Introduction
AIDS Infection caused by HIV-1 that results into weakened immune system with the increased risk of Opportunistic infections and malignant tumors. Additionally neurologic complications can occur.
Epidemiology
MODE OF TRANSMISSION
1-Sexual contact with HIV patient.
2-Parentral injection like IV drug abusers and blood transfusion.
3- From the Pregnant mother to the fetus (Vertical transmission)
RISK GROUPS
Five major risk groups
1-Homosexuals and bisexuals. The HIV virus enters via lymphocytes of semen through injured rectal mucosa.
2-IV drug abusers sharing contaminated needles about 25% of HIV patients.
3-Hemophilics (0.5%) due to the frequent need of large amounts of pooled VIII factor infusion.
4-Blood component recipient the incidence is markedly decreasing due to the optimum precautions.
5-Heterosexual contacts of high-risk people, hemodyalisis patients.
ETIOLOGY
Properties of HIV-1:
Human type C retrovirus belonging to Lentivirus. The virus is closely related to HIV-2 which cause similar disease in west Africa.
Non transmitting cytopathic virus causing T lymphocytes destruction The Lipid envelope is important for the mechanism of infection. Two viral glycoprotein gp120 and gp 41.
The virus core consists of major cuspid protein, genomic RNA, nucleocaspid protein and three enzymes protease, integrase and reverse transcriptase.
Pathogenesis of HIV infection and AIDS
1-CD4 T lymphocytes depletion is the main pathology
2-High affinity of gp 120 on HIV-1 to CD4 antigen
3-The gp 41 undergoes conformational changes and allow the virus to enter the cells.
4-Viral genome undergo reverse transcription and the pro-viral DNA becomes integrated into the host genome
5-The viral genome undergoes transcription, translation and viral propagation will occur only with T cell activation If activation does not.
6-Early in the course HIV-1 virus colonize lymph nodes (follicular dendritic cells act as reservoir)
7-viral replication results into T cell depletion occurs by cell lysis (one to two billion CD4 T cell lysis occurs daily). In the early course of the disease regeneration may compensate. Activation of apoptotic pathway (programmed cell death) and cytotoxic T lymphocytes mediated killing.
8- Major abnormalities of the immune function in HIV include decrease lymphocytes number: Loss of CD4 helperT cells and inversion of CD4:CD8 ratio. Decrease T cell function with preferential loss of memory T cell. T cell hypofunction results into depressed delayed hypersensitivity reaction and increase the incidence of opportunistic infections and neoplasms. Decrease proliferative response to mitogens and alloantigen as well as cellular cytotoxity and IL2 and TNFα production. Additionally, T helper cell function and B cell antibody production are reduced.
D- Polyclonal B cell activation results into hypergammaglobulinemia and circulating immune complexes. Altered monocytes and macrophage’s function. Decreased HLA (Human leucocytes antigen) class II expression as well as reduction in IL1, IL6, TNF production.
NATURAL HISTORY OF AIDS INFECTION
Three phases
1-Acute phase of AIDS
It is the initial phase in an immune-competent patient and consists of non-specific manifestations fever, sore throat. It is characterized by high viraemia load with modest CD4 reduction. This is followed by the virus specific immune response characterized by seroconversion( Serological tests can detect the virus) return of CD4 count to normal and decrease in viremia however viral replication continues in lymphoid organs.
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2-Middle phase (Chronic phase)
Usually asymptomatic or associated with lymphadenopathy(lymph nodes enlargement) and mild opportunistic infection. Virus replication occurs in lymphoid tissue. Modest CD4 reduction occurs. If persistent lymphadenopathy is associated with fever and rash this signifies acute decompensation and impending crisis.
The chronic phase usually lasts 7 to 10 years except in rapid progressors it lasts only 2-3 years. In the non-progressors they can remain asymptomatic more than ten years. As long as the CDC count remains above 500/µL the patient is asymptomatic.
3-Final crisis AIDS phase
Breakdown of immune defense. It is characterized by marked viraemia and prolonged fever greater than one month, fatigue, weight loss and diarrhea. Marked CD4 reduction less than 500/µl.
After some interval: The AIDS defining conditions (neurological), serious opportunistic infections and secondary neoplasms. The CDC count drops below 200/µL.
CLINICAL PICTURE:
Opportunistic infections:(Occurring only in the immune-suppressed patients)
Commonest A-Protozoal and helminthic Pneumocystis Jirovicci (pneumonia), Toxopalsma (pneumonia), cryptosporidiosis (enteritis). Fungal : Candidiasis (oesophageal and pulmonary);Cryptococcosis(Central nervous system); Coccidioidomycosis (Disseminated) and histoplasmosis(disseminated infection also). Also, Bacterial Aatypical mycobacteria(MAC), Mycobacteruim tuberculosis(pulmonary or extra-pulmonary), Nocardiosis (Pneumonia, meningeal), Salmonella (disseminated). Viral Cytomegalovirus (pulmonary, retina, central nervous system or disseminated infection), Herpes Simplex virus (localized or disseminated), Varicella zoster (localized or disseminated) and progressive multifocal leucoencephalopathy.
The opportunistic infections is the cause of death in 80 percent of cases with the incidence markedly decreased due to effective anti-retroviral therapy.
Pneumocystisis Pneumonia caused by pneumocystitis Jirovicii with higher incidence if CD4 cells less than 200/µL. Other common opportunistic infections include : Recurrent candidal infection of the mucous membrane. Disseminated cytomegalo virus diseases, Disseminated T.B and MAC diseases, Crytococcal meningitis, Salmonella enteritis.
2-Malignant tumors
Commonest one is Kaposi sarcoma. Additionally, HIV infection increases significantly the risk of Non-Hodjkin lymphoma; Cancer cervix in women and primary brain lymphoma.
KAPOSI SARCOMA
It is the most common neoplasm in AIDS with the Incidence has markedly decreased with the introduction of retroviral therapy. Also, the occurrence is higher in homosexuals than IV drug abusers. It can occur early or late in the course of AIDS. The tumor is multi-centric and aggressive. It occurs in the skin, mucous membranes, GIT, lung and lymph nodes. The tumor is caused by Kaposi sarcoma Herpes virus (KSHV) or human Herpes virus 8 (HHV-8)