Annual change in estimated glomerular filtration rate and predictors of rapid kidney function decline among antiretroviral therapy-experienced older people with HIV in Uganda, sub-Saharan Africa: A cohort study

Abstract Introduction : Older people with HIV (PWH) receiving antiretroviral therapy (ART) in sub-Saharan Africa are at high risk of chronic kidney disease (CKD) while routine kidney function monitoring remains limited in this setting. We examined changes in estimated glomerular filtration rate (eGFR) per year and risk of rapid kidney function decline over 3 years among older PWH in Uganda. Methods Our cohort study included 500 PWH aged ≥ 60 years receiving ART at the Infectious Diseases Institute in Uganda who were followed between 2020–2024. We measured serum creatinine at each annual visit. We estimated predictors of annual eGFR change and rapid kidney function decline (defined as eGFR loss ≥5mL/min/1.73m 2 /year) in linear mixed effects and modified Poisson regression models, respectively. Results Among 500 PWH with a median age of 64 (interquartile range (IQR): 62,68) years, 49% were female, and their median eGFR was 75 (IQR: 60,92) mL/min/1.73m 2 at baseline. Over a median follow up of 2.95 years, the cohort experienced a -0.7 (IQR: -3.3,4.7) mL/min/1.73m 2 change in eGFR per year, and 76 (15.2%) participants developed rapid kidney function decline. Female sex (1.82 [95%CI:0.95–2.70]), use of integrase strand transfer inhibitors (2.50[95%CI:1.52–3.48]), higher CD4 cell count (0.21[95%CI:0.04–0.37]), and hepatitis B surface antigen positivity (4.19[95%CI:2.11–6.27]) at baseline were associated with improvement in eGFR (mL/min/1.73m 2 ) per year. Longer cumulative exposure to tenofovir disoproxil fumarate (TDF) (relative risk (RR) = 1.33 (95%CI:1.11–1.60) per doubling of TDF exposure in years), and male sex (RR = 1.91 (95%CI:1.08–3.37)) were associated with a higher risk of rapid kidney function decline. A higher CD4 cell count (RR = 0.91 per 100 cells increase/ml; 95% CI: 0.84–0.99)) and use of integrase strand transfer inhibitors (RR = 0.41; 95%CI: 0.23–0.72) were associated with a reduced risk of rapid kidney function decline. Switching from TDF prior to or during the cohort did not mitigate the risk of rapid kidney function decline. Conclusions Among older PWH in sub-Saharan Africa, annual eGFR decline was mild overall and comparable to other aging populations. However, a subset of this population experienced rapid kidney function decline especially if they were males and those exposed to TDF, and these may need tailored or more frequent kidney function monitoring.