParticipantIDs | pubmed_primary_33625064 |
PublicationCentury | 2000 |
PublicationDate | 2021-07-01 |
PublicationDateYYYYMMDD | 2021-07-01 |
PublicationDate_xml | – month: 07 year: 2021 text: 2021-07-01 day: 01 |
PublicationDecade | 2020 |
PublicationPlace | United States |
PublicationPlace_xml | – name: United States |
PublicationTitle | Journal of acquired immune deficiency syndromes (1999) |
PublicationTitleAlternate | J Acquir Immune Defic Syndr |
PublicationYear | 2021 |
SSID | ssj0016449 |
Score | 2.4242537 |
Snippet | Excessive weight gain affects some HIV-positive individuals prescribed dolutegravir-containing regimens. Mechanisms underlying such weight gain are unknown.... |
SourceID | pubmed |
SourceType | Index Database |
StartPage | 1002 |
SubjectTerms | Adult Anti-HIV Agents - administration & dosage Anti-HIV Agents - therapeutic use Drug Therapy, Combination Female Genome-Wide Association Study Heterocyclic Compounds, 3-Ring - administration & dosage Heterocyclic Compounds, 3-Ring - therapeutic use HIV Infections - drug therapy HIV-1 Humans Male Oxazines - administration & dosage Oxazines - therapeutic use Piperazines - administration & dosage Piperazines - therapeutic use Polymorphism, Genetic Prodrugs Pyridones - administration & dosage Pyridones - therapeutic use South Africa Tenofovir - administration & dosage Tenofovir - therapeutic use Weight Gain - drug effects Weight Gain - genetics |
Title | Genetic Associations with Weight Gain among South Africans who Initiated Dolutegravir-Containing and Tenofovir-Containing Regimens |
URI | https://www.ncbi.nlm.nih.gov/pubmed/33625064 |
Volume | 87 |
hasFullText | |
inHoldings | 1 |
isFullTextHit | |
isPrint | |
link | http://utb.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwnV1LT9wwELaWVkJcUN9AW-QDt1XaTeys4yOClocEEtXy6AnZxoaoJbvideix_7D_qDN-LNGyq1JyiCI7siLPF8-MPfMNIWughM9KoVRmQPdlHBRuJgWTmTalLmylhOlhvvPefn_7kO-elCedzp9W1NLtjf5kfk3NK3mKVKEN5IpZsv8h2fGg0ADPIF-4g4Th_igZI2c0Eq625jhmqx37Hc_uFvj9sZ6Qr5XXDWWB8K2LIawNNfzfaHJu4mcibcRdfZUhYVWoG-FPFga2GbrhRMc3e45lAa5n2LbKYIAxDFxj-gmmZiFRhc_yTBQJgSIKDMfWXsQGHqD745K6ufjZisrFwNNg8G-p-7hljANIsfnfb3_Uqf0IeUY9EnE3yV52N2P8ctzdKPJxJCwop7AiS84x5JG3l-yoo-u2Rz8KJXR9_vZDxRAIhw_WdwJhZbzQOmm_DuIdXXqwMFDsyOX3794Juu7UNUfmRIW1RPZx-ygea4HxKVP-phSfp33OAplPQ0x4Ot7iGbwgi1GcdD3g7iXp2OYVmd-LwRivye8IP9qGH0X40QA_ivCjHn7Uw48m-FGAHx3Dj86AHwX40Wnwowl-b8jh1y-Dje0slvTIDJiCoFq1yB3j5sxJ5Ri4Kj3Fi0JqbsBvyk1eWAerhMoVZ0wbLJ1W9pmpGBPgVpi-LN6SZ82wsUuEaitt2WOuEtJxASZWJQ2XThhl-qC09TJ5F2bvdBR4W07TvK7M7HlPFu5B-IE8d7BQ2I9gdd7oVS_Jv2srhJ0 |
link.rule.ids | 780 |
linkProvider | National Library of Medicine |
openUrl | ctx_ver=Z39.88-2004&ctx_enc=info%3Aofi%2Fenc%3AUTF-8&rfr_id=info%3Asid%2Fsummon.serialssolutions.com&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Genetic+Associations+with+Weight+Gain+among+South+Africans+who+Initiated+Dolutegravir-Containing+and+Tenofovir-Containing+Regimens&rft.jtitle=Journal+of+acquired+immune+deficiency+syndromes+%281999%29&rft.au=Cindi%2C+Zinhle&rft.au=Maartens%2C+Gary&rft.au=Bradford%2C+Yuki&rft.au=Venter%2C+Willem+D+F&rft.date=2021-07-01&rft.eissn=1944-7884&rft.volume=87&rft.issue=3&rft.spage=1002&rft_id=info:doi/10.1097%2FQAI.0000000000002661&rft_id=info%3Apmid%2F33625064&rft_id=info%3Apmid%2F33625064&rft.externalDocID=33625064 |