As alluded to earlier, mother-to-infant transmission is the major cause of pediatric AIDS. Infected mothers can transmit the infection to their offspring by three routes: (1) in utero by transplacental spread; (2) during delivery through an infected birth canal; and (3) after birth by ingestion of breast milk. Of these, transmission during birth (intrapartum) and in the immediate period thereafter (peripartum) is considered to be the most common mode in the United States. The reported transmission rates vary from 7% to 49% in different parts of the world. Higher risk of transmission is associated with high maternal viral load and low CD4+ T cell counts as well as chorioamnionitis. Fortunately, anti-retroviral therapy given to infected pregnant women in the United States has virtually eliminated mother-to-child transmission, but it remains a major source of infection in areas where these treatments are not available.
Much concern has arisen in the lay public and among healthcare workers about the spread of HIV infection outside the high-risk groups. Extensive studies indicate that HIV infection cannot be transmitted by casual personal contact in the household, workplace, or school. Spread by insect bites is virtually impossible. Regarding transmission of HIV infection to healthcare workers, an extremely small but definite risk is present. Seroconversion has been documented after accidental needle-stick injury or exposure of nonintact skin to infected blood in laboratory accidents. After needle-stick accidents, the risk for seroconversion is believed to be about 0.3%, and antiretroviral therapy given within 24 to 48 hours of a needle stick can greatly reduce the risk of infection. By comparison, approximately 30% of those accidentally exposed to hepatitis B–infected blood become seropositive.
HIV is a nontransforming human retrovirus belonging to the lentivirus family. Included in this group are feline immunodeficiency virus, simian immunodeficiency virus, visna virus of sheep, bovine immunodeficiency virus, and the equine infectious anemia virus.
Two genetically different but related forms of HIV, called HIV-1 and HIV-2, have been isolated from patients. HIV-1 is the most common type associated with AIDS in the United States, Europe, and Central Africa, whereas HIV-2 causes a similar disease principally in West Africa and India. The ensuing discussion relates primarily to HIV-1, but is generally applicable to HIV-2 as well.
Structure of HIV
Similar to most retroviruses, the HIV-1 virion is spherical and contains an electron-dense, cone-shaped core surrounded by a lipid envelope derived from the host cell membrane (
Fig. 5.37 ). The virus core contains (1) the major capsid protein p24; (2) nucleocapsid protein p7/p9; (3) two copies of viral genomic RNA; and (4) the three viral enzymes (protease, reverse transcriptase, and integrase). p24 is the most abundant viral antigen and is the antigen detected by an assay widely used to diagnose HIV infection. The viral core is surrounded by a matrix protein called p17, which lies underneath the virion envelope. Studding the viral envelope are two viral glycoproteins, gp120 and gp41, which are critical for HIV infection of cells.
The HIV-1 RNA genome contains the gag, pol, and env genes, which are typical of retroviruses. The products of the gag and pol genes are large precursor proteins that are cleaved by the viral protease to yield the mature proteins. In addition to these three standard retroviral genes, HIV contains several accessory genes, including tat, rev, vif, nef, vpr, and vpu, which regulate the synthesis and assembly of infectious viral particles and the pathogenicity of the virus.
Molecular analysis of different HIV-1 isolates has revealed considerable variability in certain parts of the viral genome, mostly within sequences that encode particular regions of the envelope glycoproteins. Because the http://ebooksmedicine.net