Association Between Long term Tenofovir-Based therapy and the Incidence of Renal Dysfunction in Adult HIV-Positive Patients at Ronald Ross Hospital: A Retrospective Cohort Study
Date
2016
Authors
Wantakisha, Enock W.R.
Journal Title
Journal ISSN
Volume Title
Publisher
University of Zambia
Abstract
Tenofovir disoproxil fumerate (TDF)-based antiretroviral therapy
places HIV-infected patients at high risk of renal dysfunction. Therefore, we evaluated if the
incidence of renal dysfunction in HIV positive adults patients on long term tenofovir-based
regimen versus those on non-tenofovir use.
We performed a retrospective cohort analysis of 834 HIV positive patients at the
counselling and testing center (CTC) at Ronald Ross General Hospital. Patients were
evaluated at baseline and with every follow up visit for creatinine and creatinine clearance
(Cockcroft-Gault formula) calculated. Patients’ records in data management software called
SMARTCARE from 2008 to 2014 were reviewed to compare renal function between patients
on TDF-containing regimen (447 patients) with non-TDF containing regimen (387 patients).
We evaluated Glomerular Filtration Rate (GFR) using creatinine clearance as defined by the
Kidney Disease Outcomes Quality Initiative Classification (K/DOQI) by GFR.The effect of
creatinine, urea and exposure to TB medication, Cotrimoxazole use and CD4 cell count on
GFR were also follow up for 18 months. Univariate and Multivariate logistic regression was
used to determine the factors associated with renal dysfunction. We report multivariable
hazard ratios (Cox modeling) and binary outcomes with predictors retained if P < 0.05 and
analyzed survival time. Renal function was categorized as CrCl <50 ml/min and ≥ 50 ml/min.
Potential predictor variables for renal dysfunction included in the multivariable models were
age, sex, weight, creatinine and treatment with tenofovir.
The CD4 cell count, urea, anti-TB medication, Cotrimoxazole use, education level,
employment status and creatinine clearance were similar at baseline between the two groups.
There was no significant difference from exposure to TDF between groups on renal
dysfunction development (OR: 2.52, 95% CI, 0.79-8.0, P-value=0.118) as a predictor of renal
dysfunction in both univariate and multivariate analysis. Creatinine and creatinine clearance
between groups at baseline and 18 months were not statistically different. The prevalence of
mild and severe renal dysfunction among HIV-positive adults on TDF-based therapy was
18.4% and 0.2% respectively at 18 months during therapy. Those patients on TDF who were
older than 50 years and presented with CrCl <50 ml/min and a CD4 cell count below 500
cells/uL at baseline were more likely to develop renal dysfunction. Twenty-four (5.5%) and 2
(0.5%) patients presented with mild and severe renal dysfunction respectively at baseline.
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Further, Univariate and multivariate analysis showed that ages <49 years than >50 (AOR:
6.35 (2.18-18.4), p-value=0.001), and higher CD4+ cell count >500 cells/uL (AOR: 1.24
(0.97-1.07), P-value=0.051) were less likely associated with renal dysfunction. Age per yearincrease
(OR: 6.35, 95% CI -2.18-18.4, P<0.001) and CD4 cell count per 1 cell-increase/μl
(OR: 3.03, 95% CI, 0.98-9.28, P=0.053) on univariate were important factors affecting renal
dysfunction.
We found no evidence to suggest that TDF-based therapy is associated with
decline in renal function and that it does not affect creatinine clearance. However, there is
need for close renal monitoring of patients initiated on TDF by using creatinine clearance.
Description
Masters in Epidemiology
Keywords
AIDS (Disease)--Chemotherapy--Zambia , Antiretroviral agents.