Abstract: Effect of PEP on HIV seroconversion  No randomized controlled trials were identified. Only one case-control study was included. HIV transmission was significantly associated with deep injury (OR 15, 95% CI 6.0 to 41), visible blood on the device (OR 6.2, 95% CI 2.2 to 21), procedures involving a needle placed in the source patient's blood vessel (OR 4.3, 95% CI 1.7 to 12), and terminal illness in the source patient (OR 5.6, 95% CI 2.0 to 16). After controlling for these risk factors, no differences were detected in the rates at which cases and controls were offered post-exposure prophylaxis with zidovudine. However, cases had significantly lower odds of having taken zidovudine after exposure compared to controls (OR 0.19, 95%CI 0.06 to 0.52). No studies were found that evaluated the effect of two or more antiretroviral drugs for occupational PEP. Adherence to and complications with PEP  Eight reports from observational comparative studies confirmed findings that adverse events were higher with a three-drug regimen, especially one containing indinavir. However, discontinuation rates were not significantly different. 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.

Plain-language summary: This review evaluated the effects of antiretroviral post-exposure prophylaxis (PEP) for preventing HIV infection following occupational exposure. No randomized controlled trials were identified. Only one case-control study provides evidence for using zidovudine monotherapy. The study found that, in the occupational setting, HIV transmission was significantly associated with deep injury, visible blood on the sharp instrument, procedures involving a needle placed in the source patient's blood vessel, and terminal illness in the source patient. After taking these into account, it was found that those who became infected with HIV had significantly lower odds of having taken zidovudine after exposure, compared to those who did not seroconvert. 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 drugs should be used for PEP. Eight reports from other studies confirmed the findings that adverse events were higher with a three-drug regimen; however, discontinuation rates were not significantly different. A four-week regimen of post-exposure prophylaxis should be initiated as soon as possible after exposure, depending on the risk of seroconversion. Healthcare workers should be counseled about expected adverse events and given strategies for managing these events. They should also be advised that PEP is not 100% effective in preventing HIV seroconversion.