Genetic Determinants of Kidney Disease in People of African Ancestry With HIV (GEN-AFRICA)

Genetic and Clinical Determinants of Cardiovascular Disease, Diabetes, Kidney Disease and Obesity in People of African Ancestry With HIV

Black ethnicity is a major risk factor for chronic kidney disease [CKD] in people with HIV infection, suggesting that genetic factors are an important determinant of kidney disease progression in this population. The Gen-Africa study was established in 2018 to allow the study of genetic and clinical risk factors for CKD in people with HIV in the UK. Just over 3000 people across 15 sites were enrolled between May 2018 and January 2020. Demographic and clinical information was collected, and biological samples (buffy coats, plasma and urine) obtained. Cross-sectional analyses have revealed that participants of West-African ancestry are at higher risk of CKD and end-stage kidney disease [ESKD], and that genetic variants in the apolipoprotein L1 (APOL1) gene and sickle cell trait (SCT) are predictors of CKD and ESKD. The pathogenesis of APOL1- and SCT-associated CKD is incompletely understood, and additional, longitudinal data will be collected to improve understanding of the contribution of demographic, traditional CKD (diabetes, hypertension, obesity/metabolic syndrome, cardiovascular disease) and HIV (immuno-virological and hepatitis B/C co-infection status, antiretroviral medications) risk factors as well as additional genetic and epigenetic markers.

Study Overview

• Status: Active, not recruiting
• Conditions: Cardiovascular Diseases; Kidney Diseases; Obesity; Diabetes Mellitus; Genetic Predisposition to Disease; Kidney Injury; HIV Nephropathy

Detailed Description

At enrolment, just over 3,000 people of (self-identified) back ethnicity provided informed consent, a blood and urine sample, weight, height, and blood pressure measurements, and completed a short questionnaire about your health issues and lifestyle factors. HIV treatment history, including most recent and nadir CD4 count and HIV viral load, viral hepatitis status and kidney function measurements were recorded. Records for about 2,350 participants have been successfully linked to the United Kingdom Collaborative HIV Cohort (UK CHIC) which has collected data (demographics, clinical and laboratory parameters) on people with HIV since 1998 at selected clinics in the United Kingdom.

Several GEN-AFRICA sub-studies (CKD-AFRICA, Coronavirus disease (CoV)-AFRICA, Ob-AFRICA) have been conducted or are being planned. Each of these studies has received, or will be submitted for, regulatory approval. The studies have allowed or will allow collection of more detailed clinical information, additional biological samples, and/or through linkage with electronic clinical records, collection of longitudinal data on HIV (CD4, HIV viral load, AIDS-defining illnesses, and details of antiretroviral therapy), comorbidities (diabetes, hypertension, kidney disease, cardiovascular events), measurements such as blood pressure and weight, and results of blood tests including measures of kidney function performed as part of clinical monitoring.

Data collected as part of the GEN-AFRICA study / sub-studies are stored at King's College Hospital under their GEN-AFRICA/CKD-AFRICA/CoV-AFRICA/Ob-AFRICA study identifiers (ID). Samples collected as part of these protocols are labeled by study ID and stored in the James Black Building, King's College London, London, UK, in compliance with human tissue act (HTA) standards. Prof. Frank post is the custodian of the data and samples and will be responsible for ensuring all study activity is compliant with relevant data protection and other policies.

• Study Type: Observational
• Enrollment (Actual): 3029

Contacts and Locations

Study Locations

• United Kingdom
  • London, United Kingdom, SE5 9RJ
    • King's College Hospital NHS Foundation Trust

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: N/A

• Sampling Method: Non-Probability Sample

Study Population

Black people with HIV infection who received care at one of 15 HIV clinics in the United Kingdom.

Description

Inclusion Criteria:

• HIV positive
• Black ethnicity (self-identified)
• Informed consent

Exclusion Criteria:

• None

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Other

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Kidney disease	Incidence and predictors of end-stage kidney disease, chronic kidney disease, HIVAN, focal and segmental glomerulosclerosis (FSGS), tenofovir disoproxil fumarate (TDF)-associated kidney injury.	2018-2030

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Coronavirus disease (COVID-19)	Incidence and clinical and genetic determinants of COVID-19	2020-2023
Multi-morbidity	Clinical and social determinants of multi-morbidity	2019-2023
Weight change	Weight change in relation to antiretroviral exposures	2013-2024
Obesity	Incidence of obesity in relation to antiretroviral exposures	2013-2024
Dysglycaemia	Relationship between fasting blood glucose/HbA1c and waist circumference/BMI	2019-2023
Insulin resistance	Relationship between fasting blood glucose/HbA1c, insulin/C-peptide, and waist circumference/BMI	2019-2023

Collaborators and Investigators

• Sponsor: King's College Hospital NHS Trust
• Collaborators: University of Pennsylvania; Gilead Sciences; The Leeds Teaching Hospitals NHS Trust; Medical Research Council; Vanderbilt University; Guy's and St Thomas' NHS Foundation Trust; Barts & The London NHS Trust; Royal Free Hospital NHS Foundation Trust; Manchester University NHS Foundation Trust; Chelsea and Westminster NHS Foundation Trust; University of Cape Town; Brighton and Sussex University Hospitals NHS Trust; Newcastle-upon-Tyne Hospitals NHS Trust; North Middlesex University Hospital NHS Trust; Imperial College Healthcare NHS Trust; St George's University Hospitals NHS Foundation Trust; Lewisham and Greenwich NHS Trust; South Tees Hospitals NHS Foundation Trust; Central and North West London NHS Foundation Trust; Africa Advocacy Foundation; Guy's and St. Thomas' Charity; British HIV Association
• Investigators: Principal Investigator: Frank A Post, King's College Hospital NHS Trust

Publications and helpful links

General Publications

• Hung RKY, Santana-Suarez B, Binns-Roemer E, Campbell L, Bramham K, Hamzah L, Fox J, Burns JE, Clarke A, Vincent R, Jones R, Price DA, Onyango D, Harber M, Hilton R, Booth JW, Sabin CA, Winkler CA, Post FA; GEN-AFRICA study group. The epidemiology of kidney disease in people of African ancestry with HIV in the UK. EClinicalMedicine. 2021 Jul 8;38:101006. doi: 10.1016/j.eclinm.2021.101006. eCollection 2021 Aug.
• Hung RKY, Binns-Roemer E, Booth JW, Hilton R, Harber M, Santana-Suarez B, Campbell L, Fox J, Ustianowski A, Cosgrove C, Burns JE, Clarke A, Price DA, Chadwick D, Onyango D, Hamzah L, Bramham K, Sabin CA, Winkler CA, Post FA; GEN-AFRICA Study Group. Genetic Variants of APOL1 Are Major Determinants of Kidney Failure in People of African Ancestry With HIV. Kidney Int Rep. 2022 Jan 25;7(4):786-796. doi: 10.1016/j.ekir.2022.01.1054. eCollection 2022 Apr.
• Hung RKY, Binns-Roemer E, Booth JW, Hilton R, Fox J, Burns F, Harber M, Ustianowski A, Hamzah L, Burns JE, Clarke A, Price DA, Kegg S, Onyango D, Santana-Suarez B, Campbell L, Bramham K, Sharpe CC, Sabin CA, Winkler CA, Post FA; GEN-AFRICA Study Group. Sickle Cell Trait and Kidney Disease in People of African Ancestry With HIV. Kidney Int Rep. 2021 Dec 13;7(3):465-473. doi: 10.1016/j.ekir.2021.12.007. eCollection 2022 Mar.
• Hung RKY, Rosenberg KL, David V, Binns-Roemer E, Booth JW, Hilton R, Fox J, Burns F, Ustianowski A, Cosgrove C, Hamzah L, Burns JE, Clarke A, Chadwick D, Price DA, Kegg S, Campbell L, Bramham K, Sabin CA, Post FA, Winkler CA; GEN-AFRICA Study Group. GSTM1 Copy Number and Kidney Disease in People With HIV. Kidney Int Rep. 2022 May 13;7(8):1901-1904. doi: 10.1016/j.ekir.2022.05.003. eCollection 2022 Aug. No abstract available.
• Hung R, Patel N, Fox J, Cosgrove C, Pett SL, Burns F, Ustianowski A, Rosenvinge M, Bhagani S, Dusheiko G, Childs K, Post FA; GEN-AFRICA study group. Prevalence of HIV/hepatitis B and HIV/hepatitis C coinfection among people of East, South, Central and West African ancestry in the United Kingdom. AIDS. 2021 Aug 1;35(10):1701-1704. doi: 10.1097/QAD.0000000000002929.
• Mazaheri T, Buchanan D, Hung R, Campbell L, Hamzah L, Bramham K, Vincent RP, Post FA. Creatinine and cystatin C-based estimated glomerular filtration rate estimates of kidney function in Black people with HIV on antiretroviral therapy. AIDS. 2023 Apr 1;37(5):753-758. doi: 10.1097/QAD.0000000000003466. Epub 2022 Dec 23.
• Cechin L, Campbell L, Oliveira A, Goff LM, Post FA. HbA1c screening for diabetes mellitus and to evaluate diabetic control in people of African ancestry with HIV in South London. Int J STD AIDS. 2023 Jun;34(7):484-487. doi: 10.1177/09564624231162163. Epub 2023 Mar 15.

Study record dates

Study Major Dates

• Study Start (Actual): May 1, 2018
• Primary Completion (Actual): January 31, 2020
• Study Completion (Estimated): January 31, 2030

Study Registration Dates

• First Submitted: January 3, 2023
• First Submitted That Met QC Criteria: January 5, 2023
• First Posted (Actual): January 17, 2023

Study Record Updates

• Last Update Posted (Actual): October 23, 2023
• Last Update Submitted That Met QC Criteria: October 20, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Urologic Diseases; Disease Attributes; Overnutrition; Nutrition Disorders; Overweight; Body Weight; Disease Susceptibility; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Cardiovascular Diseases; Kidney Diseases; Obesity; Genetic Predisposition to Disease
• Other Study ID Numbers: 239895

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: The database contains personal and sensitive information and is therefore not publicly available. Access to the study data and/or samples is governed by the National Health Service data access policy and those of King's College Hospital National Health System (NHS) Foundation Trust, the study sponsor. The Gen-AFRICA cohort is open to collaborations, and all requests from researchers who meet the criteria for access to fully anonymized patient level data will be considered.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No