Prevalence and factors associated with renal dysfunction in patients on tenofovir disoproxil fumarate-based antiretroviral regimens for HIV infection in Southern India

Abstract

Objectives: Tenofovir disoproxil fumarate (TDF) is a nucleotide reverse transcriptase inhibitor commonly used in the treatment of HIV infection. This retrospective study aims to establish the prevalence of abnormal renal function among patients with HIV receiving TDF, and to investigate the risks for TDF-related renal dysfunction in this population. Methods: Patients at the YRGCARE Medical Centre, Voluntary Health Services, receiving TDF-containing antiretroviral (ART) regimens between January 2002 and March 2017, were assessed for renal dysfunction using creatinine level and eGFR (DAIDS/NIH) during continuum of care. Demographic data and comorbidities were analysed for association with TDF toxicity. Data were obtained from the Natural History Study Database. Other causes of renal dysfunction were excluded. Results: From the 14,118 patients on ART between 2002 and 2017 seen in the clinic, 7171 (50.8%) were initiated on TDF-containing regimens. Among these, 4400 were on a first-line NNRTI regimen, and 2771 on a second-line PI/r regimen, initiated after failure of first-line therapy. The majority of patients on ART were male, with a median age for the whole sample of 36 years (IQR 30–42). At ART initiation, the median CD4 cell count was 277 cells/mm3 (IQR 165–421) and the viral load (VL) 31,198 HIV-1 copies/mL (IQR 400–226,690). Median duration of follow-up was 5.1 years (IQR 2.3–9.5). The prevalence of renal dysfunction in patients taking TDF was 5.6%. Increased age, low BMI, low baseline CD4 cell count, hypertension and diabetes were associated with tenofovir toxicity (P>0.05). Concomitant PI use was not associated with increased risk for renal dysfunction (P>0.05). Conclusions: The prevalence of renal dysfunction associated with TDF in our study population was higher than in other well-resourced settings, suggesting the need for increased renal parameter monitoring in patients in resource-limited settings. Treatment with ART should be initiated earlier and BMI should be maintained ≥18.5 kg/m2 through adequate nutrition and prevention of opportunistic infections. For patients with multiple comorbidities, tenofovir alafenamide (TAF) should be considered, instead of TDF, to avoid renal dysfunction.

Keywords

• HIV, tenofovir disoproxil fumarate, toxicity, resource-limited settings, TAF, India