Chronic kidney disease among HIV-positive Zambian adults with tenofovir-associated nephrotoxicity at University Teaching Hospital (UTH) in Lusaka

Abstract

Tenofovir disoproxil fumarate (TDF) is a nucleotide reverse transcriptase inhibitor (NRTI) widely used in first-line antiretroviral therapy (ART). Despite its efficacy, TDF has been associated with nephrotoxicity, particularly in patients with renal impairment. It is with this background that most countries including Zambia are replacing TDF-based regimens with Tenofovir Alafenamide (TAF). This study aimed to determine the association between TDF-induced nephrotoxicity at three months and chronic kidney disease (CKD) within five years among people living with HIV (PLWH) in Zambia. A retrospective cohort study of 182 PLWH was conducted at the Adult Center for Infectious Disease Research (AIDC) in Lusaka, Zambia. The incidence of CKD and factors associated with its development in PLWH who initiated TDF were evaluated. Kidney function trends were monitored over five years. Statistical analysis, including the Mixed-Effect model, and the Cox Proportional Hazards Regression model, were conducted to assess the relationship between early nephrotoxicity and long-term CKD. A total of 63 (34.62%) out of 182 files showed that the patients developed CKD, contributing to a total person-time of 910 person-years. The incidence rate of CKD was 69.2 cases per 1000 person-years. The findings indicated a significant association between TDF-associated nephrotoxicity and the development of CKD within five years. The mixed-effects model accounted for population-level trends and individual variability, ensuring robust results. Findings showed that removing outliers made the model more representative, with a significant decline in kidney function over time. The Cox regression model identified male sex and baseline creatinine as substantial risk factors for CKD, with good model fit and discriminatory power. Given the findings, it is recommended that regular monitoring and early intervention strategies be reinforced for patients. Furthermore, continuous evaluation of kidney function over time is crucial to effectively manage and mitigate the risks associated with CKD in PLWH.