Objective: The objective of this study was to analyze human immunodeficiency virus (HIV) dynamics across the blood-retinal barrier and to determine whether the high levels of HIV in the eye are associated with any ocular disorders in HIV-infected patients. Design: This study included a prospective case series of 40 HIV-positive patients with uveitis. INTERVENTION:: Clinical and laboratory examinations included plasma and intraocular HIV-1 RNA loads as well as the clinical manifestations of uveitis. Results: Intraocular HIV-1 RNA was detected in 32% (13/40) of HIV-positive patients with uveitis. Intraocular HIV-1 RNA loads were associated with high HIV-1 RNA plasma loads (P < 0.001) and not being on HAART therapy (P = 0.005). In addition, detectable intraocular HIV-1 RNA levels were higher in patients with the absence of retinal lesions (P = 0.008). In three patients, the HIV load in the eye largely exceeded that of plasma. These three patients had all bilateral anterior uveitis and/or vitritis without retinal lesions and exhibited no evidence of other intraocular infectious agents causing uveitis than HIV itself. Conclusion: The eye can form a sanctuary where HIV might replicate and cause an inflammatory reaction. © 2011 Wolters Kluwer Health | Lippincott Williams & Wilkins.