Substituting tenofovir for stavudine in resource-limited settings: there are challenges ahead

Abstract

We read with interest the opinion paper by Calmy et al. [1] about the need to link science and clinical practice in scaling-up antiretroviral therapy (ART) in resource-limited settings. We would like to highlight an important topic that was not addressed in this study. Although there is now a general commitment to move away from stavudine-based ART towards less-toxic combinations, particularly tenofovir, the vast majority of the more then three million individuals in low and middle-income countries today still take stavudine-containing regimens [2]. As these will not be substituted overnight, a high number of patients will remain exposed to the long-term toxicity of stavudine within the years to come. Therefore, there remains a need to develop evidence-based guidelines how to manage these toxicities at all levels of the healthcare system. When aiming for the routine substitution of stavudine, it should be considered that most patients will have been on ART for a long period and therefore may be at risk for treatment failure. Given the limited access to viral load testing, treatment failure may not have been detected [3]. Substituting tenofovir for stavudine in a person on a failing ART regimen will induce resistance to tenofovir. Therefore, before considering a substitution from stavudine to tenofovir, a rigorous assessment of the efficacy of the ART regimen should be performed, ideally with viral load testing. In case treatment failure is suspected, switching to tenofovir with a protease inhibitor-containing regimen should be considered. Moreover, switching from stavudine to tenofovir in a failing first-line regimen may not be ideal because stavudine may induce the K65R mutation (causing resistance to tenofovir), particularly in patients with a non-subtype B HIV infection [4]. Finally, a recent study [5] from Zambia demonstrated that nephropathy occurs frequently in patients accessing ART programs, and is associated with increased mortality while on ART. Particularly in the absence of the possibility to evaluate renal function, renal toxicity caused by tenofovir could become a new problem for ART roll out programs [6]. Certainly, also in countries with limited resources, there is an urgent need to set up pharmacovigilance programs. Acknowledgements J.V.G. prepared the first draft. L.L. and R.C. contributed to the intellectual content and the writing of the final text. All authors read and approved the final text.