Design and methods of the prevalence and pharmacogenomics of tenofovir nephrotoxicity in HIV-positive adults in south-western Nigeria study

Muzamil O Hassan,Akeem O Lasisi,Raquel Duarte,Saraladevi Naicker,Caroline Dickens,Victor O Mabayoje

doi:10.1186/s12882-020-02082-3

Abstract

BackgroundIndividuals of African descent are at higher risk of developing kidney disease than their European counterparts, and HIV infection is associated with increased risk of nephropathy. Despite a safe renal profile in the clinical trials, long-term use of tenofovir disoproxil fumarate (TDF) has been associated with proximal renal tubulopathy although the underlying mechanisms remain undetermined. We aim to establish the prevalence of and risk factors for TDF-induced kidney tubular dysfunction (KTD) among HIV-I and II individuals treated with TDF in south-west Nigeria. Association between TDF-induced KTD and genetic polymorphisms in renal drug transporter genes and the APOL1 (Apolipoprotein L1) gene will be examined.MethodsThis study has two phases. An initial cross-sectional study will screen 3000 individuals attending the HIV clinics in south-west Nigeria for KTD to determine the prevalence and risk factors. This will be followed by a case-control study of 400 KTD cases and 400 matched controls to evaluate single nucleotide polymorphism (SNP) associations. Data on socio-demographics, risk factors for kidney dysfunction and HIV history will be collected by questionnaire. Blood and urine samples for measurements of severity of HIV disease (CD4 count, viral load) and renal function (creatinine, eGFR, phosphate, uric acid, glucose) will also be collected. Utility of urinary retinol binding protein (RBP) and N-acetyl-beta-D-glucosaminidase (NAG) levels as surrogate markers of KTD will be evaluated. Genomic DNA will be extracted from whole blood and SNP analyses performed using the rhAMP SNP genotyping assays. Statistical analysis including univariate and multivariate logistic regression analyses will be performed to identify factors associated with KTD.DiscussionIn spite of TDF being the most commonly used antiretroviral agent and a key component of many HIV treatment regimens, it has potential detrimental effects on the kidneys. This study will establish the burden and risk factors for TDF-induced KTD in Nigerians, and explore associations between KTD and polymorphisms in renal transporter genes as well as APOL1 risk variants. This study may potentially engender an approach for prevention as well as stemming the burden of CKD in sub-Saharan Africa where GDP per capita is low and budgetary allocation for health is inadequate.

Highlights

Individuals of African descent are at higher risk of developing kidney disease than their European counterparts, and Human immunodeficiency virus (HIV) infection is associated with increased risk of nephropathy
This study may potentially engender an approach for prevention as well as stemming the burden of Chronic kidney disease (CKD) in sub-Saharan Africa where Gross domestic product (GDP) per capita is low and budgetary allocation for health is inadequate
According to UNAIDS, 42% of the new HIV infections occur among couples practicing ‘low risk’ sex, while 40% occur among high-risk populations which constitute about 1% of the general population, including female sex workers, men that have sex with men and injecting drug users [2]

Summary

Introduction

Individuals of African descent are at higher risk of developing kidney disease than their European counterparts, and HIV infection is associated with increased risk of nephropathy. According to UNAIDS, 42% of the new HIV infections occur among couples practicing ‘low risk’ sex (heterosexual), while 40% occur among high-risk populations which constitute about 1% of the general population, including female sex workers, men that have sex with men and injecting drug users [2]. Both types of the human immunodeficiency virus, type 1 and 2, are present in Nigeria; a report of the analysis of 2228 western blot results showed that 98.3% were positive for HIV-1, 0.4% were positive for HIV-2 while 0.3% were co-infections [3]. People living with HIV are at increased risk of HIV-related kidney disease, but are prone to other causes of CKD, including diabetes and hypertension, observed in the general population [9]

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