Hepatitis C Virus Post-Exposure Prophylaxis for Health Care Workers
Hepatitis C Virus Post-Exposure Prophylaxis for Health Care Workers
To assess the safety and tolerability of the use of telaprevir in the setting of
 post-exposure prophylaxis among HCW exposed to HCV genotype 1 or genotype 2.

 To assess the election rate of postexposure prophylaxis for HCV-related occupational
 exposures in HCW.
At MGH and BWH, HCW exposed to blood or visibly bloody fluids are referred immediately to
 Occupational Health Services. The person whose blood or body fluid is the source of an
 occupational exposure should be evaluated for HBV, HCV, and HIV infection. Information
 available in the medical record at the time of exposure, or from the source person, might
 confirm or exclude bloodborne virus infection. If the HBV, HCV, and/or HIV infection status
 of the source is unknown, the source patient should be informed of the incident and tested
 for serologic evidence of bloodborne virus infection, including HBsAg, HCV antibody, and HIV
 antibody. Reactive results by EIA for anti-HCV are confirmed by HCV RNA PCR, which is tested
 using Roche COBAS TaqMan quantitative assay (Roche Molecular Systems) with a lower limit of
 quantitation of < 43 IU/ml. HCV RNA testing is performed twice weekly at MGH and BWH. In the
 event that the source patient's HCV antibody is positive and the HCV RNA is below the lower
 limit of detection, an HCV Recombinant Immunoblot Assay (RIBA) will be ordered: if the RIBA
 is negative, then the positive HCV antibody is interpreted as a false positive result, and
 the source patient is not infected with HCV. If the RIBA is positive, the source patient will
 then receive serial HCV RNA testing

 For HCW exposed to an HCV-positive source, HCV antibody testing is performed at the time of
 exposure. Per standard practices recommended by Partners Occupational Health Services, HCV
 RNA testing of HCW is not performed at the time of exposure, unless the HCV antibody test is
 positive. For the current study, if a HCW meets inclusion criteria (specifically, has an
 exposure through needlestick injury with a hollow-bore needle to a source patient who is
 anti-HCV(+) and HCV RNA (+); and the HCW is anti-HCV Ab negative) and is interested in
 enrolling in the study, HCV RNA testing of eligible HCW will be performed at the initial
 visit.

 For potential study enrollment, patients will be directly referred from Partners Occupational
 Health Services (BWH or MGH). They will be responsible for contacting study personnel by
 pager. In the event that the exposure occurs after the Occupational Health Services office is
 closed, the HCW will be evaluated in the Emergency Room as per standard protocol, and will be
 referred to study personnel the following business day. The HCW will then be screened with an
 interview in person, and patients with an appropriate exposure will be eligible for
 inclusion.

 Study drug will be offered to subjects who were exposed to potentially HCV-infected blood
 after needlestick injury with hollow-bore needles. Blood on intact skin is considered
 low-risk and, therefore, treatment will not be recommended. Other unusual injuries/exposures
 will be included on an individual basis by study physicians.

 Once the HCW signs informed consent to participate in the study, he/she will be offered a
 prescription for PEP with telaprevir 750 mg three times per day for 4 weeks within a five (5)
 day period from his/her exposure.

 Telaprevir has been shown to interact with both HIV protease inhibitors and reverse
 transcriptase inhibitors through their activity upon the CYP3A enzyme. With respect to the
 interactions between telaprevir and HIV protease inhibitors, it is not recommended to
 co-administer darunavir/ritonavir, fosamprenavir/ritonavir, or lopinavir/ritonavir with
 telaprevir[19]. In addition, regarding the use of reverse transcriptase inhibitors,
 concomitant administration of telaprevir and efavirenz resulted in reduced steady-state
 exposures to telaprevir and efavirenz. Van Heeswijk et al conducted three open-label,
 randomized cross-over trials among HIV and HCV negative healthy volunteers, and found that
 therapeutic levels of telaprevir, efavirenz, and tenofovir were maintained when the
 telaprevir dose was increased to 1250 mg three-times daily.

 As a result of these interactions, in cases where a HCW is exposed to HCV and HIV and elects
 to take HIV PEP, telaprevir will be offered for HCV PEP if one of the following HIV PEP
 regimens is prescribed:

 1. Tenofovir/Emtricitabine (Truvada) + Atazanavir/Ritonavir

 2. Tenofovir/Emtricitabine (Truvada) + Raltegravir

 All decisions regarding post-exposure prophylaxis for HCW exposed to HCV and HIV will be
 discussed with the HIV/ID fellow.

 Furthermore, for HCW who are HIV-infected and receiving HAART at the time of study
 enrollment, discussions will be held between the study team and the Infectious Disease
 specialist who is managing the HAART regimen of the HCW, in order to determine whether the
 patient could safely take telaprevir for HCV PEP.

 The HCW will have anti-HCV testing performed, along with stored serum for lookbacks if
 necessary, as is the current protocol in Occupational Health. In addition to the usual
 laboratories drawn by occupational health (HCV antibody at week 0, HCV RNA at weeks 4 and
 12), a blood count including differential will be required prior to consideration of study
 drug.

 At week 4, all enrolled patients will have quantitative HCV viral load testing (regardless of
 treatment election). If HCV RNA is detectable, HCW will be referred to GI/Hepatology for
 consideration of intensified antiviral therapy. If negative for patients in the treatment
 arm, then telaprevir will be discontinued at this time.

 At week 12 and 24, HCV RNA testing will be repeated. If positive, the patient will be
 referred for intensified antiviral therapy. Week 24 HCV RNA testing is necessary to look for
 the possibility that early prophylaxis with telaprevir delays the onset of hepatitis C
 infection.
Inclusion Criteria:

 -  MGH or BWH health care workers with exposure through needlestick injury with
 hollow-bore needles to source patients who are anti-HCV (+) and HCV RNA (+)

 -  HCW is anti-HCV Ab negative. HCW exposed through needlestick injury with hollow-bore
 needles to source patients who are anti-HCV (+) and HCV RNA (-), regardless of the
 RIBA result, will not be eligible for the study. In addition, efforts will be made to
 identify the source patient's genotype, and if the genotype is unknown, then genotype
 testing will be performed. If the genotype is 2 or 3, then the HCW exposed to the
 source patient will not be eligible for the study.

 -  HCW will be eligible if exposed to a source patient who has a genotype 1, or if the
 genotype of the source patient is unknown or unable to be ascertained

 Exclusion Criteria:

 -  Exposure to patient with known HCV genotype 2 or 3

 -  HCV Ab positive

 -  HCV Ab negative and HCV RNA > 1000 IU/ml

 -  Active malignancy

 -  Other condition in the opinion of the investigators or occupational health that makes
 telaprevir contraindicated in HCW

 -  Subjects with pre-existing end stage renal impairment or severe hepatic impairment
 (Child Pugh B or C), and anemia (starting hemoglobin 10 or less) will be excluded.

 -  Pregnant women will be excluded from the study. All female participants with
 reproductive potential will undergo a pregnancy test (specifically qualitative urine
 human chorionic gonadotropin), and those who test positive will not be eligible for
 study inclusion. Women whom are not pregnant and elect to enroll in the study will be
 advised that hormonal contraceptives may not be reliable during the study period and
 for up to two weeks following cessation of the study drug. During this time, female
 patients of childbearing potential should use two non-hormonal methods of effective
 birth control, examples of which include a male condom with spermicidal jelly OR
 female condom with spermicidal jelly (a combination of a male condom and a female
 condom is not suitable), a diaphragm with spermicidal jelly, a cervical cap with
 spermicidal jelly, or an intrauterine device (IUD).