Hepatitis C Virus Post-Exposure Prophylaxis for Health Care Workers

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).