Human Immunodeficiency Virus (HIV) causes an infection that is spread through certain body fluids and attacks the body’s immune system. Specifically, the virus infects and destroys T Cells (CD4 + T cells) that the body uses to fight off infections. Despite advances in treatment, HIV remains an epidemic that has tremendous human, social, and economic impact around the world. According to the CDC, approximately 36.9 million people in the world were living with HIV at the end of 2014—17.1 %, or over 6.3 million, of whom did not know they were infected [1]. The CDC estimates nearly 2 million new infections a year.

The disease is characterized by an early stage (which may or may not occur in everyone), a latency stage, and progression to advanced disease or AIDS (acquired immunodeficiency syndrome). The early stage includes flu-like symptoms—fever, chills, rash, night sweats, muscles aches, sore throat, fatigue, swollen lymph nodes, and/or mouth ulcers—and can last anywhere from a few days to weeks. The latency stage, where viral replication is low, may have little to no symptoms at all. Finally, advanced infection, or AIDS, occurs when CD4 + cell count is below 200 cells per microliter and is exemplified by rapid weight loss, fever or profuse night sweats, fatigue, prolonged lymph node swelling, diarrhea, mouth/anus/genital sores, memory loss, depression, and/or red to purple blotches under the skin, mouth, nose, or eyelids. Ocular manifestations can occur at any stage of the disease; but most commonly occurs in advanced AIDS (CD4 + <50 cells per microliter).

Ocular manifestations can occur in up to 70–80 % of untreated HIV infected persons—more than half of which are associated with uveitis [2]. However, the prevalence of HIV-associated uveitis in the HIV or AIDS population is not known. Regardless, it is important to note that uveitis can occur in any stage of HIV infection and is caused by a number of distinct etiologies. Importantly, the characteristics of the uveal involvement reflect the pathology of the inciting disease process. The most common conditions causing uveitis in HIV infected persons are opportunistic infections (Cytomegalovirus [1, 3], Herpes zoster ophthalmicus, toxoplasmosis, etc.), but can also occur with ocular neoplasms associated with HIV, inflammation secondary to the HIV infection itself, HIV drug toxicity, or paradoxically, inflammatory dysregulation during the recovery of the immune system from HIV therapy (Immune Recovery Uveitis, IRU).

Anterior, posterior, and panuveitis have all been described in association with the various conditions causing uveitis in HIV. Anterior uveitis is typically seen with herpetic infections (Varicella Zoster Virus and Herpes Simplex Virus). It occurs with any CD4 + count and is commonly unilateral. It can often be associated with concurrent dermatitis, blepharoconjunctivitis, keratitis, or encephalitis. Patients can have decreased corneal sensation, elevated intraocular pressure, or patchy/sectoral iris atrophy [4, 5]. HIV drug toxicities also typically manifest with anterior uveitis. In particular, Cidofovir and Rifabutin, cause dose related inflammation when CD4 + count is less than 50 cells per microliter. The two drugs have subtle differences in that Cidofovir is granulomatous, associated with synechiae, can cause hypotony, and is more common in eyes with inactive CMV retinints; while Rifabutin is nongranulomatous, can be associated with hypopyon and is more common with concurrent antifungals and/or protease inhibitor use [6–9].

Posterior segment disease is the most common form of uveitis in HIV [10]. Necrotizing herpetic retinitis (CMV, VZV, HSV), occurs with CD4 + counts of less than 50 cells per microliter. CMV, the most prevalent opportunistic infection, presents with one or two active foci of retinitis and vitreous inflammation [11]. VZV and HSV retinitis (less than 5 % of HIV + patients) present more rapidly and with confluent areas of retinitis [12]. Toxoplasmic retinochoroiditis (~10 % of HIV + patients), occurs with CD4 + counts less than 250 cells per microliter. It typically presents with a single focus of retinitis adjacent to chorioretinal scars and is often unilateral [13]. Intraocular lymphoma can cause vitritis, retinitis, or retinal vasculitis with insidious onset in patients with CD4 + counts less than 50 cells per microliter [14]. Immune recovery uveitis, or paradoxical inflammation with reconstitution of CD4 + counts during therapy, most often occurs in eyes with inactive CMV retinitis. Inflammation of the vitreous is typical, but can involve the anterior chamber as well. Complications that have been described include macular edema, epiretinal membrane formation, vitreomacular traction syndrome, retinal neovascularization, and cataract [15–17]. Uveitis that is caused directly by inflammation of the virus itself also occurs at CD4 + counts less than 50 cells per microliter. Distinctly, it is typically moderate and examination reveals a lack of active retinitis [18].

Isolated choroiditis is most commonly seen with two types of infections: Pneumocystis carinii choroiditis and Cryptococcal choroiditis. Pneumocystis is typically bilateral, has multifocal choroid lesions, is associated with some vitreous inflammation but there is limited retinal hemorrhage. Cryptococcal infection presents similarly, but is associated with retinal hemorrhage and can have meningeal involvement.

Laboratory tests used to identify the cause of uveitis in HIV + patients should complement the history and physical exam. After a thorough history is obtained to identify exposures and past medical events, followed by a physical exam that characterizes the laterality, severity, and anatomic structures involved in the disease process, CD4 + count can narrow the differential. If infectious processes are highest on the differential, serologic, or vitreous sampling is typically available (PCR, antibody analysis, culture, etc.). Neoplastic etiologies require biopsy and histologic analysis, while drug toxicities and IRU require an astute clinician to recognize the possibility of these complications. It is also important to evaluate for the causes of uveitis in HIV negative patients, especially if a patient presents with adequate CD4 + reconstitution. Specifically, sarcoidosis (10–20 % of all uveitis in adults) is screened for with a chest X-ray and serum angiotensin-converting enzyme. Syphilis and TB should also be tested for using serum antibody analysis and the Mantoux test, respectively.