HIV

Abstract

Acquired immunodeficiency syndrome (AIDS) was first recognized in Los Angeles and New York in 1981 when outbreaks of what was then called Pneumocystis carinii pneumonia (PCP; now called pneumocystis pneumonia) and Kaposi’s sarcoma were observed in previously healthy young men. Before this date, both conditions were very rare and restricted almost exclusively to immunocompromised patients. Epidemiologic data collected at the time suggested that a single blood- and semen-borne virus had predisposed these patients to infection, but it was not until several years after this outbreak that Barré-Sinoussi and associates in Paris and Gallo and associates in the United States independently isolated what was later termed the human immunodeficiency virus (HIV), now known to be the cause of AIDS.

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FormalPara Core Messages

• Human immunodeficiency virus (HIV) is a retrovirus that may lead to development of acquired immunodeficiency syndrome (AIDS).

• AIDS is a condition characterized by severely compromised cell-mediated immunity, predisposing patients with HIV/AIDS to opportunistic infections and neoplasms.

• It is estimated that about 0.8 % of the world’s population is infected with HIV [135]. Of these patients, more than 90 % are unaware that they are infected, and up to 70 % have ocular complications related to HIV/AIDS [21].

• HIV retinopathy is the most common retinal manifestation of HIV/AIDS. It is characterized by the formation of cotton-wool spots, hemorrhages, and microaneurysms, and it is typically asymptomatic.

• Important ocular infections seen in patients with HIV/AIDS include CMV retinitis, the most common, VZV herpetic retinitis, toxoplasmic retinochoroiditis, syphilis, Pneumocystis jirovecii choroiditis (PCP), Mycobacterium avium-intracellulare, Mycobacterium tuberculosis, and cryptococcal choroiditis.

• Noninfectious causes of uveitis observed in patients with HIV/AIDS include neoplastic disease, drug-induced uveitis, and immune recovery uveitis (IRU).

1 Definition

Acquired immunodeficiency syndrome (AIDS) was first recognized in Los Angeles and New York in 1981 when outbreaks of what was then called Pneumocystis carinii pneumonia (PCP; now called pneumocystis pneumonia) and Kaposi’s sarcoma were observed in previously healthy young men. Before this date, both conditions were very rare and restricted almost exclusively to immunocompromised patients. Epidemiologic data collected at the time suggested that a single blood- and semen-borne virus had predisposed these patients to infection, but it was not until several years after this outbreak that Barré-Sinoussi and associates in Paris and Gallo and associates in the United States independently isolated what was later termed the human immunodeficiency virus (HIV) [4, 40], now known to be the cause of AIDS.

The World Health Organization (WHO) defines AIDS as a disease of compromised cell-mediated immunity (an “AIDS-defining illness”) occurring in a person with no known cause for immunodeficiency other than the presence of HIV. The major diseases associated with HIV/AIDS are listed in Table 111.1. The Centers for Disease Control and Prevention (CDC) definition also includes HIV+ adults with a CD4+ count of less than 200 cells/μl.

Table 111.1 Recognized AIDS-defining illnesses (CDC category C)

It is estimated that 33.2 million people are infected with HIV worldwide, with approximately 2.5 million new infections and 2.1 million AIDS-related deaths in 2007 [134]. The prevalence of HIV infection appears to be stabilizing, with a decline in the incidence and improved survival of patients living with HIV/AIDS. However, the pandemic persists in several areas, including (A) the severe epidemic in sub-Saharan Africa, which accounts for 65 % of all new HIV infections, where an estimated 22.5 million persons are infected and where AIDS remains as the leading cause of death, and (B) global epidemics in high-risk populations including IV drug abusers, prostitutes, and men who have sex with men [134].

2 Clinical Manifestations

2.1 General Involvement

Acute HIV infection often manifests as a flu-like illness, followed by an asymptomatic period that may last from 2 to 10 years and during which CD4+ helper T cells typically decline in number. Patients frequently develop generalized lymphadenopathy and may experience malaise, diarrhea, weight loss, fever, and chills. Later on, as a consequence of declining cell immunity, these patients may manifest clinical signs related to opportunistic infections or neoplasms. These manifestations will depend on the involved organ.

2.2 Ocular Involvement

Up to 70 % of patients infected with HIV exhibit clinical signs of ocular disease, and postmortem findings suggest that the prevalence of ocular involvement may be as high as 95 % [62, 102]. HIV has been detected in most parts of the eye, including structural components, the aqueous humor [69], the vitreous [127], and the tear film [38]. The virus appears to have a particular affinity for the retina. The spectrum of ocular disease varies substantially between industrialized and developing countries due to poorer medical care and treatment availability [7, 21].

2.2.1 HIV Retinopathy

In the pre-HAART era, HIV retinopathy occurred in 40–60 % of patients with AIDS [35, 54], with the prevalence being inversely related to the degree of immune compromise [71]. Characteristic AIDS-related retinopathy includes the formation of cotton wool spots, hemorrhages, and microaneurysms [21, 35, 43]. Cotton wool spots are produced by focal areas of microvascular closure in the inner retina [102]. Hemorrhages and microaneurysms are also found in the superficial retina, typically along or within the vascular arcades. The presence of HIV antigen in retinal endothelial cells has been suggested to play a role in the development of microangiopathy, while other pathogenic hypotheses have included immunoglobulin deposition and rheological changes secondary to hyperviscosity and increased leukocyte rigidity [31, 35, 74, 77, 102, 105, 133].

While patients with HIV retinopathy are typically asymptomatic, the microvasculopathy may contribute to several processes, including electroretinographic abnormalities, color vision loss, visual field changes, progressive optic atrophy, and diminished contrast sensitivity [21]. While unproven, HIV retinopathy-induced vascular damage is believed to also play a role in the pathogenesis of CMV infection [14, 30, 49, 53].

2.2.2 Ischemic Maculopathy

Ischemic maculopathy is an uncommon disorder of unknown pathogenesis that can cause profound vision loss in patients with HIV/AIDS [22]. Vision loss is typically abrupt and accompanied by opacification of the superficial retina, often in association with hemorrhage formation in or near the fovea. Angiographic findings may include an enlarged foveal avascular zone and mild staining of the juxtafoveal vessels. Ischemic maculopathy should be considered in all patients with HIV/AIDS who experience unexplained loss of vision.

2.2.3 Cytomegalovirus (CMV) Retinitis

CMV retinitis is the most common ocular OI in patients with AIDS and previously affected 30–40 % of HIV-positive patients in developed countries prior to the widespread use of HAART [50, 54] (also see Chap. 107). While the incidence of CMV retinitis has decreased substantially in recent years, it remains the leading cause of vision loss in HIV [124].

CMV is a double-stranded DNA herpesvirus. Retinitis typically occurs at CD4+ cell counts under 50 cells/μl [59, 60, 71]. Symptoms of CMV retinitis include blurred vision, visual field defects, and new-onset floaters or photopsia [110]. Clinical examination often reveals minimal anterior or posterior chamber inflammation and full-thickness focal or sectoral retinal whitening, often with associated intraretinal hemorrhages. Optic nerve involvement occurs in 5–10 % of patients and is associated with a poorer visual prognosis [20, 21]. CMV retinitis is bilateral in 30–50 % of patients [18] and can occur in association with other OIs of the retina or choroid. Retinal detachment is a common complication, reported in up to one-third of patients, and typically requires vitrectomy with silicone oil placement [21].

2.2.4 Non-CMV Herpetic Retinitis

Non-CMV herpetic retinitis is the second most common cause of posterior segment infection in patients with HIV/AIDS and may be caused by varicella-zoster virus (VZV) or herpes simplex virus (HSV) type 1 or type 2 (see also Chaps. 107 and 117). VZV retinitis is the most common of these entities, occurring in roughly 5 % of patients with AIDS, while HSV retinitis in this group is rare [21]. VZV and HSV produce a similar clinical picture, and clues to distinguish the two include the association of HSV retinitis with recent or concurrent encephalitis and association of VZV retinitis with recent or concurrent zoster dermatitis.

Two clinical forms of non-CMV herpetic retinopathy have been recognized, acute retinal necrosis (ARN) and progressive outer retinal necrosis (PORN), classically occurring in relatively healthy and severely immunosuppressed patients, respectively. Intermediary forms may also occur [136]. The majority of patients with either form have a history of extraocular VZV infection [5, 72], whereas 4–17 % of patients with HIV/AIDS develop necrotizing herpetic retinitis after herpes zoster ophthalmicus [82, 118]. PORN is a rare cause of necrotizing herpetic retinopathy seen in patients with severe immune suppression, including AIDS [62]. It is characterized as a rapidly progressive infection, primarily affecting the retina with early macular involvement and minimal vitritis. Ophthalmoscopic findings include multifocal and/or confluent deep yellow-white lesions and, with time, a “cracked mud” pattern of perivascular clearance [81]. Papillitis can also occur and bilateral involvement and retinal detachment are common. PORN is a difficult infection to diagnose and treat. It is commonly confused with CMV retinitis or ARN and tends to be poorly responsive to therapy with intravenous (IV) acyclovir, intravitreal ganciclovir, or foscarnet [32, 34, 81].

The following important features commonly seen in ARN help to distinguish it from PORN: the presence of moderate to severe vitritis, retinal vasculitis, less apparent involvement of the inner retina, and anterior segment involvement. ARN typically affects healthy adults but has been reported in patients with HIV/AIDS as well [58, 84, 118]. CD4+ cell counts tend to be higher than those observed in association with either CMV retinitis or PORN, a factor believed to contribute to the more severe vitreous inflammation observed in ARN [19]. Common symptoms of ARN include eye pain, floaters, and visual field defects. ARN commonly progresses to retinal detachment with proliferative vitreoretinopathy [37, 56]. Bilateral involvement occurs in 59–70 % of patients, often in a sequential manner [5, 21, 68, 91].

2.2.5 Toxoplasmosis

Toxoplasma gondii is a frequent pathogen in patients with HIV/AIDS but is a relatively uncommon cause of AIDS-related retinal infection, affecting less than 1 % of HIV-infected patients in the United States [16, 44, 62] (also see Chap. 138). Infection is more common in areas with a higher seroprevalence such as Brazil where the prevalence approaches 8 % [7, 21, 44]. Symptoms of ocular toxoplasmosis are nonspecific but may include eye pain, redness, and blurred vision [10, 39, 52]. Such symptoms are less common in CMV retinitis, and their presence can be used to help distinguish toxoplasmic retinochoroiditis from CMV retinitis.

The most important features that distinguish toxoplasmic retinochoroiditis from other forms of retinitis include (1) the presence of moderate to severe vitritis; (2) although relatively rare, the presence of adjacent or nearby chorioretinal scars; and (3) a smooth edge to the lesion (i.e., the absence of satellite or popcorn lesions at the leading edge, which are more characteristic of CMV retinitis). Differentiating toxoplasmic retinochoroiditis from other causes of retinitis can at times be challenging in patients with HIV/AIDS, however, but PCR-based analysis of intraocular fluids can be quite helpful [1, 25, 114, 137]. Positive serologies are supportive, although it is important to remember that the IgG may be negative soon after an acute infection and Toxoplasma-specific IgM titers have relatively poor sensitivity and specificity [106, 109]. All patients with HIV/AIDS thought to have toxoplasmic retinochoroiditis should undergo MRI scanning of the brain to rule out central nervous system (CNS) toxoplasmosis.

Compared to infection in immunocompetent patients, HIV/AIDS-related ocular toxoplasmosis is more commonly bilateral and multifocal [52], lesions can be larger, and vitritis can be more prominent. In addition, the characteristic retinochoroidal scars seen with immunocompetent infection are observed less commonly, suggesting that infections are more frequently acquired than reactivated [39, 51].

2.2.6 Syphilis

In the developed countries, syphilis is the most common bacterial ocular infection in patients with HIV/AIDS, historically affecting up to 2 % of patients [6] (also see Chap. 97). Recent estimates suggest that the current prevalence is on the order of 6–9 %, paralleling an increase in syphilis infections in general [3]. Additionally, patients with a history of successfully treated syphilis prior to HIV seroconversion may manifest a reactivation of latent infection [96].

Syphilis may produce either uveitis or neuro-ophthalmic disease in HIV-positive patients, who usually present with blurred or decreased vision. Concurrent skin disease is common. Posterior segment involvement is more common in HIV-infected patients and may include retinitis, choroiditis, retinochoroiditis, or papillitis [6, 100, 121, 128, 129]. Patients with HIV/AIDS are also more prone to bilateral disease than HIV-negative patients [121]. Other potential findings include anterior uveitis, intermediate uveitis, panuveitis, optic neuritis, and retinal vasculitis [13, 129]. A relatively common presentation is vitritis associated with either a solitary or multifocal chorioretinitis characterized by large, yellow-white, placoid, subretinal, and/or choroidal lesions [9, 41]. The lesions often produce RPE alterations and can exhibit central fading. Solitary lesions may be difficult to distinguish from toxoplasmic retinochoroiditis and CMV retinitis [128].

The diagnosis of ocular syphilis is based on clinical examination and supportive serologic testing, and most patients coinfected with HIV and syphilis exhibit the above features [80]. Serologic testing in patients suspected of having ocular syphilis, including either an RPR or VDRL-test, together with either FTA-ABS or MHA-TP-test may have decreased sensitivity in the setting of immune suppression [100]. Lumbar puncture and CSF analysis should be performed in all patients with ocular syphilis as up to 85 % of patients have concurrent CNS infection [6, 76, 87, 100]. All patients with syphilis should also be tested for HIV.

Syphilis may have a more aggressive course in patients with HIV/AIDS and may also be difficult to eradicate. Compared to non-HIV/AIDS patients, IV penicillin may need to be given at higher doses and for a longer duration. Current CDC guidelines recommend 18–24 million units of daily IV aqueous crystalline penicillin G for 14 days. Alternatively patients may be given 2.4 million units of intramuscular procaine penicillin daily plus 500 mg of oral probenecid four times daily for 10–14 days [120]. Any treatment for neurosyphilis should involve consultation with an infectious disease specialist. To monitor the response to treatment and for recurrence, both serum and CSF reagin titers should be measured each month for 3 months following the completion of treatment and every 6 months thereafter until the CSF white cell count normalizes and the CSF-VDRL becomes nonreactive [100].

2.2.7 Cryptococcus

Cryptococcal choroiditis is uncommon in patients with HIV/AIDS, despite the relatively high prevalence of CNS disease (also see Chap. 123). When Cryptococcus does infect the eye, however, it usually produces choroiditis as a result of either hematogenous spread from the lungs or direct extension from infected meninges [36]. Ocular infection with Cryptococcus is often subclinical and identified only at autopsy [92, 102]. Neuro-ophthalmic complications, on the other hand, are relatively common, occurring in 25 % of patients with cryptococcal meningitis, and should increase suspicion of C. neoformans [54].

Cryptococcal lesions typically appear as single or multiple, well-demarcated, yellow-white spots in the choroid or deep retina, ranging in size from 500 to 3,000 μm [46, 47]. The differential diagnosis of infectious choroiditis includes P. jirovecii (previously P. carinii), C. neoformans, and M. tuberculosis, which account for the majority of infectious choroiditis in HIV/AIDS. Less common entities include M. avium complex, H. capsulatum, Candida spp., and Aspergillus spp. [21]. Cryptococcal choroiditis can also involve the optic nerve, producing progressive optic atrophy and permanent visual loss [12, 112, 115]; these findings may help the clinician identify the offending organism.

Early diagnosis of ocular Cryptococcus and prompt initiation of therapy with systemic therapy are important to preserve vision in affected patients. Treatment depends on the presence of meningitis. Isolated choroiditis should be treated with IV fluconazole (400 mg/day) plus flucytosine (100–150 mg/kg/day) for 10 weeks. When meningitis is present, treatment includes IV amphotericin B (0.7–1 mg/kg/day) plus flucytosine (100 mg/kg/day) for 2 weeks, followed by IV fluconazole for at least 10 weeks. In some patients, the infection may progress to endophthalmitis, requiring vitrectomy and intravitreal amphotericin B in addition to IV therapy.

2.2.8 Choroidal Pneumocystosis

PCP is common in HIV/AIDS patients, with a prevalence approaching 80 % in untreated patients, and is often the presenting infection [48, 83, 119] (also see Chap. 135). Aerosolized pentamidine, used for PCP prophylaxis, has been associated with an increased risk of extrapulmonary infections and so is no longer used [98].

Although originally termed P. carinii, P. jirovecii is now the recognized name for the Pneumocystis pathogen in humans. In the eye, P. jirovecii preferentially infects the choroid producing characteristically bilateral, elevated, multifocal, creamy yellow-white lesions with little or no vitritis [35, 70, 111, 115, 122]. Pneumocystis choroiditis is typically asymptomatic, but a minority of patients may experience floaters or visual field defects.

P. jirovecii choroiditis is rare in the absence of systemic infection [70, 115], and so all patients found to have Pneumocystis choroiditis should be treated for presumed systemic infection. The lesions should regress following 3–12 weeks of treatment, leaving little or no residual RPE changes.

2.2.9 Neoplastic Diseases of the Choroid and Retina: Non-Hodgkin’s Lymphoma

Intraocular lymphoma is uncommon but has a higher incidence and carries a worse prognosis in patients with HIV/AIDS [28, 86] (also see Chap. 147). In one large retrospective study, the proportion of intraocular lymphoma as an AIDS-defining illness has risen from 4.4 to 6.3 % following the advent of HAART [28]. Symptoms include floaters and vision loss. Dilated ophthalmoscopic examination characteristically reveals vitritis overlying numerous subretinal yellow-white infiltrates [21, 33, 113, 117]. Intraocular lymphoma should be on the differential diagnosis in any HIV/AIDS patient with vitreal inflammation, necrotizing retinitis, or choroidal infiltrates, particularly in the context of poor response or disease progression with empiric therapy. All patients suspected of having intraocular lymphoma should have a lumbar puncture and a brain MRI since concurrent CNS lymphoma is quite common [85]. Treatment options include radiation and chemotherapy (see Chap. 147). Initial response may be robust, but the overall prognosis tends to be poor.

2.2.10 Drug-Induced Uveitis

Several medications used to treat patients with HIV/AIDS can cause uveitis, particularly rifabutin and cidofovir [15, 90, 116] (also see Chap. 155). Drug-induced uveitis often responds to intensive topical corticosteroid therapy, but the offending medication may need to be discontinued in patients with inflammation that is severe or unresponsive to corticosteroid therapy.

2.2.11 Immune Recovery Uveitis (IRU)

IRU is a noninfectious intraocular inflammation first recognized soon after the advent of HAART. It is seen in patients with quiescent CMV retinitis who experience a substantial increase in the CD4+ cell count following initiation of HAART [140], most probably due to expansion of previously depleted anti-CMV T-cell populations. Clinical findings include moderate to severe vitritis, cystoid macular edema, papillitis, epiretinal membrane formation, retinal neovascularization, and proliferative vitreoretinopathy [8, 11, 66, 108, 140]. Risk factors for IRU include a history of CMV retinitis involving more than 25 % of the retina and prior use of IV cidofovir [67]. The complications of IRU can be severe and vision threatening. While variably effective, current treatment options include prolonged use of topical, periocular, and intraocular corticosteroids [95].

3 Etiology and Pathogenesis

AIDS is caused by infection with the human retroviruses HIV-1 and HIV-2. HIV-1 accounts for the vast majority of cases worldwide, with HIV-2 seen predominantly in western Africa. These viruses are passed through bodily fluids, and the principal modes of infection are through sexual contact, through contact with blood or blood products, via contaminated IV needles, intrapartum or perinatally, or via breast milk. As such, the incidence of HIV infection is higher in groups with certain high-risk behavior, including men having sex with men and unprotected sexual intercourse, particularly if involving multiple partners and/or anal intercourse, and IV drug abusers.

HIV leads to immunosuppression by targeting and slowly destroying CD4+ cells, mainly CD4+ helper T cells and CD4+ monocytes. Shortly after becoming infected, most patients undergo a viremic stage, often associated with a mononucleosis-like syndrome known as the “acute antiretroviral syndrome.” During this phase, the virus is disseminated throughout the body but is relatively controlled by an antibody-mediated immune response. Despite this response, HIV is rarely cleared from the body. Instead the infection persists as a chronic, clinically latent infection, with a progressive depletion of CD4+ T cells. After some period of time, often 10 years or longer, CD4+ T-cell counts fall below a critical level (approximately 200 cells/μL), and patients become increasingly susceptible to opportunistic disease.

4 Diagnosis

Routine laboratory diagnosis of HIV infection is based on the demonstration of antibodies to HIV. Most patients seroconvert to HIV positivity within 4–10 weeks of exposure and over 95 % seroconvert within 6 months [17, 123, 125]. Enzyme-linked immunosorbent assay (ELISA) is an extremely sensitive and specific test for the presence of HIV antibodies. However, ELISA was designed to screen donated blood, not to diagnose infection. The most common confirmatory test in patients with a positive ELISA is Western blot, which detects anti-HIV antibodies of specific molecular weights.

5 Differential Diagnosis

Table 111.2 shows a list of typical HIV-related infections for various levels of immune deficiency. The ocular manifestations of HIV/AIDS also depend on the degree of immune suppression (Table 111.3). These manifestations may be divided into five major categories: noninfectious retinal microvasculopathy, opportunistic infections (OIs), neuro-ophthalmologic disorders, neoplasms, and drug-related complications [7, 23]. Uveitis can play a substantial role in OI, neoplastic disease, and drug-related complications. Table 111.4 shows the differential diagnosis of HIV-related uveitis within these categories (Table 111.5).

Table 111.2 Systemic disease in patients with HIV/AIDS by CD4+ cell count

Table 111.3 HIV-associated uveitis by CD4+ cell count

Table 111.4 Differential diagnosis of common causes of HIV/AIDS-related uveitis

Table 111.5 Uncommon causes of ocular infection in HIV/AIDS patients

6 Treatment

The cornerstone of management for HIV/AIDS is combination antiretroviral (ARV) therapy, known as HAART (highly active antiretroviral therapy). These medications fall into six classes: (1) nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs), (2) nonnucleoside reverse transcriptase inhibitors (NNRTIs), (3) protease inhibitors (PIs), (4) fusion inhibitors (FIs), (5) CCR5 antagonists, and (6) integrase inhibitors. NRTIs include zidovudine (AZT, ZDV), didanosine (ddI), zalcitabine (ddC), stavudine (d4T), lamivudine (3TC), abacavir (ABC), tenofovir (TDF), and emtricitabine (FTC). Coformulations include Combivir (3TC + ZDV), Trizivir (ABC + ZDV + 3TC), Epzicom (ABC + 3TC), Atripla (EFV + TDF), Truvada (FTC + TDF), and Atripla (EFV + FTC + TDF). NNRTIs include nevirapine (NVP), delavirdine (DLV), etravirine (ETR), and efavirenz (EFV). PIs include darunavir (DRV), fosamprenavir (FPV), indinavir, nelfinavir (NFV), ritonavir (RTV), saquinavir (SQV), tipranavir (TPV), lopinavir, and atazanavir (ATV). Kaletra is a coformulation of lopinavir and low-dose ritonavir. NNRTIs and PIs are extremely potent but commonly induce drug resistance when used as monotherapy and should only be used in combination with other ARVs.

A typical HAART regimen employs two or more NRTIs with either a PI or a NNRTI. Integrase inhibitors (e.g., raltegravir, RAL), fusion inhibitors (e.g., enfuvirtide, T20), and CCR5 antagonists (e.g., maraviroc, MVC) are newer treatment options that are not yet in widespread use. The decision to initiate HAART as well as specific regimens is based on the individual clinical situation and is beyond the scope of this chapter. Please visit the following Web sites for current guidelines:

• www.aidsinfo.nih.gov/Guidelines

• www.niaid.nih.gov/factsheets/treat-hiv.htm

See earlier sections as well as other chapters for details of the specific entities discussed above.

7 Prognosis

HAART has impacted the AIDS epidemic on several levels. In areas where it is widely available, it has improved both the quality and duration of life. HAART has led to a significant reduction in AIDS-related illnesses, hospitalizations, and deaths [27, 88, 89, 99, 103, 132]. Successful HAART can change HIV disease from an illness that was almost always a death sentence into a chronic but manageable condition.

HAART has changed the face of AIDS-related uveitis, with substantial impact on incidence, progression, and management. The most noticeable impact has been on CMV retinitis [45]. Recent studies have shown that HAART has reduced the incidence of CMV retinitis by about 75 % [63] and has reduced the odds of retinitis progression by 50 %, even among those patients with low CD4+ cell counts [57, 60]. As such, the rate of secondary complications, including retinal detachment, has decreased nearly 90 % [54, 61]. Paralleling these changes has been a substantial decline in CMV-related visual impairment and blindness [130, 131]. However, CMV retinitis can still occur in patients with CD4+ cell counts well above 100 cells/μL, however, and so regular screening is important, even for patients successfully treated with HAART [60, 61, 64, 65, 104].

The impact of HAART on non-CMV ocular OIs has paralleled that of CMV retinitis. Patients with non-CMV herpetic retinitis experience shorter durations of reactivation [107], and spontaneous regression of PORN has been described [139]. The prevalence of ocular toxoplasmosis [2] and Cryptococcus [29] in HAART-treated HIV/AIDS patients has also declined. PCP- and AIDS-related ocular lymphomas are similarly less common, and affected patients tend to survive longer [86, 94, 99]. In addition, HAART-induced immune reconstitution may enable the discontinuation of prophylactic treatment for many OIs, including CMV retinitis [55, 138], T. gondii [141], P. jirovecii [78], and C. neoformans [97].

Take-Home Pearls

• CMV retinitis remains the most common cause of infectious retinitis and ocular morbidity in patients with HIV/AIDS. Infectious retinitis not due to CMV is most commonly caused by other herpesviruses or toxoplasmosis.

• Proper diagnosis of HIV/AIDS-related ocular complications is critical because specific therapy is available for many of the more common disorders, because failure to diagnose can lead to severe and permanent vision loss, and because ocular disease may be the initial manifestation of an underlying disseminated infection.

• HAART has had a substantial impact on HIV in wealthy countries, including immune reconstitution for many patients with resultant improved survival and declines in opportunistic infections. However, HIV/AIDS remains a leading cause of death in developing countries, particularly sub-Saharan Africa.