Bruce A. Luxon, MD, PhD, FACG Consultant: Vertex Speakers Bureau: Merck Bruce A. Luxon, MD, Ph.D. Anton and Margaret Fuisz Chair in Medicine Professor and Chair Department of Medicine Georgetown University 1
Patient is a 28 year old male presenting with malaise, muscle aches, joint pain Past medical history really non-contributory High risk sexual behavior multiple partners New tattoos several over the past 9 months Question of IVDA in past 6 months Exam: Nervous, anxious white male, arrived 30 minutes late for appointment, keeps checking watch 3 After you suggest he needs screening blood work for HCV, HBV and HIV, he says he does not have time to wait for lab to draw blood. What are your options??? Insist he wait the 45 minutes for a lab opening Return to an outside lab at his convenience with your lab slip Re-emphasize how important the blood work and potential diseases (infections) are to his overall health Give up 4 2
History of HCV testing Early tests Currently available tests Why are point of care (POC) tests useful? Financial Patient compliance Screening high risk patients Recently developed rapid tests Description of tests Methodology Accuracy Cost 5 First reported cases of nona-nonb hepatitis reported in narcotic addicts in the 1950 s. Later testing showed that of 30 episodes of acute viral hepatitis 16 were not due to HAV, HBC, EBV or CMV. In 1970 s post transfusion hepatitis was relatively common in cardiac patients (one study: 11% of patients who received more than 4 units during surgery). 6 3
Late 1970 s major breakthrough: human sera could infect chimpanzees. Infectivity model showed that this was a small virus, with an envelope and that it was probably an RNA virus. In 1980 s cdna expression library was constructed by Choo et al at Chiron. One million clones were tested against sera from patients and infected chimps. One antigen was found to cross react: C110-3. 7 Science, 1989 Infected chimp Non-Infected chimp Non-Infected chimp 8 4
First generation ELISA test developed to detect antibody to C100-3 in patients: Hepatitis C now identifiable. Blood banks begin screening for HCV antibody (1990, FDA mandate). Second and third generation ELISA tests developed (1992). Other antigens found which promote antibodies and RIBA test developed (1992). 1993: First PCR HCV test is introduced outside of the United States. 9 1995: Two PCR kits (HIV and HCV), the first standardized "quantitative" PCR kits, launch outside of the United States. 1999: U.S. blood centers implement nucleic acid technology (NAT) testing for HCV and HIV, under an Investigational New Drug (IND) application. 2001: FDA approves two PCR-based HCV tests Testing for HCV virus clearance became standard of care while treating HCV infected patients. 10 5
Hepatology 2012 11 12 6
Touted by manufacturers but relatively sparse data Higher number of patients willing to be screened Cheaper cost to identify infected individuals Better compliance with counseling re infectivity Better compliance regarding treatment follow-up Better patient satisfaction Better health provider satisfaction 13 Considerable data exist that point of care testing for STD s helps with: Patient education Early initiation of patient treatment Probable reduced spread or STD to family members Data is less clear for HCV testing New York City Dept of Health provided free screening to high risk individuals through community based organizations (CBO) Drobnik, Am J Public Health, 2011 14 7
CBO s provided HIV testing, education and referrals for high risk population HCV test used rapid oral swab test Testing device swabbed along top and bottom gums Put in developing solution Results ready in 20 minutes Positive test shows results line; control also shown Standard blood testing also offered Clinic staff surveyed for Compliance with blood draws Ease of test explanation Ease of patient tracking Ease of phlebotomy Drobnik, Am J Public Health, 2011 15 Oral swab test agreed 100% with blood tests Increased volume of testing (35%) for oral swab versus blood test alone Testing took place in non-clinical setting (mobile van) Fear that blood would be used for other purposes Inability of staff to adequately draw blood Counseling about need to follow-up and ability to get return appointment increased 75%. Phlebotomist perceived diminished risk of needle stick. Drobnik, Am J Public Health, 2011 16 8
17 Steps in a typical blood sample test No antibody to HCV detected Has positive control but negative test 18 9
This test shows antibody to HCV. Positive control means test done properly. 19 An example of a triple test kit HBV HIV HCV Patient has antibody to HIV 20 10
Does it matter which source of body fluid is used? OraQuick single test data Lee, J Viol Meth, 2011 21 Lee, J Viol Meth, 2011 22 11
23 CDC: 1100 stored sera from IVDA abusers from 1997-99. About half were anti-hcv positive (half were negative). Gold standards were RIBA and third generation ELISA. Smith, JID, 2011 24 12
Meta analysis of 19 studies encompassing ~12,000 patients tested by various products Gold standards were good Accuracy of test was only determinant of study: no patient care issues addressed Shivkumar, Annals, 2012 25 26 13
Very hard to find cost information I tried CDC, NIH, FDA websites I tried Google for rapid HCV cost I tried CVS and Walgreen Finally in desperation I tried EBAY Amazon Found it 27 28 14
Costs run between $19 and $65 in a very unscientific survey Oral test tends to run higher Multiple tests (HIV, HBV, HCV) tend to run highest Most kits contain information on HCV as well as what to do for follow-up Cheaper kits tended to have more scanty information 29 Hepatitis C is an increasing problem, especially in the under-insured. Point of care testing has been shown to be beneficial in increasing compliance, patient education and both provider and patient satisfaction. Rapid HCV tests are available Blood, serum, saliva Multiple antibodies can be tested at the same time ~ HCV, HIV, HBV Rapid HCV tests are extremely accurate: both sensitivity and specificity are excellent (>98%). 30 15
We don t have any rapid testing available in ID clinic at Georgetown where I practice. We do have a blood draw station in clinic: waiting time 2-3 minutes but tests are sent out. Patient waited to get blood drawn, then left without making appointment to follow up. He is HCV GT1b, HIV (-), HbsAg (-) He has not responded to repeat phone calls or letter to make an appointment. 31 He may not be ideal candidate for treatment but one wonders if we could have engaged him with facts rather than speculation at the time of his initial clinic visit. CDC recommendation about universal screening of baby boomers will also require follow-up and appropriate access to health care once screened. 32 16