Urinary Cytology Associated With Human Polyomavirus and Indinavir Therapy in HIV-Infected Patients

We retrospectively analyzed 155 urine cytology samples (78 from patients treated with indinavir; 77, no indinavir) from 90 HIV+ patients to evaluate possible association between human polyomavirus and hematuria and to describe indinavir-associated urinary cytologic findings. The CD4 count also was recorded. Variables studied included the presence of cellular viral changes consistent with polyomavirus infection (PVCs), microscopic hematuria, multinucleated cells, indinavir crystals, neutrophils, and eosinophils. Twenty-two samples (15.8%) from patients with CD4 counts of more than 200/µL (>200 × 10 6 /L) showed PVCs. Multinucleated cells, of presumed histiocytic origin based on morphologic features and selective immunocytochemical findings, were present in a higher percentage of samples from indinavir-treated patients. Neutrophils were present in a higher percentage of indinavir-treated patients. Indinavir crystals were identified in 9 samples (12%) from patients receiving indinavir. The lower percentage of PVCs in HIV+ patients with high CD4 counts likely represents an indirect antipolyomavirus indinavir effect by boosting immunity. Multinucleated cells (presumably histiocytic) and acute inflammation are associated with indinavir therapy. Indinavir crystals have a characteristic fan or circular lamellate appearance. Because indinavir crystals may be associated with genitourinary disease, recognizing and reporting them is clinically relevant in HIV+ patients. Genitourinary disease will develop in one third of HIV+ patients or those with AIDS, 1 with hematuria reported in more than 25%. 2 The cause of hematuria in immunocompromised patients may be related to infection with or reactivation of the human polyomavirus (PV), based on the previously reported association of the BK virus (BKV) with hemorrhagic cystitis in an HIV+ patient and in bone marrow transplant recipients 3-5 and microscopic hematuria following bone marrow transplantation. 6 Protease inhibitors are used commonly for the treatment of HIV+ patients. During treatment with one such drug, indinavir, cystitis and pyuria have developed. We have observed the presence of indinavir crystals and multinucleated cells morphologically suggestive of a histiocytic origin in urine samples from patients receiving indinavir therapy. During the last several years, routine urinary cytologic studies in HIV+ patients for the evaluation of microscopic hematuria, crystals, pyuria, drug reaction, and cystitis have been done in our laboratory. We performed a retrospective study on these samples to evaluate the presence of PV cells and its possible association with hematuria and to analyze the cytologic features associated with indinavir therapy.