HIV Viremia Is Associated With APOL1 Variants and Reduced JC-Viruria

the H3Africa Kidney Disease Research Network Investigators

doi:10.3389/fmed.2021.718300

HIV Viremia Is Associated With APOL1 Variants and Reduced JC-Viruria

the H3Africa Kidney Disease Research Network Investigators

Bar-Ilan University - Azrieli Faculty of Medicine

Technion-Israel Institute of Technology
Rambam Health Care Campus Israel
University of Ghana
University of Nigeria
University of Ibadan
Kwame Nkrumah University of Science and Technology
University of Abuja, Gwagwalada
Obafemi Awolowo University
Leidos Inc
University of Kansas

Research output: Contribution to journal › Article › peer-review

3 Scopus citations

Abstract

Variants in the Apolipoprotein L1 (APOL1) gene (G1-rs60910145, rs73885319, G2-rs71785313) are common in Africans and in individuals of recent African ancestry and are associated with an increased risk of non-diabetic chronic kidney disease (CKD) and in particular of HIV associated nephropathy (HIVAN). In light of the significantly increased risk of HIVAN in carriers of two APOL1 risk alleles, a role in HIV infectivity has been postulated in the mechanism of APOL1 associated kidney disease. Herein, we aim to explore the association between HIV viremia and APOL1 genotype. In addition, we investigated interaction between BK and JC viruria, CKD and HIV viremia. A total of 199 persons living with HIV/AIDS (comprising 82 CKD cases and 117 controls) from among the participants in the ongoing Human Heredity and Health in Africa (H3Africa) Kidney Disease Research Network case control study have been recruited. The two APOL1 renal risk alleles (RRA) genotypes were associated with a higher risk of CKD (OR 12.6, 95% CI 3.89–40.8, p < 0.0001). Even a single APOL1 RRA was associated with CKD risk (OR 4.42, 95% CI 1.49–13.15, p = 0.007). The 2 APOL1 RRA genotypes were associated with an increased probability of having HIV viremia (OR 2.37 95% CI 1.0–5.63, p = 0.05). HIV viremia was associated with increased CKD risk (OR 7.45, 95% CI 1.66–33.35, P = 0.009) and with a significant reduction of JC virus urine shedding (OR 0.35, 95% CI 0.12–0.98, p = 0.046). In contrast to prior studies, JC viruria was not associated with CKD but was restricted in patients with HIV viremia, regardless of CKD status. These findings suggest a role of APOL1 variants in HIV infectivity and emphasize that JC viruria can serve as biomarker for innate immune system activation.

Original language	English
Article number	718300
Journal	Frontiers in Medicine
Volume	8
DOIs	https://doi.org/10.3389/fmed.2021.718300
State	Published - 27 Aug 2021

Bibliographical note

Publisher Copyright:
© Copyright © 2021 Kruzel-Davila, Sankofi, Kubi Amos-Abanyie, Ghansah, Nyarko, Agyemang, Awandare, Szwarcwort-Cohen, Reiner-Benaim, Hijazi, Ulasi, Raji, Boima, Osafo, May Adabayeri, Matekole, Olanrewaju, Ajayi, Mamven, Antwi, Ademola, Plange-Rhule, Arogundade, Akyaw, Winkler, Salako, Ojo, Skorecki and Adu.

Funding

Funding. This study was supported by the following grants from NIH/NHGRI/NIDD, H3Africa Kidney Disease Research Network (U54 HG006939) a Wellcome/African Academy of Sciences DELTAS Africa grant (DEL-15-007: Awandare) and World Bank ACE grant (ACE02-WACCBIP: Awandare). Supported by a grant from the Israel Science Foundation to KS (grant 3757/20) and by the Kaylie Family Foundation Kidney Disease Research Center. This project has been funded in whole or in part with federal funds from the National Cancer Institute, National Institutes of Health, under contract HHSN26120080001E. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the U.S. Government. This Research was supported [in part] by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research.

Funders	Funder number
NIDD	U54 HG006939
U.S. Government
Wellcome/African Academy of Sciences	DEL-15-007
National Institutes of Health	HHSN26120080001E
U.S. Department of Health and Human Services
National Human Genome Research Institute
National Cancer Institute
World Bank Group	ACE02-WACCBIP
Israel Science Foundation	3757/20

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

Keywords

APOL1
BK viruria
HIV viremia
JC viruria
innate immune
kidney disease

Access to Document

10.3389/fmed.2021.718300

Cite this

@article{96fa57f8361a46fda034a2b9856915a4,

title = "HIV Viremia Is Associated With APOL1 Variants and Reduced JC-Viruria",

abstract = "Variants in the Apolipoprotein L1 (APOL1) gene (G1-rs60910145, rs73885319, G2-rs71785313) are common in Africans and in individuals of recent African ancestry and are associated with an increased risk of non-diabetic chronic kidney disease (CKD) and in particular of HIV associated nephropathy (HIVAN). In light of the significantly increased risk of HIVAN in carriers of two APOL1 risk alleles, a role in HIV infectivity has been postulated in the mechanism of APOL1 associated kidney disease. Herein, we aim to explore the association between HIV viremia and APOL1 genotype. In addition, we investigated interaction between BK and JC viruria, CKD and HIV viremia. A total of 199 persons living with HIV/AIDS (comprising 82 CKD cases and 117 controls) from among the participants in the ongoing Human Heredity and Health in Africa (H3Africa) Kidney Disease Research Network case control study have been recruited. The two APOL1 renal risk alleles (RRA) genotypes were associated with a higher risk of CKD (OR 12.6, 95\% CI 3.89–40.8, p < 0.0001). Even a single APOL1 RRA was associated with CKD risk (OR 4.42, 95\% CI 1.49–13.15, p = 0.007). The 2 APOL1 RRA genotypes were associated with an increased probability of having HIV viremia (OR 2.37 95\% CI 1.0–5.63, p = 0.05). HIV viremia was associated with increased CKD risk (OR 7.45, 95\% CI 1.66–33.35, P = 0.009) and with a significant reduction of JC virus urine shedding (OR 0.35, 95\% CI 0.12–0.98, p = 0.046). In contrast to prior studies, JC viruria was not associated with CKD but was restricted in patients with HIV viremia, regardless of CKD status. These findings suggest a role of APOL1 variants in HIV infectivity and emphasize that JC viruria can serve as biomarker for innate immune system activation.",

keywords = "APOL1, BK viruria, HIV viremia, JC viruria, innate immune, kidney disease",

author = "\{the H3Africa Kidney Disease Research Network Investigators\} and Etty Kruzel-Davila and Sankofi, \{Barbara Mensah\} and \{Kubi Amos-Abanyie\}, Ernestine and Anita Ghansah and Alexander Nyarko and Seth Agyemang and Awandare, \{Gordon A.\} and Moran Szwarcwort-Cohen and Anat Reiner-Benaim and Basem Hijazi and Ifeoma Ulasi and Raji, \{Yemi Raheem\} and Vincent Boima and Charlotte Osafo and \{May Adabayeri\}, Victoria and Michael Matekole and Olanrewaju, \{Timothy O.\} and Samuel Ajayi and Manmak Mamven and Sampson Antwi and Ademola, \{Adebowale D.\} and Jacob Plange-Rhule and Fatiu Arogundade and Akyaw, \{Priscilla Abena\} and Winkler, \{Cheryl A.\} and Salako, \{Babatunde L.\} and Akinlolu Ojo and Karl Skorecki and Dwomoa Adu",

note = "Publisher Copyright: {\textcopyright} Copyright {\textcopyright} 2021 Kruzel-Davila, Sankofi, Kubi Amos-Abanyie, Ghansah, Nyarko, Agyemang, Awandare, Szwarcwort-Cohen, Reiner-Benaim, Hijazi, Ulasi, Raji, Boima, Osafo, May Adabayeri, Matekole, Olanrewaju, Ajayi, Mamven, Antwi, Ademola, Plange-Rhule, Arogundade, Akyaw, Winkler, Salako, Ojo, Skorecki and Adu.",

year = "2021",

month = aug,

day = "27",

doi = "10.3389/fmed.2021.718300",

language = "אנגלית",

volume = "8",

journal = "Frontiers in Medicine",

issn = "2296-858X",

publisher = "Frontiers Media SA",

}

TY - JOUR

T1 - HIV Viremia Is Associated With APOL1 Variants and Reduced JC-Viruria

AU - the H3Africa Kidney Disease Research Network Investigators

AU - Kruzel-Davila, Etty

AU - Sankofi, Barbara Mensah

AU - Kubi Amos-Abanyie, Ernestine

AU - Ghansah, Anita

AU - Nyarko, Alexander

AU - Agyemang, Seth

AU - Awandare, Gordon A.

AU - Szwarcwort-Cohen, Moran

AU - Reiner-Benaim, Anat

AU - Hijazi, Basem

AU - Ulasi, Ifeoma

AU - Raji, Yemi Raheem

AU - Boima, Vincent

AU - Osafo, Charlotte

AU - May Adabayeri, Victoria

AU - Matekole, Michael

AU - Olanrewaju, Timothy O.

AU - Ajayi, Samuel

AU - Mamven, Manmak

AU - Antwi, Sampson

AU - Ademola, Adebowale D.

AU - Plange-Rhule, Jacob

AU - Arogundade, Fatiu

AU - Akyaw, Priscilla Abena

AU - Winkler, Cheryl A.

AU - Salako, Babatunde L.

AU - Ojo, Akinlolu

AU - Skorecki, Karl

AU - Adu, Dwomoa

N1 - Publisher Copyright: © Copyright © 2021 Kruzel-Davila, Sankofi, Kubi Amos-Abanyie, Ghansah, Nyarko, Agyemang, Awandare, Szwarcwort-Cohen, Reiner-Benaim, Hijazi, Ulasi, Raji, Boima, Osafo, May Adabayeri, Matekole, Olanrewaju, Ajayi, Mamven, Antwi, Ademola, Plange-Rhule, Arogundade, Akyaw, Winkler, Salako, Ojo, Skorecki and Adu.

PY - 2021/8/27

Y1 - 2021/8/27

N2 - Variants in the Apolipoprotein L1 (APOL1) gene (G1-rs60910145, rs73885319, G2-rs71785313) are common in Africans and in individuals of recent African ancestry and are associated with an increased risk of non-diabetic chronic kidney disease (CKD) and in particular of HIV associated nephropathy (HIVAN). In light of the significantly increased risk of HIVAN in carriers of two APOL1 risk alleles, a role in HIV infectivity has been postulated in the mechanism of APOL1 associated kidney disease. Herein, we aim to explore the association between HIV viremia and APOL1 genotype. In addition, we investigated interaction between BK and JC viruria, CKD and HIV viremia. A total of 199 persons living with HIV/AIDS (comprising 82 CKD cases and 117 controls) from among the participants in the ongoing Human Heredity and Health in Africa (H3Africa) Kidney Disease Research Network case control study have been recruited. The two APOL1 renal risk alleles (RRA) genotypes were associated with a higher risk of CKD (OR 12.6, 95% CI 3.89–40.8, p < 0.0001). Even a single APOL1 RRA was associated with CKD risk (OR 4.42, 95% CI 1.49–13.15, p = 0.007). The 2 APOL1 RRA genotypes were associated with an increased probability of having HIV viremia (OR 2.37 95% CI 1.0–5.63, p = 0.05). HIV viremia was associated with increased CKD risk (OR 7.45, 95% CI 1.66–33.35, P = 0.009) and with a significant reduction of JC virus urine shedding (OR 0.35, 95% CI 0.12–0.98, p = 0.046). In contrast to prior studies, JC viruria was not associated with CKD but was restricted in patients with HIV viremia, regardless of CKD status. These findings suggest a role of APOL1 variants in HIV infectivity and emphasize that JC viruria can serve as biomarker for innate immune system activation.

AB - Variants in the Apolipoprotein L1 (APOL1) gene (G1-rs60910145, rs73885319, G2-rs71785313) are common in Africans and in individuals of recent African ancestry and are associated with an increased risk of non-diabetic chronic kidney disease (CKD) and in particular of HIV associated nephropathy (HIVAN). In light of the significantly increased risk of HIVAN in carriers of two APOL1 risk alleles, a role in HIV infectivity has been postulated in the mechanism of APOL1 associated kidney disease. Herein, we aim to explore the association between HIV viremia and APOL1 genotype. In addition, we investigated interaction between BK and JC viruria, CKD and HIV viremia. A total of 199 persons living with HIV/AIDS (comprising 82 CKD cases and 117 controls) from among the participants in the ongoing Human Heredity and Health in Africa (H3Africa) Kidney Disease Research Network case control study have been recruited. The two APOL1 renal risk alleles (RRA) genotypes were associated with a higher risk of CKD (OR 12.6, 95% CI 3.89–40.8, p < 0.0001). Even a single APOL1 RRA was associated with CKD risk (OR 4.42, 95% CI 1.49–13.15, p = 0.007). The 2 APOL1 RRA genotypes were associated with an increased probability of having HIV viremia (OR 2.37 95% CI 1.0–5.63, p = 0.05). HIV viremia was associated with increased CKD risk (OR 7.45, 95% CI 1.66–33.35, P = 0.009) and with a significant reduction of JC virus urine shedding (OR 0.35, 95% CI 0.12–0.98, p = 0.046). In contrast to prior studies, JC viruria was not associated with CKD but was restricted in patients with HIV viremia, regardless of CKD status. These findings suggest a role of APOL1 variants in HIV infectivity and emphasize that JC viruria can serve as biomarker for innate immune system activation.

KW - APOL1

KW - BK viruria

KW - HIV viremia

KW - JC viruria

KW - innate immune

KW - kidney disease

UR - https://www.scopus.com/pages/publications/85114743232

U2 - 10.3389/fmed.2021.718300

DO - 10.3389/fmed.2021.718300

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C2 - 34513880

AN - SCOPUS:85114743232

SN - 2296-858X

VL - 8

JO - Frontiers in Medicine

JF - Frontiers in Medicine

M1 - 718300

ER -

HIV Viremia Is Associated With APOL1 Variants and Reduced JC-Viruria

Abstract

Bibliographical note

Funding

UN SDGs

Keywords

Access to Document

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