Human immunodeficiency virus (HIV)-associated nephropathy (HIVAN) is the most common finding on renal biopsy in HIV-infected black patients and is also the commonest cause of end-stage renal disease in these patients. Early detection of HIVAN may be beneficial in evaluating early treatment. This study examined the pattern of renal diseases in HIV-infected South Africans and also attempted to diagnose HIVAN at an early stage. In this single-center cross-sectional study, 615 HIV-infected patients were screened for proteinuria. Thirty patients with varying degrees of proteinuria underwent renal biopsy. Patients with diabetes mellitus, uncontrolled hypertension, known causes of chronic kidney disease, and serum creatinine above 250 mumol/l were excluded. Patients in this study were not on antiretroviral therapy. HIVAN was found in 25 (83%) patients. Six of them (24%) had microalbuminuria. Altogether, seven patients with persistent microalbuminuria were biopsied and six (86%) showed HIVAN. Other biopsy findings included membranoproliferative nephropathy in two (7%) and interstitial nephritis in three (10%). Four patients with HIVAN had associated membranous nephropathy. HIVAN is the commonest biopsy finding among our study patients with HIV infection who present with varying degrees of proteinuria. Microalbuminuria is a manifestation of HIVAN in our study patients. Therefore, microalbuminuria may be an early marker of HIVAN, and screening for its presence may be beneficial. Renal biopsy may be considered in seropositive patients who present with persistent microalbuminuria, especially with low CD4 counts irrespective of good renal function. This will allow diagnosis and treatment of HIVAN at an early stage and may prevent further disease progression.