Combination of Pre-Exposure and Postexposure Prophylaxes Used for an Occupational Exposure to HIV: A Case Report

Background: Pre-exposure prophylaxis (PrEP), the usage of antiretroviral medications in HIV-uninfected individuals to prevent acquisition of HIV, has been identied to be sucient and safe for HIV prevention. Case presentation: A surgeon was prescribed Tenofovir disoproxil fumarate (TDF) and emtricitabine (FTC) as pre-exposure prophylaxis before he performed a surgery for HIV positive patient. After occupational exposure, he was prescribed TDF/FTC and Raltegravir as postexposure prophylaxis. Serology conrmed no HIV infection at follow-ups. Conclusion: This brief report presents a case who received PrEP and PEP in an occupational exposure to indicate the feasibility of the use of PrEP in occupational exposure.


Background
Health care workers (HCWs) are at high risk of occupational exposure to many infections, such as human immunode ciency virus (HIV). The World Health Organization (WHO) estimated about 3 million occupational exposures in health care settings each year, 90% of which occurred in developing countries. HCWs working in the departments such as operating, delivery, emergency rooms and laboratories suffer from a higher risk of exposure 1 . It has been estimated that more than 250,000 HCWs were exposed to HIV each year and about 1,000 HIV infections were likely to happen 2 .
The advent of antiretroviral therapy (ART) has greatly improved the management and prevention of HIV infection 3 . Postexposure prophylaxis (PEP) has been proved to be a safe and effective treatment strategy aimed at preventing infection in those with recent HIV exposures. Approximately, 81% of the transmission of HIV risk can be reduced using PEP 4 . Based on the WHO guidelines, all the HCWs are required to use PEP after HIV occupational exposures 4 .
Pre-exposure prophylaxis (PrEP), the usage of antiretroviral medications in HIV-uninfected individuals to prevent acquisition of HIV, has been identi ed to be su cient and safe for HIV prevention through casecontrol, observational and randomized clinical trial data 5 . In 2014, WHO recommended PrEP as a critical part of comprehensive HIV prevention. In 2015, the use of PrEP was further expanded from men who have sex with men (MSM) to all HIV high-risk populations 6 . However, the use of PrEP in HIV occupational exposure has not been reported.
Herein, we described the rst reported use of combination of PrEP and PEP in a surgeon who was occupationally exposed to HIV during operation.

Case Presentation
Surgeon X, male, 31 years old, had planned to perform the open reduction and internal xation of calcaneal fracture for a HIV serological positive patient. The patient, a 45-year-old male worker, was taken to hospital after being injured on a construction site and diagnosed as a calcaneal fracture at 21 days before he come to Surgeon X for surgery. Preoperative laboratory ndings suggested that the patient had an HIV viral load of 27,524 copies/ml and CD4 positive T lymphocyte count was 344/dl. He stated that he had not ever received any antiviral treatment previously. Considering patient's old and complex fracture, the reduction procedures would be very di cult and the operation might take a long time with a requirement of numerous kirschner pin immobilization. Surgeon X assessed that there was a high probability of occupational exposure during the operation and a high risk of infection with HIV after occupational exposure. Based on his understanding of on-demand advancement of PrEP strategy in HIV prevention 7 , Surgeon X went to our department requesting the PrEP. He had last tested with negativity for HIV 2 weeks earlier, and had no other risk events in the preceding 3 months. He had received the Tenofovir disoproxil fumarate (TDF) and emtricitabine (FTC) treatment for post-exposure prophylaxis in the past (out of use at that moment) with no side effects. Therefore, it was unlikely that there would be any discomfort during the surgery. Surgeon X took a loading dose of 600 mg of TDF and 400 mg of FTC with food 2 hours before surgery. In case of discomfort or other unexpected circumstances during the operation, he invited another Surgeon of the same seniority as him as an extra assistant. The operation lasted 2.5 hours and he did not feel any discomfort during the operation. Unfortunately, towards the end of the operation, the temporary kirschner needle pricked his thumb. PEP then must be started. After rst aid, counseling and risk assessment, consent-based laboratory testing showed a baseline HIV antibody/antigen negative. Surgeon X was prescribed a course of TDF/ FTC and Raltegravir (RAL) for 28 days as PEP according to local guidelines 8 . Considering the the generated PrEP, he took only 400 mg of RAL and 12 h later another 400 mg of RAL at the rst day. 24 h after PrEP, Surgeon X began taking a dose of 300 mg of TDF and 200 mg of FTC once a day in combination with 400 mg of RAL twice a day as a PEP regimen. Serological tests showed that HIV infection had not occurred at 1-month and 3-month follow-up.

Discussion And Conclusions
In 2015, WHO updated the previous recommendations on PrEP and recommended PrEP to the individuals at substantial risk of acquiring HIV rather than limiting the recommendation to speci c populations.
Substantial risk of HIV infection is provisionally de ned as HIV incidence greater than 3 per 100 personyears in the absence of PrEP 6 . Moreover, this new recommendation also pointed out that individual risk varied with individual behaviors. Among some individuals, they actually stay at substantial risk who should be attracted to PrEP services in locations although the overall incidence of HIV infection is low. The thresholds for offering PrEP may vary depending on a variety of considerations, including available resources, the relative costs, feasibility and demand for PrEP. According to previous reports, Surgeon X's risk attributed to percutaneous injuries involving HIV was approximately 0.3% (95% CI, 0.2-0.5%) 9 . We estimated that Surgeon X's risk of HIV infection after occupational exposure could be higher than 0.3%, because the patient did not receive any antiviral treatment prior to surgery with a high viral load and greater chance of deep puncture during surgery 10 . As Surgeon X had a strong desire for PrEP, we prescribed TDF/ FTC for him as PrEP. The standard use of TDF/FTC as PrEP is 1 tablet (300 mg of TDF and 200 mg of FTC) per day, but studies on MSM showed that PrEP on demand (2 tablets taken 2-24 h before sex, and another pill taken 24 h and 48 h after the rst dose) could also effectively prevent HIV infection. The risk of infection can be reduced by 86.0% compared with the placebo group 7 . Therefore, we advised Surgeon X to take 2 tablets on-demand 2 h before surgery. Here we describe for the rst time the use of PrEP before occupational exposure. After the occurrence of occupational exposure, given the possibility of blocking failure of PrEP, which was reported by other researches 11 , PEP was still conducted timely. And the combination of PEP and PrEP ultimately ensured that Surgeon X was not infected with HIV after his occupational exposure. In the current case report, Surgeon X realized that he had suffered from occupational exposure during the surgery. and then the PEP was conducted after his immediate report. Thus, we can't predict whether Surgeon X can prevent HIV infection with PrEP alone after occupational exposure to HIV.
In clinical and laboratory settings, it is common for HCWs to be unaware of occupational exposure to HIV.
In this situation, PEP is always not conducted and HIV infection has been reported as a result 12 . Because the HIV vaccine development still has a long way to go, further evaluation is needed to determine whether PrEP can effectively block HIV transmission in this high-risk group. This retrospective study was approved by the ethics committee of Beijing Ditan Hospital, Capital Medical University. All procedures performed in studies involving human participants were in accordance with the ethical standards of the insti-tutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Consent for publication:
Written informed consent was obtained from the patient for publication of this case report and any accompanying images.
Availability of data and materials: The datasets used and/or analysed during the current study are available from the corresponding author on reasonable request.