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Background
Although failures of ZDV PEP have occurred (3), ZDV PEP was associated with a decrease of approximately 79% in the risk for HIV seroconversion after percutaneous exposure to HIV-infected blood in a case-control study among health-care workers (2). In a prospective trial in which ZDV was administered to HIV-infected pregnant women and their infants, a direct effect of ZDV prophylaxis on the fetus and/or infant may have contributed to the observed 67% reduction in perinatal HIV transmission (4); the protective effect of ZDV was only partly explained by reduction of the HIV titer in maternal blood (5). PEP also prevented or ameliorated retroviral infection in some studies in animals (6,7).
The average risk for HIV infection from all types of reported percutaneous exposures to HIV-infected blood is 0.3% (3). In the case-control study (2), risk was increased for exposures involving 1) a deep injury to the health-care worker, 2) visible blood on the device causing the injury, 3) a device previously placed in the source-patient's vein or artery (e.g., a needle used for phlebotomy), or 4) a source-patient who died as a result of acquired immunodeficiency syndrome (AIDS) within 60 days postexposure (and therefore was presumed to have a high titer of HIV) (2). Identification of these risk factors in the case-control study suggests that the risk for HIV infection exceeds 0.3% for percutaneous exposures involving a larger blood volume and/or higher HIV titer in blood. The risks after mucous membrane and skin exposures to HIV-infected blood (on average, approximately 0.1% and less than 0.1%, respectively {7}) probably also depend on volume of blood and titer of HIV. The risk is probably higher for skin contact that is prolonged, involves an area that is extensive or in which skin integrity is visibly compromised, and/or involves a higher HIV titer.
Although information about the potency and toxicity of antiretroviral drugs is available from studies of HIV-infected patients, it is uncertain to what extent this information can be applied to uninfected persons receiving PEP. In HIV-infected patients, combination therapy with the nucleosides ZDV and lamivudine (3TC) has greater antiretroviral activity than ZDV alone and is active against many ZDV-resistant HIV strains without significantly increased toxicity (8). Adding a protease inhibitor provides even greater increases in antiretroviral activity; among protease inhibitors, indinavir (IDV) is more potent than saquinavir at currently recommended doses and appears to have fewer drug interactions and short-term adverse effects than ritonavir (8). Few data exist to assess possible long-term (i.e., delayed) toxicity resulting from use of these drugs in persons not infected with HIV.
In currently recommended doses, ZDV PEP usually is tolerated
well by health-care workers; short-term toxicity associated with
higher doses primarily includes gastrointestinal symptoms, fatigue,
and headache (3,7). The toxicity of other antiretroviral drugs in
persons not infected with HIV has not been well characterized. In
HIV-infected adults, 3TC can cause gastrointestinal symptoms and,
in rare instances, pancreatitis. IDV toxicity includes
gastrointestinal symptoms and, usually after prolonged use, mild
hyperbilirubinemia (10%) and kidney stones (4%); the latter may be
limited by drinking at least 48 oz (1.5 L) of fluid per 24-hour
period (8). During the first 4 weeks of IDV therapy, the reported
incidence of kidney stones was 0.8% (Merck Research Laboratories,
unpublished data, 1996). As stated in the package insert, the
concurrent use of IDV and certain other drugs, including some
nonsedating antihistamines, is contraindicated. Based on limited
data, ZDV use in the second and third trimesters of pregnancy and
early infancy was not associated with serious adverse effects in
mothers or infants (4,9); data are limited regarding the safety of
ZDV during the first trimester of pregnancy or of other
antiretroviral agents during pregnancy. Although 3TC has been
associated with pancreatitis in HIV-infected children (8), whether
3TC causes fetal toxicity is unknown.
Source: The Centers for Disease Control and Prevention
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