Low Incidence of Renal Dysfunction among HIV-Infected Patients on a Tenofovir-Based First Line Antiretroviral Treatment Regimen in Myanmar

Abstract

BackgroundSince 2004, Médecins Sans Frontières-Switzerland has provided treatment and care for people living with HIV in Dawei, Myanmar. Renal function is routinely monitored in patients on tenofovir (TDF)-based antiretroviral treatment (ART), and this provides an opportunity to measure incidence and risk factors for renal dysfunction.MethodsWe used routinely collected program data on all patients aged ≥15 years starting first-line TDF-based ART between January 2012 and December 2013. Creatinine clearance (CrCl) was assessed at base line and six-monthly, with renal dysfunction defined as CrCl < 50ml/min/1.73m2. We calculated incidence of renal dysfunction and used Cox regression analysis to identify associated risk factors.ResultsThere were 1391 patients, of whom 1372 had normal renal function at baseline. Of these, 86 (6.3%) developed renal dysfunction during a median time of follow-up 1.14 years with an incidence rate of 5.4 per 100 person-years: 78 had CrCl between 30–50ml/min/1.73m2 and were maintained on TDF–based ART, but 5 were changed to another regimen: 4 because of CrCl <30ml/min/1.73m2. Risk factors for renal dysfunction included age ≥45 years, diagnosed diabetes, underlying renal disease, underweight and CD4 count <200cells/mm3. There were 19 patients with baseline renal dysfunction and all continued on TDF-based ART: CrCl stayed between 30–49 ml/min/1.73m2 in five patients while the remainder regained normal renal function.ConclusionsIn a resource-poor country like Myanmar, the low incidence of renal toxicity in our patient cohort suggests that routine assessment of CrCl may not be needed and could be targeted to high risk groups if resources permit.

Renal Dysfunction during Tenofovir Use in a Regional Cohort of HIV-Infected Individuals in the Asia-Pacific

“…We found that older age (>50 years), lower pre-TDF eGFR (<60 ml/min/1.73m 2 ) and PI-based regimen are associated with higher risk of renal dysfunction in multivariate analysis, all of which were compatible with previous studies and the WHO recommendations for regular S-Cr monitoring [10,19–21,24]. The higher risk in older age and lower pre-TDF eGFR can be explained by the fact that the CKD prevalence rises with age due to the increasing prevalence of risk factors for CKD, such as diabetes and hypertension, and the natural decline of renal function associated with aging [25].…”

The effect of Tenofovir on renal function among Ugandan adults on long-term antiretroviral therapy: a cross-sectional enrolment analysis

“…Similarly, a 10 year follow-up cohort study of HIV-positive patients, reported that the quantified loss in eGFR attributable to Tenofovir was relatively modest after many years of exposure [12]. Since the majority of our patients had been on ART for more than 9 years, our failure to find an association between renal dysfunction and duration on Tenofovir containing ART can be explained by previous studies that reported that the loss in eGFR attributable to Tenofovir seemed to occur during the first years of exposure between 0.5 and 31.2 months and stabilized after that [16, 17, 25–28]. Post marketing studies reported advanced age, low body weight, comorbidities such as diabetes mellitus, hypertension, as some of the risk factors for Tenofovir induced renal dysfunction [27, 29, 30].…”

“…However, we found no differences in glomerular function between patients who were on Tenofovir containing ART and those who were on Non-Tenofovir containing ART. Other studies have similarly reported no or minimal reductions in glomerular filtration rate among patients on Tenofovir [17, 21, 25]. Similarly, a 10 year follow-up cohort study of HIV-positive patients, reported that the quantified loss in eGFR attributable to Tenofovir was relatively modest after many years of exposure [12].…”

Does the Structured Operational Research and Training Initiative (SORT IT) continue to influence health policy and/or practice?

“…In the core group meeting between national programs for VL and HIV/AIDS, consensus was made on developing clearer recommendations and convergence between WHO ART guidelines and VL guidelines. Furthermore MSF is planning to do a clinical trial in collaboration with national health authorities to generate further robust evidence for best treatment options for HIV-VL co-infected patients in India.’ Kyaw N. et al (2015), Myanmar [30]The study used routinely collected programme data on all patients aged ≥ 15 years starting first-line tenofovir-based ART between 2012 and 2013. Creatinine clearance was assessed at base line and 6 monthly and incidence of renal dysfunction was calculated.The low incidence of renal toxicity in the patient cohort suggests that routine assessment of creatinine clearance may not be needed and could be targeted to high risk groups if resources permit. ‘ The national program adopted the alternative low cost screening method (urine protein testing) for screening of renal dysfunction in patients taking tenofovir and now uses the creatinine test only in high risk patients.’ Contributed to existing evidence leading to scale up of interventions Dave P. et al (2015), India [31]This was a retrospective cohort study involving a review of electronic patient records maintained routinely under the National Tuberculosis Programme, Gujarat, India in 2013.Offering rapid drug susceptibility testing (DST) at diagnosis improved the treatment outcomes among patients with pulmonary tuberculosis. ‘ The study findings strengthened the evidence of the effect of rapid DST at diagnosis on treatment outcomes of TB patients, which reinforced the national policy and has contributed to scale up of rapid DST facilities in the country.’ Change in policy and/or practice at subnational level Shewade H. et al (2014), India [32]Mixed-methods study, quantitative component consisted of retrospective cohort study reviewing records of all presumptive MDR-TB patients between October 2012 and September 2013.…”

“…Strong evidence from a multi-centric study involving multiple stakeholders might well bring about a policy change by itself [30]. However, it is possible that, in a given context with favourable background evidence, a single study may precipitate the final decision for policy change.…”