Effect of short-course of antiretroviral agents on serum triglycerides of healthy individuals. Occupational exposure to HIV: experience at a tertiary care center. A case-control study of HIV seroconversion in health care workers after percutaneous exposure. Centers for Disease Control and Prevention Needlestick Surveillance Group. Tolerability and side-effects of post-exposure prophylaxis for HIV infection. Postexposure HIV prophylaxis regimen. Drug-induced aminotransferase alterations during antiretroviral HIV post-exposure prophylaxis.
nan We examined our hospital-based occupational health clinic's experience with combination antiretroviral therapy for postexposure prophylaxis for human immunodeficiency virus (HIV). Over a 12-month period, 68 workers started postexposure prophylaxis: 23 with zidovudine and lamivudine and 45 with zidovudine, lamivudine, and indinavir. Fifty-one (75%) of the 68 workers starting postexposure prophylaxis reported one or more side effects. Side effects were more common among those taking three drugs. Many workers failed to complete the recommended 28-day regimen because of the side effects of the various treatments. The estimated mean cost for evaluations, prophylaxis, and monitoring of exposed workers was $669 per reported exposure. In our experience, major challenges in carrying out the current HIV postexposure prophylaxis guidelines include expeditious source testing, improved staff education and prevention measures, and scrupulous monitoring of workers taking combination antiretroviral drugs for postexposure prophylaxis, with consideration of alternate regimens for intolerant workers. The average risk of human immunodeficiency virus (HIV) infection after percutaneous exposure to HIV-infected blood is 0.3 percent, but the factors that influence this risk are not well understood.
                We conducted a case-control study of health care workers with occupational, percutaneous exposure to HIV-infected blood. The case patients were those who became seropositive after exposure to HIV, as reported by national surveillance systems in France, Italy, the United Kingdom, and the United States. The controls were health care workers in a prospective surveillance project who were exposed to HIV but did not seroconvert.
                Logistic-regression analysis based on 33 case patients and 665 controls showed that significant risk factors for seroconversion were deep injury (odds ratio= 15; 95 percent confidence interval, 6.0 to 41), injury with a device that was visibly contaminated with the source patient's blood (odds ratio= 6.2; 95 percent confidence interval, 2.2 to 21), a procedure involving a needle placed in the source patient's artery or vein (odds ratio=4.3; 95 percent confidence interval, 1.7 to 12), and exposure to a source patient who died of the acquired immunodeficiency syndrome within two months afterward (odds ratio=5.6; 95 percent confidence interval, 2.0 to 16). The case patients were significantly less likely than the controls to have taken zidovudine after the exposure (odds ratio=0.19; 95 percent confidence interval, 0.06 to 0.52).
                The risk of HIV infection after percutaneous exposure increases with a larger volume of blood and, probably, a higher titer of HIV in the source patient's blood. Postexposure prophylaxis with zidovudine appears to be protective. A study of HIV post-exposure prophylaxis in 28 recipients showed that indinavir-containing regimens were poorly tolerated. This finding has implications for compliance and efficacy of the currently recommended combinations. nan In 655 individuals receiving HIV postexposure prophylaxis (PEP), drug-induced aminotransferase alterations were frequent and severe in the nevirapine-including regimen, rare and mild-to-moderate in other combinations, and always reversible. Grade 3-4 incidence in protease inhibitor or nevirapine PEP was 0.5 and 25.0 per 100 person-months, respectively. Apart from nevirapine, continuing PEP appears to be safe even in the case of aminotransferase alterations. The usefulness of routine monitoring of liver function during PEP could be re-considered.
The use of occupational PEP is based on limited direct evidence of effect. However, it is highly unlikely that a definitive placebo-controlled trial will ever be conducted, and, therefore, on the basis of results from a single case-control study, a four-week regimen of PEP should be initiated as soon as possible after exposure, depending on the risk of seroconversion. There is no direct evidence to support the use of multi-drug antiretroviral regimens following occupational exposure to HIV. However, due to the success of combination therapies in treating HIV-infected individuals, a combination of antiretroviral drugs should be used for PEP. Healthcare workers should be counseled about expected adverse events and the strategies for managing these. They should also be advised that PEP is not 100% effective in preventing HIV seroconversion. A randomized controlled clinical trial is neither ethical nor practical. Due to the low risk of HIV seroconversion, a very large sample size would be required to have enough power to show an effect. More rigorous evaluation of adverse events, especially in the developing world, are required. Seeing that current practice is partly based on results from individual primary animal studies, we recommend a formal systematic review of all relevant animal studies.