The epidemiology of Tenofovir-associated renal failure in patients on antiretroviral therapy in Swaziland

Abstract

Background: Tenofovir (TDF) forms part of the backbone of first and second line HIV infection management. There is limited data from resource-constrained settings on nephrotoxic adverse effects of Tenofovir based antiretroviral therapy (ART). Objective: We investigated the incidence and risk factors of TDF-associated nephrotoxicity in a cohort of HIV-infected patients on either TDF or Zidovudine (AZT) based first line ART. Methods: A retrospective analysis was conducted on a sample of participants initiated on first-line TDF- and Zidovudine (AZT)-based regimens between January 2010 and December 2015; from the national ART electronic database of Mbabane Government and Raleigh Fitkins Memorial hospitals in Swaziland. Time-to-onset of toxicity was assessed using Kaplan-Meier survival analysis and the log rank test was used to compare renal dysfunction by TDF or AZT first line regimen status. Toxicity incidence rate was calculated and multivariate Cox regression model was used to identify the potential risk factors. Main Findings: A total of 1,119 participants with median age 36 years (IQR: 18 to 79 years), were included in the analysis 83% (n=929) on TDF and 17% on AZT (n=190). The median time to onset of toxicity was 6.72 months (IQR: 0.03 to 81.61). The overall incidence rate was 8.08 per 1000 person-months. TDF-associated nephrotoxicity was 9.44 per 1000 person-months (95% CI: 7.79 to 11.44) and 4.83 per 1000 person-months (95% CI: 3.18 to 7.33) for AZT. Participants on TDF-based regimen were more likely to develop toxicity in comparison to AZT, hazard ratio 2.08 (95% CI: 1.27 to 3.40, p=0.003). The mean CD4 count was 194 cells/_L (95% CI: 207.61 to 228.75), and mean eGFR was 123.56, (95% CI: 121.22 to 125.92). The co-variates: sex, age, WHO clinical staging, body mass index and CD4 cell count were not associated with developing nephrotoxicity (p>0.05). Conclusion: Although TDF is effective in HIV management, it is associated with a two-fold increased risk of abnormal renal function during the follow-up period compared to those on AZT. This underlines the paramount importance of regular record-keeping for thorough pharmacovigilance and routine surveillance due to its wide usage.