Determinants and Incidence of Chronic Kidney Disease with Tenofovir- Based Antiretroviral Therapy Regimens: A Cohort Study in HIV-Infected Adults in South China

Abstract

Background: The data of the impact of tenofovir (TDF) on kidney damage in Chinese HIV-1 infected patients are limited.

Objective: The study aims to evaluate the incidence and risk factors of stage 3 chronic kidney disease (CKD) and rapid kidney function decline (RKFD) among Chinese HIV-1 infected patients starting with a TDF-based regimen.

Methods: We enrolled 797 TDF-initiated HIV-1-infected patients in a Chinese cohort. Kidney dysfunctions were defined as stage 3 CKD (eGFR < 60 mL/min/1.73 m² during follow-up) and RKFD (eGFR decline > 10 mL/min/1.73 m²/year). A linear mixed-effects model was used to quantify the average eGFR change per 48 weeks. A generalized estimating equation regression analysis was conducted to determine the risk factors associated with renal dysfunction. The method of multiple imputations was used to reduce the bias caused by missing data.

Results: In this retrospective study, 14 (2%) patients experienced stage 3 CKD, and 272 (34%) individuals experienced RKFD during a median of 26 (IQR, 4-78; maximum 325) weeks follow-up period. The mean loss in eGFR per 48 weeks increased consistently over time, from -2.59 mL/min/1.73 m² before 48 weeks to -17.61 mL/min/1.73 m² after 288 weeks. For every 10 mL/min/1.73 m² increase of eGFR, the risk of RKFD increased by 29% (95%CI: 18%, 40%). Each 10 years older and every 10 mL/min/1.73 m2 higher in baseline eGFR, the risk of stage 3 CKD increased to 1.56 (95% CI: 1.00, 2.43) and decreased by 65% (95% CI: 48%, 76%), respectively. Anemia and higher viral load were significantly associated with RKFD. The results were robust across a range of multiple imputation analyses.

Conclusion: TDF-associated CKD is rare in HIV-1 infected Chinese adults. Longer TDF-exposed patients are more likely to have renal dysfunction, especially those with older age, anemia, lower baseline eGFR, and higher viral load.

Keywords: HIV; antiviral therapy; chronic kidney disease; rapid kidney function decline; renal dysfunction; tenofovir.