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Renal disease is increasingly being reported in human immunodeficiency virus (HIV)-infected children with or without antiretroviral drugs. This study was aimed at determining the prevalence of renal disease in HIV-infected children with or without treatment in Calabar, Nigeria. A descriptive cross-sectional study of 146 consecutive HIV-infected children seen at the pediatric HIV clinic of General Hospital Calabar and University of Calabar Teaching Hospital, aged six weeks to 15 years, was carried out from February 1 to September 30, 2015. Demographic and clinical data were obtained by interviewing parents and from medical records of each subject. Clinical examination, anthropometry (weight and height), and blood pressure were done on each child. Each child’s urine was tested for persistent proteinuria using combi-10-urinalysis strips. All negative urine samples had urine albumin and urine creatinine determined using immunoturbidimetric assay and Jaffe kinetic reaction, respectively; hence, the urine albumin and urine creatinine ratio was calculated. The serum creatinine of each subject was estimated and used to calculate estimated glomerular filtration rate (eGFR) using Schwartz formula. Renal disease was defined by persistent proteinuria >+1 on dipstick or urine protein–creatinine ratio >0.2, decreased eGFR 30–300 mg/g). Data were analyzed using IBM SSPS Statistics version 20.0, and P ≤0.05 was statistically significant. A total of 146 children were recruited. Eighty-five (58.2%) were male and 61 (41.8%) were female giving a male:female ratio of 1:0.7. Fifty-three (36.3%) had renal disease, 48 (32.9%) had microalbuminuria, and five (3.4%) had persistent proteinuria. There was no significant association between renal disease and severe HIV disease (P >0.05), highly active antiretroviral therapy treatment (P >0.05), and duration of treatment (P >0.05). Renal disease is common in HIV-infected children with or without medication. Hence, they should be screened for renal disease at diagnosis and periodically.