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5 Cards in this Set
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AIDS: overview |
Most common cause of death by infection worldwide Sub-saharan Africa as most cases HIV - Retrovirus that causes AIDS. Reverse transcriptase that converts viral RNA into proviral dsDNA. - HIV-1 is most common cause of AIDS in the United States (HIV-2 more in Western Africa) - Virus cannot penetrate intact skin or mucosa. Ulceration of skin or mucosa must be present for the virus to enter CD4 T cells or dendritic cells in tissue. - Has three retroviral genes: gag gene for inner structural proteins. Env gene for synthesis of the viral envelope with outer structural proteins that give cell-type specificity (gp120 binds the virus to the host CD4 cell). Pol gene direct synthesis for reverse transcriptase, integrase and protease. |
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HIV: Modes of transmission |
Sexual transmission (80%) - Man to man by anal intercourse most common in US - Heterosexual most common in developing countries - Prior or current STDs increases the risk for HIV infection IV drug use - Rate is markedly increased in female partners of male IV drug users. Other modes - Vertical transmission via transplacental route during delivery and breast feeding. - Accidental needlestick is the most common cause of infection in health care workers. 0.3% seroconversion - Blood products: 1 in 2 million units transfused. Blood banks are screened. |
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HIV: Pathogenesis |
Major cells infected are CD4 T cells, macrophages, dendritic cells and astrocytes. - Cytotoxic to CD4 T cells - Macrophages contain large numbers of viral particles in cytoplasmic vacuoles but unlike CD4 T cells, they are not destroyed and so act as a reservoir. - Similar to macrophages, dendritic cells act as a reservoir. Primary infection due to HIV due to entry by virus through interrupted mucosal surfaces in the genital tract/anus where it infects CD4 T cells and dendritic cells in the underlying tissue. - Cells drain into lymph nodes and spleen where the virus is held in check by the patient's immune system. - Follicular dendritic cells in the germinal centres of the lymph nodes are the major reservoirs of the virus during early latent stages of the disease before the virus is released into the blood and causes an acute retroviral syndrome. |
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HIV: Lab tests |
ELISA (screening) - Anti-gp120 antibodies. Has a sensitivity of 100%. - New 4th generation screening tests, positive within 3-5 weeks; all in 3 months. Detect antibodies for HIV-1, HIV-2 and p24 antigen Western blot and nucleic acid assays (confirmatory) - Western blot is used if ELISA is positive or indeterminate - Positive test: presence of p24 antigen and gp41 antibodies, and either gp120 or gp160 antibodies - Test misses a significant number of people with HIV who have indeterminate test results - HIV1 RNA in vitro nucleic acid assays now replace the Western blot as a confirmatory tests. Specificity 100% p24 antigen (indicates active viral replication) - Present before anti-gp120 antibodies. - Positive before seroconversion and when AIDS is diagnosed (two distinct peaks) - Test is used by blood banks to screen for HIV; has markedly decreased the chance for contracting HIV by blood transfusion CD4 T-cell count (monitoring immune status) - Useful in determining when to initiate HIV treatment and when to administer prophylaxis against opportunistic infection HIV viral load (detection of actively dividing virus), marker of disease progression - Most sensitive test for diagnosis of acute HIV before seroconversion - Recommended at least one time per year |
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Natural Hx of HIV infection |
Acute phase - Approx 3-6 weeks after infection individuals experience fever, malaise and generalised painful lymphadenopathy which usually subsides within a few days - Greatest risk for contracting HIV is in the first few weeks of infection Asymptomatic carrier phase - This is an asymptomatic period that lasts between 2-10 years after contracting infection. - CD4+ T-cell count is >500 cells/mm3 - Viral replication occurs in follicular dendritic cells in the germinal follicles of lymph nodes and in macrophages. Cytotoxic T cells control but do not clear HIV reservoirs. |
