AIDS Dr. Amitabha Basu MD

Etiology Human Immunodeficiency Virus Name : retrovirus HIV-1, HIV-2 First described in 1981

Note the central core and the outer envelope.

Target cells of HIV CD4 cells Macrophages Dendritic cells Microglial cells

Type of HIV infectivity Macrophage-tropic (M-tropic) strains M-tropic strains use CCR5 of macrophage/ monocytes T-tropic strains T-tropic strains bind to CXCR4 of T cells If these receptors are not present patients are resistant to HIV infection !!!!!

HIV genome and function GAG Formation of viral core POL Formation of reverse transcriptase ENV Formation of gp120 and gp41

Infection: entry of HIV through damaged mucosa followed by underlying process

General Pathogenesis – 1 of 2 gp120 of HIV binds with CD4+ T cell. Then the HIV enter CD 4+ cell with the help of gp 41. Formation of proviral DNA by reverse transcriptase: It can remain latent for years Or, it can start virion production. Host cell (CD 4+) lysis occur due to this new virion. Reduction in number of CD4+ cell→ infection.

General Pathogenesis – 1 of 2

General Pathogenesis – 1 of 2 Widespread lysis of CD4 cell produce : Depletion of CD4 cells. Altered CD4 : CD8 ratio. Loss of CD4 cell: Failure of Humoral immunity and cell mediated hypersensitivity reaction.

How HIV reaches Brain ? HIV infect macrophage. Macrophages acts as a reservoir and vehicle for HIV to reach CNS. In brain HIV infect neural cells.

Natural History of HIV infection Early acute phase. After 3-6 weeks Rash, Fever and Lymphadenopathy. Viremia. Seroconversion after 3-17 weeks. Self limiting CD 4+ > 500/cumm Asymptomatic HIV infection Chronic phase Maintain normal health (Duration= 10years avg.) > 500/ cumm Symptomatic HIV disease. AIDS defining condition. AIDS Chance of opportunistic infections or malignancy. CD4+ < 200/cumm Advanced HIV disease Multiple opportunistic infection and malignancies < 50/cumm

Aids and disease Opportunistic infection: Mycobacterium avium intercellulare, Pneumocystis carinii, CMV, Cryptococcus neoformans, toxoplasmosis etc. Tumors : Kaposi's sarcoma (KSHV, HIV), B cell Non Hodgkin's lymphoma. CNS : Opportunistic Infection, Primary Lymphoma, AIDS –dementia complex.

Pneumocystis carinii: commonest in lung Gomori methenamine silver stain

CMV inclusions in lung are seen here microscopically. Cytomegalovirus may cause disseminated disease, although, more commonly, it affects the eye and gastrointestinal tract

Mycobacterium avium complex (MAC): Acid fast stain Patients with AIDS have reactivation of latent pulmonary disease as well as outbreaks of primary infection.

Candida albicans is seen here as an invasive process in the esophagus with PAS staining. Candidiasis is the most common fungal infection in patients with AIDS. Upper respiratory tract. Oral cavity.

Cryptococcus neoformans (common in CNS) : narrow-based budding seen in CSF: India ink preparation. T. gondii, another frequent invader of the central nervous system in AIDS

Histoplasma capsulatum in macrophage of Lympnnode,also involve brain

Non-Hodgkin's lymphomas seen in the central nervous system with AIDS are essentially clonal expansions of Epstein-Barr virus infected lymphocytes

Slims disease Central Africa, health workers diagnosed a disease causing severe weight loss and diarrheoa, which they called 'Slims Disease' . Agent: Cryptosporidium, Isospora belli, or microsporidia, Salmonella .

Heart Infective endocraditis: Staphylococcus aurous/CMV. Myocarditis: Trypanosoma cruzi

Diagnosis CD 4 cell count below 200 cell/ micro liter. ELISA Western blot.

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