To Test or Not To Test

1. To Test or Not To Test Lisa Cornelius, MD, MPH Regional Medical Director DSHS HSR 7

2. DISCLOSURE STATEMENTConflict of Interest I have no real or perceived vested interests that relate to this presentation nor do I have any relationships with pharmaceutical companies, biomedical device manufacturers, and/or other corporations whose products or services are related to pertinent therapeutic areas

3. DISCLOSURE STATEMENT Commercial support There is no commercial company support for this CNE activity Non-Endorsement of Products The Center for Health Training approval status refers only to continuing nursing education activities and does not imply that there is a real or implied endorsement of any product, service, or company referred to in this activity nor of any company subsidizing costs related to the activity Off-Label Product Use This CNE activity does not include any unannounced information about off-label use of a product for a purpose other than that for which it was approved by the Food and Drug Administration (FDA)

4. LEARNING OBJECTIVES At the conclusion of this training, participants will be able to… Discuss the 2006 CDC Revised Recommendations for HIV Testing Recognize the benefits of implementing routine opt-out testing Explain the ethical issues related to routine HIV testing in medical settings

5. Since the first cases were diagnosed 30 years ago - • Over 576,000 Americans have lost their lives to AIDS • More than 56,000 people in the US become infected with HIV each year • There are more than 1.1 million Americans living with HIV – 1 in 5 (21%) are unaware of their infection • Almost half of all Americans know someone living with HIV

6. Protease inhibitors = HAART

8. Only compose 12% of US population

10. Only compose 12% of US population

11. Percent of Total HIV Diagnoses that were Late Diagnoses* by Race/Ethnicity and Sex, Texas 2009 *AIDS diagnosis occurred within 1 month of HIV diagnosis

12. AustinHSDA* - Living HIV/AIDS Cases - 2010 *Bastrop, Blanco, Burnet, Caldwell, Fayette, Hays, Lee, Llano, Travis, Williamson

13. Austin HSDA* - New HIV Cases - 2010 *Bastrop, Blanco, Burnet, Caldwell, Fayette, Hays, Lee, Llano, Travis, Williamson

14. Travis County HIV/AIDS Trends - 2010 3,791 Persons living with HIV/AIDS in Travis County through December 2010

15. Travis County Newly Reported HIV Cases – 2003 - 2010

16. Travis County New HIV Cases by Race/Ethnicity 2010 (N=197)

17. The Problem • Every 9 ½ minutes someone in the U.S. is infected with HIV • More than 20% of those living with HIV do not know it • Late diagnosis contributes to: • Poor outcomes, decreased productivity, and early death • Increased health care costs • More transmission of HIV

18. http://www.cdc.gov/mmwr/preview/mmwrhtml/mm5731a1.htm

19. 18.3 million http://www.cdc.gov/mmwr/preview/mmwrhtml/mm5502a9.htm?s_cid=mm5502a9_e

20. http://www.cdc.gov/mmwr/preview/mmwrhtml/ss5506a1.htm?s_cid=ss5506a1_ehttp://www.cdc.gov/mmwr/preview/mmwrhtml/ss5506a1.htm?s_cid=ss5506a1_e

21. http://www.cdc.gov/mmwr/preview/mmwrhtml/ss5506a1.htm?s_cid=ss5506a1_ehttp://www.cdc.gov/mmwr/preview/mmwrhtml/ss5506a1.htm?s_cid=ss5506a1_e

22. http://www.cdc.gov/hiv/topics/testing/resources/reports/pdf/ctr04.pdfhttp://www.cdc.gov/hiv/topics/testing/resources/reports/pdf/ctr04.pdf

23. The Facts • Persons who do not know they are infected with HIV may be responsible for more than half of new transmissions • Most of those unaware of their infection visit a health care facility but are not tested for HIV

24. Effect of Awareness on Transmission ~25% Unaware of Infection Accounts for ~54% of New Infections Marks, et al AIDS 2006;20:1447-50 ~75% Aware of Infection ~46% of New Infections People with HIV/AIDS: 1,039,000-1,185,000 New Sexual Infections Each Year: ~32,000

25. The Solution • Implement routine HIV testing in all health care settings per the 2006 CDC Recommendations MMWR 2006; 55 (RR14); 1-17 • Establishing early care for HIV positive patients results in better survival gains than chemotherapy (non-small cell lung cancer), adjuvant chemotherapy (breast cancer), acute myocardial infarction, and bone marrow transplant. Walensky et al. JID, 2006

27. Objectives of the 2006 Revised Recommendations • Increase HIV screening in health-care / medical settings. • Foster earlier detection of HIV infection • Identify and counsel persons with unrecognized HIV infection and link them to services • Further reduce perinatal HIV transmission

28. Revised RecommendationsAdults and Adolescents

29. Hall et al. J Acquir Immune Defic Syndr 2008;249:294-297

30. Revised RecommendationsAdults and Adolescents • When acute retroviral infection is a possibility, use an RNA test in conjunction with an HIV antibody test Development of symptoms typically coincides with high-level viremia and initial immunologic response in 40-90% around time of seroconversion at 2-6 weeks • Presence of seroconversion symptoms has been correlated with more-rapid disease progression Mandell Prin Pract Infect Dis 2000 Pincus CID 2003;37:1699-1704

31. Laboratory Testing Primary HIV infection Antibody may not have yet formed at the time of peak viremia and onset of symptoms: “window period” • Detectable viral load – typically very high • Often exceeds 1 million copies/ml • Low levels may be false positive – some suggest threshold of >5000 copies/ml to improve specificity • Negative or weakly positive EIA and • negative or evolving results on Western blot • VL not approved by FDA for diagnosis – thus need f/u Antibody EIA and WB for confirmation Kassutto CID 2004;38:1447-53

32. Laboratory Testing Time between HIV infection and positive HIV PCR: ECLIPSE PERIOD • is shorter than the “window period” (infection and HIV EIA+) • Still not short enough to prevent transmission • 40yo male adult-film actor in California underwent monthly VL testing by PCR • Neg Feb 2004 – Brazil for movie – flu-like illness 1 week before March 2004 testing (neg) ---April 2004 test + • Unprotected sexual contact with 13 females: 3+ • No cases among 2nd/3rd degree contacts MMWR 2005 sept 23;54:923-6.

33. Revised RecommendationsAdults and Adolescents • Include HIV consent with general consent for care - A separate signed informed consent should notbe required • Prevention counseling in conjunction with HIV screening in health care settings should not be required • Arrange access to care, prevention, and support services for patients with positive HIV test results

34. Results in the US • The $111 million effort provided funding for health departments in 25 of the nation’s hardest-hit areas • CDC-supported health departments were able to offer 2.8 million HIV tests in just three years • As a result of the Expanded Testing Initiative, more than 18,000 Americans living with HIV learned their HIV status for the first time • Approximately three-quarters of the individuals who were newly diagnosed were successfully linked to HIV care, of those for whom follow up data were available • Each HIV infection averted saves an estimated $367,000 in lifetime medical costs (2009 dollars) http://www.whitehouse.gov/blog/2011/06/27/national-hiv-testing-day-2011-0

35. Opt-out HIV testing in STD clinics 1999 Opt-out HIV testing pregnant women 1997 Results in Texas

36. Criteria that Justify Routine Screening • Serious health disorder that can be detected before symptoms develop • Treatment is more beneficial when begun before symptoms develop • Reliable, inexpensive, acceptable screening test • Costs of screening are reasonable in relation to anticipated benefits • Treatment must be accessible Principles and Practice of Screening for Disease -WHO Public Health Paper, 1968

37. Laboratory Testing • HIV antibody EIA: screening detects both HIV1 and HIV2 • Western Blot: confirmatory assay specific for HIV1 • p24 band often first to be detected • When present alone, test considered indeterminate • Also requires band against gp120/160 and band against gp41-43 Mandell Prin Pract Infect Dis 2000 Kassutto CID 2004;38:1447-53

38. Laboratory Testing • Rapid tests for HIV (Oraquick) • Performed on oral fluid and blood/serum • Approved FDA screening test • Results available in 20-40min • Sensitivity: 99.3% • Specificity: 99.8% Guidelines Aberg CID 2004;39: http://www.cdc.gov/hiv/pubs/rt/OraQuick_Test.gif http://www.cdc.gov/hiv/pubs/Unigold-kit.jpg

39. JID 2007; 195:425-31 Quantify the relative contribution of %CD4 to risk of disease progression in patients receiving ART

40. Probability of Developing AIDS Mellors, et al. Ann Int Med. 1997;126:946-954.

42. Benefits of Antiretroviral Therapy • CD4 <200 higher risk of opportunistic diseases, non-AIDS morbidity, and death • ART improves survival, delays disease progression • CD4 200-350 higher mortality rate, greater incidence Tb • CD4 350-500 higher rate of progression to AIDS and death • CD4 >500 higher mortality but limited data

43. Benefits of Routine Testing • Identify new HIV cases earlier • Early diagnosis and treatment leads to: • better prognosis, • greater response to therapy, • reduced viral load, • lower transmission of HIV by reducing the number of persons unaware of their HIV status and unknowingly transmitting the virus to partners, • slower clinical progression, and • reduced mortality

44. Missed Opportunities for HIV Diagnosis During 2001 to 2005 a total of 4,315 case of HIV infection were reported in S Carolina; 1,784 (42%) developed AIDS within 1 year of HIV test; 1,302 (73%) made 7,988 previous health-care visits(median 4 per patient) but were not tested for HIV MMWR December 1, 2006

45. Missed Opportunities for HIV Diagnosis Prospective study 499 patients presenting to urban urgent care center (Boston) with sx of a viral illness and any recent potential risk for HIV infection (>=1 of the following) • Sexual contact, IVDU, crack cocaine, ETOH use in prior 2 months • Tested for acute HIV using ELISA and RNA assays • Diagnosed 5 (1%) with acute HIV and 6 (1.2%) with chronic HIV • No false positives of RNA assay No signs or symptoms reliably distinguished patients with acute HIV from those who were HIV uninfected Mandell Prin Pract Infect Dis 2000 Pincus CID 2003;37:1699-1704

46. What’s the Point? • Reduce the number of new HIV infections • Reduce health disparities • Increase access to and use of HIV care and treatment

47. The ethical dilemma – To test or not to test? • What determines the ethical standards we follow? • What do we base our ethical standards on? • How do these standards get applied to specific situations, specifically to routine HIV testing?

48. Three common principles in bioethics • Respect for persons (autonomy) entails respecting the decisions of autonomous persons and protecting persons who lack decision-making capacity and therefore are not autonomous • also imposes an obligation to treat persons with respect by maintaining confidences and keeping promises • Beneficenceimposes a positive obligation to act in the best interests of patients • often is understood to require that the risks of research/treatment be minimized and that the risks be acceptable in light of the potential benefits • Justicerequires that people be treated fairly • often understood to require that benefits and burdens be distributed fairly within society http://hivinsite.ucsf.edu/InSite?page=kb-08-01-05#S2X

49. Other approaches of ethical standards • Utilitarian: Provides the most good or does the least harm, produces the greatest balance of good over harm for all • Common good: Life in community is a good in itself and our actions should contribute to that life • Interlocking relationships of society are the basis of ethical reason and that respect and compassion for all others-especially the vulnerable-are requirements for such reasoning • Virtue: Dispositions that enable us to act according to the highest potential of our character and on behalf of values like honesty, courage, compassion, generosity, tolerance, etc

50. Not everyone agrees on… • A standard behavior • The same set of human and civil rights • What is a ‘good’ and what is a ‘harm’ • How to answer “What is ethical?” • Population health vs individual health • Mandatory testing? • Costs of testing • Mandatory treatment?