Case Presentation: A 65-year-old black woman with history of longstanding controlled HIV on highly active antiretroviral therapy (HAART) and chronic Hepatitis C co-infection, presented with a 2-day history of worsening lower back pain. She was compliant with her HAART regimen (darunavir, lamivudine, raltegravir and ritonavir) since her diagnosis in 1994, with persistently undetectable viral loads (VL) and normal CD4+ counts, the latest one of 1300cells/µL. On exam, patient was hemodynamically stable with pain localized over her left lumbar paraspinal area. Bilateral lower extremity edema was also noted. Laboratory data was significant for an elevated creatinine (10.3mg/dL) and blood urea nitrogen (83mg/dL), despite a recent baseline creatinine of 1.0mg/dL. Urine protein-to-creatinine ratio evidenced nephrotic range proteinuria of 9.05gm. Repeat HIV RNA VL was <20 copies/mL and CD4 count of 793cells/µL. A CT abdomen and pelvis showed mild diffuse enlargement of both kidneys, without significant inflammation or hydronephrosis. Her back pain was attributed to lumbar spine osteoarthritis, also seen in imaging studies. Other causes of renal failure were ruled out including anti-nuclear antibodies, anti-neutrophil cytoplasmic antibodies, cryoglobulins, antistreptolysin O, and serum/urine electrophoresis. Her kidney function continued to decline, she became oliguric and volume overloaded, ultimately requiring renal replacement therapy. Given such a dramatic declined of her renal status, a kidney biopsy was performed, which revealed collapsing focal segmental glomerulosclerosis (FSGS) and severe tubulointerstitial inflammation and injury, consistent with HIVAN. Patient tolerated well the initiation of hemodialysis, with improvement of her symptoms.

Discussion: HIVAN is the leading cause of renal failure in patients with HIV infection and is commonly seen as a late manifestation of advanced HIV or AIDS, characterized by a high VL and low T-helper cell (CD4+) count. Histology shows an aggressive form of collapsing FSGS with accompanying tubular and interstitial lesions. HIVAN is rarely present in patients with well-controlled disease and undetectable viral load. However, in these patients, AIDS usually occurred in the course of their disease, which was not our patient’s case. Although the pathogenesis is poorly understood, there is increasing evidence that renal epithelial cells can be infected by HIV and harbor replicating virus, despite undetectable VL. The mechanism of infection of renal epithelial cells, which do not express CD4+ or traditional co-receptors for HIV, remain object of ongoing research. Course of disease ranges from heavy proteinuria, followed by a reduction in the glomerular filtration rate which rapidly progresses to end stage renal disease. Therefore, prognosis is commonly poor, requiring renal replacement therapy even in those patients treated with HAART.

Conclusions: Our case demonstrates that patients who appear to be successfully treated for HIV can still develop HIVAN, despite long-term maximal viral suppression with HAART. It is essential that clinicians become aware of this complication that may occur at any stage of the disease even in the HAART era.