CLINICAL MANIFESTATIONS OF HIV Dr. Mrs. S. Kanitkar, Dept. of Medicine, Dr. D. Y. Patil Hospital

Clinical Manifestations Clinical consequences of HIV encompass a wide spectrum Range from acute syndrome associated with primary infection to prolonged asymptomatic state to advanced disease Current CDC classification system categorizes persons on basis of clinical conditions associated with HIV & CD4 + counts Diagnosis of AIDS is made in anyone with HIV infection & CD4 + count < 200/ µL AND in anyone with HIV infection who develops one of HIV-associated diseases considered to be indicative of severe defect in cell mediated immunity ( Category C )

Classification System for HIV infection CLINICAL CATEGORIES CD4 + T-cell categories A - ASYMPTOMATIC Primary HIV or PGL B – SYMPTOMATIC Not A or C conditions C – AIDS-indicator conditions > 500 / µL A1 B1 C1 200 – 499 / µL A2 B2 C2 < 200 / µL A3 B3 C3

Cont… CATEGORY A One or more conditions listed below Conditions in categories B & C must not have occurred Asymptomatic HIV infection Persistent generalized lymphadenopathy Acute HIV infection or history of acute HIV infection

Cont… Candidiasis, Oropharyngeal (thrush), Vulvovaginal CATEGORY B Symptomatic conditions not included in category C Candidiasis, Oropharyngeal (thrush), Vulvovaginal Cervical dysplasia , cervical carcinoma in situ Fever/diarrhea lasting > 1 month Oral hairy leukoplakia Herpes zoster Idiopathic thrombocytopenic purpura Listerosis Pelvic inflammatory disease Peripheral neuropathy

CATEGORY C (AIDS defining illness) Candidiasis – bronchi, trachea, lungs or esophageal Cervical cancer – invasive Coccidiomycosis – disseminated or invasive Cryptococcosis – extrapulmonary Cytomegalovirus disease ( other than liver, spleen or nodes ) CMV retinitis ( with loss of vision ) Encephalopathy – HIV related Herpes simplex – chronic ulcer(s) or bronchitis or esophagitis Histoplasmosis – disseminated or extrapulmonary Kaposi’s sarcoma Lymphoma – Burkitt’s Mycobacterium avium complex or M. Kansasii Mycobacterium tuberculosis – any site Pneumocystis carinii pneumonia Pneumonia - recurrent Progressive Multifocal Leukoencephalopathy Toxoplasmosis of brain Wasting Syndrome due to HIV

STAGES OF HIV INFECTION ACUTE HIV SYNDROME ASYMPYTOMATIC STAGE – CLINICAL LATENCY SYMPTOMATIC DISEASE

THE ACUTE HIV SYNDROME Develops 3 – 6 weeks after primary infection Syndrome is typical of an acute viral syndrome Symptoms usually persist for 1 to several weeks & gradually subside Lymphadenopathy ( ~ 70 % individuals ) CLINICAL FINDINGS : - Fever - Meningitis - Pharyngitis - Encephalitis - Lymphadenopathy - Peripheral neuropathy - Headache/Retroorbital pain - Myelopathy - Lethargy/Malaise - Erythematous maculo- - Anorexia/Weight loss papular rash - Nausea/Vomiting/Diarrhea - Mucocutaneous ulcer

ASYMPTOMATIC STAGE – CLINICAL LATENCY Infected individual remains well with no evidence of disease except for possible presence of persistent generalized lymphadenopathy HIV disease with active virus replication is ongoing & progressive during asymptomatic period When CD4 + T cell count falls to < 200/ µL the immunodeficiency is severe enough to cause clinically apparent disease Median time for untreated patients to develop clinical disease is ~ 10 yrs.

SYMPTOMATIC DISEASE Symptoms can occur at any time during the course of HIV infection More severe & life-threatening complications occur in patients with CD4 + T cell counts < 200/ µL Approx. 60 % deaths among AIDS patients are direct result of an infection other than HIV P. carinii, Viral hepatitis & non-AIDS-defining bacterial infections are common infections

NEUROLOGICAL MANIFESTATIONS Seen in 40 – 60 % patients Neurologic disorders : OPPRTUNISTIC INFECTIONS - Toxoplasmosis - Cryptococcosis - Progressive Multifocal Leukoencephalopathy - Cytomegalovirus - Syphilis - Mycobacterium Tuberculosis - HTLV-I infection NEOPLASMS - Primary CNS Lymphoma - Kaposi’s sarcoma RESULT OF HIV-1 INFECTION - Aseptic meningitis - AIDS dementia complex MYELOPATHY - Vacuolar myelopathy - Pure sensory ataxia - Paresthesia / dysesthesia PERIPHERAL NEUROPATHY - Guillian-barre syndrome - CIDP - Mononeuritis multiplex - Distal symmetric polyneuropathy MYOPATHY

Cont… Few most common CNS manifestations : Toxoplasmosis - fever, headache, drowsiness - MRI : multiple ring enhancing lesions with marked surrounding edema & mass effect Primary CNS Lymphoma - late stage HIV - tumours usually high grade, diffuse, -cell neoplasm - closely associated with EBV - MRI – usually single lesion, minimal edema

Cont… Progressive Multifocal Leukoencephalopathy - J C papova virus - occurs in 2-3 % AIDS pts. at very low CD4 counts - rapidly progressive demyelinating disease - slow onset visual field defects, ataxia or hemiparesis - MRI : non-enhancing white matter lesions without surrounding edema Cryptococcal meningitis & abscess

RESPIRATORY MANIFESTATIONS Most common manifestation is PNEUMONIA Causes : bacterial infections S. Pneumoniae, H. influenza occur at any Staph. Aureus stage Pseudomonas in later Nocardia stages P. Carinii : - 1st major indicator disease for HIV - Incidence has fallen due to prophylaxis / HAART - Dry cough, fever, disproportionate breathlessness - X-ray chest may be normal, may show perihilar ground glass changes, ARDS picture or atypical appearance

Cont… Other causes of pulmonary infiltrates : Mycobacterium tuberculosis : - greater risk of reactivation of latent infection, acquiring TB from an open contact, developing progressive primary disease, developing disseminated disease - affects HIV adversely with enhanced replication & acceleration of disease - when CD4 > 200 cells/cmm, disease is more likely to be reactivated upper-lobe open cavitatory disease - in later stages miliary, atypical, extra-pulmonary TB become more common Kaposi’s sarcoma Lymphoma

GASTROINTESTINAL MANIFESTATIONS OF AIDS ORAL LESIONS : Oral candidiasis ( thrush ) - often asymptomatic but may cause mouth pain, dyspahgia Oral hairy leukoplakia – corrugated white plaques running vertically on side of tongue Herpes simplex virus – painful oral lesions ESOPHAGEAL LESIONS : Common organisms are Candida, CMV, HSV Candidiasis – difficulty in swallowing with diffuse pain & usually afebrile Esophageal CMV – presents with gradual onset localised pain on swallowing, dysphagia, fever & weight loss HSV – difficulty in swallowing along with oral lesins GASTRIC LESIONS : Gastrointestinal CMV occurs in upto 1/3rd patients

Cont… SMALL BOWEL & COLON LESIONS : Acute or chronic diarrhea a frequent complication May be caused by medications, oppurtunistic infections or common organisms Drugs causing diarrhea : lopinavir, nelfinavir, didanosine, saquinavir ACUTE DIARRHEA CHRONIC DIARHHEA Salmonella Cryptosporidia Clostridium difficle Microsporidia Enteric viruses Isospora belli Idiopathic Mycobacterium avium Cytomegalovirus

Cont… TUMOURS OF GIT : Kaposi’s sarcoma, NHL, cloacogenic Ca of rectum, squamous cell Ca of rectum & anus Kaposi’s sarcoma is most common MALNUTRITION & WASTING : Factor’s contributing malnutrition : hypermetabolic state, dyspahgia, AIDS enteropathy

SKIN DISEASES Seborrhoeic dermatitis – itchy follicular rash Viral infections - Herpes simplex – may affect lips, mouth, skin, anogenital area - Varicella zoster – severe multi-dermatomal persistent/recurrent, may become disseminated - Human papilloma virus – usually anogenital lesions - Molluscum contagiosum – 2 to 5 mm papules with central umbilicus Bacterial infections - Staph. Aureus folliculitis/cellulitis Scabies – intensely pruritic encrusted papules

NEOPLASTIC DISEASES KAPOSI’S SARCOMA LYMPHOMAS

TH NK YOU !!