PG Series: HIV

The various manifestations of the disease are given in the table below:

HIV Virus:

• Lentivirus sub-family of retroviruses
• The HIV virion binds to the CD4T cell ® once in the cell its RNA is translated into DNA by viral reverse transcriptase ® this DNA then enters the nucleus & incorporates into the cell   genomes with the assistance of integrase ® this viral DNA is then capable of   directing protein synthesis of new viral proteins using infected cell’s apparatus
• AIDS is the end stage of the clinical infection by HIV. Following infection, a person may experience a flu-like illness. This is followed by prolonged asymptomatic phase and as the disease progresses; a person may contract common infections like tuberculosis and other opportunistic infections. This is followed by AIDS, the last stage characterized by AIDS defining illnesses like Pneumocystis carinii pneumonia (PCP), Oral candidiasis, CMV retinitis, Kaposi’s sarcoma and many others.
• Ocular complications affect 50-75% of HIV/AIDS patients in some point of their life.

A. Ocular adnexal and Anterior segment involvement in HIV:

1. Kaposi’s sarcoma:

• Kaposi’s sarcoma (KS) is a tumor caused by human herpesvirus type 8 (HHV8).
• It is more widely known as an AIDS-defining illness.
• It commonly causes skin lesions but can affect the oral cavity, gastrointestinal tract, respiratory tract and other viscera.
• Cutaneous lesion can be solitary, localized or disseminated and usually appear as a reddish, violaceous or bluish-black macules, papules, nodules or plaques.
• Treatment options include excision, cryosurgery, radiotherapy, chemotherapy or a combination therapy.
• HAART treatment can cause regression of lesions.

2. Molluscum contagiosum :

• Also known as water warts
• It is a viral infection of the skin and mucous membrane
• Caused by a double stranded DNA pox virus - molluscum contagiosum virus (MCV). 
• Characteristic skin lesion is a single small elevation with central umbilication.
• In AIDS patients, lesions are multiple, bilateral and involve trunk, axillae, antecubital and popliteal fossae, face, or genital/crural area apart from face and neck. They are difficult to eradicate and recur
• HAART therapy causes early regression and may cause resolution of lesions.
• Treatment options include local excision, medical management and laser therapy.
• Medical management includes 5% Imiquimod, podophyllotoxin, cantharidin, retinoin, trichloroacetic acid, combination of salicylic acid and lactic acid and cidofovir cream.

3. Herpes zoster Ophthalmicus:

• Caused by reactivation of chicken pox virus, also known as human herpesvirus 3.
• Younger non-diabetic patients without any other medical or surgical history should raise a suspicion of HIV/AIDS. Characterized by vesicles and gradual crusting in a well-defined dermatomal region.
• Other eye lesions such as corneal ulcers and scarring, uveitis, glaucoma, retinitis, cytoid macular edema, optic neuritis, nerve palsies, post herpetic neuralgia and post herpetic itch.
• Conventional treatment includes 800mg of oral acyclovir five times daily

4. Conjunctival Microvasculopathy:

• Causes: multifactorial like direct injury by the HIV virus itself, immune complex deposition, blood viscosity changes and vessel wall changes.
• Characterized by vascular contour changes like narrowing, dilatation, comma shaped vessels and aneurysms formation.
• Treatment is usually not needed.

5. Dry eyes:

• Long-term sequel of various other corneal and adnexal manifestations.
• Direct injury to the lacrimal glands by the HIV virus has also been implicated.

6. Infectious keratitis and scleritis:

• Infectious keratitis and scleritis due to viral aetiology is common in HIV/AIDS patients. They are characterized by recurrent attacks and are resistant to therapy.
• Bacterial and fungal keratitis is not as common as viral keratitis, but can occur in HIV/AIDS patients.
• Candida, microsporidial and fusarium solani keratitis should raise a suspicion of HIV/AIDS.

7. Squamous cell carcinoma of the conjunctiva:

• Seen in old male HIV/AIDS patients.
• But, its incidence has been increasing with many younger people affected; especially women.  

8. Anterior uveitis:

• Anterior uveitis is seen in HIV/AIDS patients in association with retinitis, retinochoroiditis or drug toxicity. CMV, HSV and VZV retinitis are usually associated with mild anterior segment reaction too. Severe anterior segment reaction should arouse a suspicion of toxoplasmosis, tuberculosis or syphilis.
• Antiretroviral drugs causing uveitis; Rifabutin and Cidofovir

B. Posterior Segment involvement in HIV:

1. HIV related retinal microangiopathy (Retinopathy):

• MC ocular lesion (before the introduction HAART)
• HIV retinopathy is a non-infectious involvement of the retina in HIV/AIDS patients
• It is a microvascular disorder characterised by cotton-wool spots + microaneurysm + retinal haemorrhages + telangiectic vascular changes + areas of capillary nonperfusion
• Not a vision threatening condition but its presence can be considered as a disease progressing sign.

2. CMV retinitis: See next question

3. Acute Retinal Necrosis:

• One or more foci of retinal necrosis with discrete border in peripheral retina
• Rapid progression with antiretroviral therapy
• Circumferential spread
• Evidence of occlusive vasculopathy with arteriolar involvement
• Prominent inflammatory reaction in vitreous & AC

4. Progressive Outer Retinal Necrosis:

• PORN consists of deep outer retinal lesions in a central retina.  
• With the progression of retinitis there is cleaning of areas around retinal vessels (“Cracked mud” appearance ).
• which is due to early removal of necrotic debris & edema from retinal tissue adjacent to the blood vessels
• Disease progresses rapidly & often results in a retinal detachment with in days or weeks.
• Because of the devastating nature off the inflammation vision may deteriorate from 6/6 to no light perception.

5. Toxoplasmic Retinochoroiditis:

• Less common than toxoplasma encephalopathy in AIDS patients.
• Toxoplasmic retino-choroiditis in HIV/AIDS patients usually differs from immunocompetent patients - lesions can be larger, multiple, bilateral, with minimal vitritis and may resolve without scars.
• Can present as multifocal or diffuse necrotizing retinitis, papillitis or retrobulbar neuritis, or outer retinal toxoplasmosis. Typical “Head light in a fog” picture is also found
• Prompt management is important as the disease usually progresses if not treated, unlike in immunocompetent individuals.
• Treatment includes a sulfonamide with a non-sulfonamide, steroids and folic acid supplements. Pyrimethamine with sulfadiazine works synergistically against the tachyzoite form
• Long term prophylaxis continues till patients CD4 counts raise above 200 cells /ml for six or more months and then can be discontinued.

6. Ocular tuberculosis:

• Tuberculosis is the most common opportunistic systemic infection in HIV or AIDS patients, although ocular tuberculosis is not that common.
• Ocular tuberculosis can affect any part of the ocular tissue and adnexa.
• Posterior segment manifestations include choroiditis, choroidal granulomas, endophthalmitis, subretinal abscess and panophthalmitis.
• PCR and histopathologic examination are very helpful in the definitive diagnosis of ocular TB.

7. Ocular syphilis:

• Ocular syphilis tends to be aggressive, severe and relapsing in HIV/AIDS patients.
• MC intraocular bacterial infection in HIV/AIDS patient and all patients with ocular syphilis should be screened for HIV .
• Anterior segment involvement = conjunctival chancre, conjunctivitis, gummata, scleritis and anterior uveitis.
• Posterior segment lesions = chorioretinitis, optic neuritis, papilloedema or optic perineuritis.
• Up to 38% of HIV-positive patients can be seronegative despite active syphilitic disease, making the diagnosis more difficult. 
• Diagnostic serologic tests include:
  • Screening test like rapid plasma reagin test
  • Confirmatory tests like fluorescent treponemal antibody absorbent tests
• Treatment is high-dose IV penicillin G 12-24 million units/day for 14 days.

8. Fungal infections:

• The most common intraocular fungal infections are Candida and Cryptococcus
• Disseminated candida infection is characterized by multiple fluffy-creamy-white chorioretinal lesions with overlying vitreous inflammation and snowballs.
• Cryptococcus neoformans is also a common fungal infection in AIDS. It primarily manifests as meningitis, resulting in papilloedema, optic neuropathy. Chorioretinitis and cranial nerve palsies are also seen, which indicate a poor prognosis. 
• Disseminated histoplasmosis has a fulminant course and high mortality in HIV/AIDS patients.

9. Lymphomas:

• Non-Hodgkins Lymphoma (NHL) can be seen in HIV patients of any age and a CD4 cell count of<50 cells/mL. It is characterized by the presence of prominent vitreous cells, with or without subretinal exudation
• Radiotherapy and/or chemotherapy are helpful. Interferon alpha has also been used as a part of the treatment modality.

10. Neuro-ophthalmic lesions:

• The common Neuro-ophthalmologic manifestations in HIV/AIDS include optic neuropathy, cranial nerve palsies, papilloedema and optic atrophy.
• Common causes of neuro-ophthalmic involvement are: toxoplasmosis, cryptococcosis, VZV, CMV, progressive multifocal leukoencephalopathy, CNS and orbital lymphoma.

11. Immune recovery uveitis: 

• Immune recovery uveitis (IRU) is a part of the immune reconstitution inflammatory syndrome (IRIS), which has been described in other organs and with other opportunistic infections.
• The AIDS Clinical Trial Group defined IRU as a 'decrease in vision and at least two of the following signs in the absence of active CMVR: presence of >2+ inflammatory cells in vitreous by slit lamp examination, cystoid macular edema (CME) or epiretinal membrane formation in patients receiving potent antiretroviral therapy with evidence of immune reconstitution'.
• Major risk factors of IRU are: A low CD4 count, HLA A8-18, extent of retinitis and history of treatment with cidofovir are significant risk factors for IRU at the time of starting HAART.