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Background  Individuals with two copies of the apolipoprotein-1 ( APOL1)  gene risk variants are at high risk (HR) for non-diabetic kidney disease. The presence of these risk variants is highest in West Africa, specifically in Nigeria. However, there is limited availability of dialysis and kidney transplantation in Nigeria, and most individuals will die soon after developing end-stage renal disease. Blocking the renin angiotensin aldosterone system with angiotensin-converting enzyme inhibitors (ACEi) is a well-recognized strategy to slow renal disease progression in patients with diabetes mellitus with chronic kidney disease (CKD) and in patients with HIV-associated nephropathy. We propose to determine whether presence of the  APOL1  HR genotype alters or predicts responsiveness to conventional therapy to treat or prevent CKD and if addition of an ACEi to standard combination antiretroviral therapy (ART) reduces the risk of kidney complications among non-diabetic Nigerian adults.    Methods/design  We will screen 2600 HIV-positive adults who have received ART to (1) determine the prevalence of  APOL1  risk variants and assess whether  APOL1  HR status correlates with prevalent albuminuria, estimated glomerular filtration rate (eGFR), and/or prevalent CKD; (2) assess, via a randomized, placebo-controlled trial (RCT) in a subset of these participants with microalbuminura ( n  = 280) whether addition of the ACEi, lisinopril, compared to standard of care, significantly reduces the incidence or progression of albuminuria; and (3) determine whether the  APOL1  HR genotype is associated with worse kidney outcomes (i.e. eGFR slope or regression of albuminuria) among participants in the RCT.    Conclusions  This study will examine the increasing prevalence of kidney diseases in HIV-positive adults in a West African population, and the relationship between these diseases and the  APOL1  high-risk genotype. By evaluating the addition of an ACEi to the care of individuals with HIV infection who have albuminuria, our trial will provide definitive evidence to guide strategies for management and clinical care in this population, with the goal of reducing HIV-related kidney complications.    Trial registration  ClinicalTrials.gov,  NCT03201939 . Registered on 26 August 2016.    Electronic supplementary material  The online version of this article (10.1186/s13063-019-3436-y) contains supplementary material, which is available to authorized users.

Optimal management of HIV- positive adults at risk for kidney disease in Nigeria (Renal Risk Reduction “R3” Trial): protocol and study design