Genetic Determinants of Kidney Disease in People of African Ancestry With HIV

Obesity Clinical Trial

— GEN-AFRICA  

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT05685810
• Other study ID #: 239895
• Status: Active, not recruiting
• Start date: May 1, 2018
• Est. completion date: January 31, 2030

Study information

• Verified date: October 2023
• Source: King's College Hospital NHS Trust
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational [Patient Registry]

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 3029
• Est. completion date: January 31, 2030
• Est. primary completion date: January 31, 2020
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• HIV positive

• Black ethnicity (self-identified)

• Informed consent

Exclusion Criteria:

• None

Related Conditions & MeSH terms

• Cardiovascular Diseases
• Diabetes Mellitus
• Genetic Predisposition to Disease
• Kidney Diseases
• Kidney Injury
• Obesity

Locations

Country	Name	City	State
United Kingdom	King's College Hospital NHS Foundation Trust	London

Sponsors (23)

Lead Sponsor

Collaborator

King's College Hospital NHS Trust

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

Country where clinical trial is conducted

United Kingdom, 

References & Publications (7)

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 — View Citation

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 Wes — View Citation

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. Si — View Citation

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. Geneti — View Citation

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 — View Citation

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 kidne — View Citation

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 — View Citation

Outcome

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