To Test or Not To Test

Lisa Cornelius, MD, MPHRegional Medical Director

DSHS HSR 7

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

DISCLOSURE STATEMENTCommercial support

There is no commercial company support for this CNE activityNon-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 activityOff-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)

LEARNING OBJECTIVESAt 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

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

Protease inhibitors = HAART

Only compose 12% of US population

Only compose 12% of US population

Percent of Total HIV Diagnoses that were Late Diagnoses* by Race/Ethnicity and Sex, Texas

2009

23%

29%

20%22%

18%16%

0%

10%

20%

30%

40%

Black White Hispanic

Perc

ent (

%)

Male Female

*AIDS diagnosis occurred within 1 month of HIV diagnosis

Austin HSDA* - Living HIV/AIDS Cases - 2010

*Bastrop, Blanco, Burnet, Caldwell, Fayette, Hays, Lee, Llano, Travis, Williamson

Austin HSDA* - New HIV Cases - 2010

*Bastrop, Blanco, Burnet, Caldwell, Fayette, Hays, Lee, Llano, Travis, Williamson

Travis County HIV/AIDS Trends - 2010

3,791 Persons living with HIV/AIDS in Travis County through December 2010

Travis County Newly Reported HIV Cases – 2003 - 2010

202

194

227 225229

207

191197

170

180

190

200

210

220

230

240

2003 2004 2005 2006 2007 2008 2009 2010

91

4755

20

10

20

30

40

50

60

70

80

90

100

White African American Hispanic Other

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

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

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

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

18.3 million

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

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

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

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

Effect of Awareness on Transmission

~25% Unaware of

Infection

~75% Aware of Infection

People with HIV/AIDS: 1,039,000-1,185,000

New Sexual Infections Each Year: ~32,000

Accounts for ~54% of New

Infections

~46% of New

Infections

Marks, et alAIDS 2006;20:1447-50

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

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

Revised RecommendationsAdults and Adolescents

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

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 2000Pincus CID 2003;37:1699-1704

Laboratory TestingPrimary HIV infectionAntibody 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

Laboratory TestingTime 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.

Revised RecommendationsAdults and Adolescents

• Include HIV consent with general consent for care - A separate signed informed consent should not be 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

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

Results in Texas • Opt-out HIV testing in STD clinics 1999• Opt-out HIV testing pregnant women

1997

0

10

20

30

40

50

60

70

90 91 92 93 94 95 96 97 98 99 00 01 02 03 04 05 06 07 08 09

Year of Birth

No.

of P

erin

atal

ly In

fect

ed

Criteria that Justify Routine Screening1. Serious health disorder that can be

detected before symptoms develop2. Treatment is more beneficial when

begun before symptoms develop 3. Reliable, inexpensive, acceptable

screening test4. Costs of screening are reasonable in

relation to anticipated benefits5. Treatment must be accessible

Principles and Practice of Screening for Disease -WHO Public Health Paper, 1968

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 2000Kassutto CID 2004;38:1447-53

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.gifhttp://www.cdc.gov/hiv/pubs/Unigold-kit.jpg

JID 2007;195:425-31

Quantify therelative contributionof %CD4 to riskof disease progressionin patients receiving ART

Probability of Developing AIDS

Mellors, et al. Ann Int Med. 1997;126:946-954.

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

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

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

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 assayNo signs or symptoms reliably distinguished

patients with acute HIV from those who were HIV uninfected

Mandell Prin Pract Infect Dis 2000Pincus CID 2003;37:1699-1704

What’s the Point?• Reduce the number of new HIV infections

• Reduce health disparities

• Increase access to and use of HIV care and treatment

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?

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• Beneficence imposes 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

• Justice requires 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

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

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?

American Medical Association Opinion 2.23 – HIV Testing

• Physicians’ duties to promote patients’ welfare and to improve the public’s health are fostered by routinely testing their adult patients for HIV

• Physicians must balance these obligations with their concurrent duties to their individual patients’ best interest by the guidelines that follow:

AMA GuidelinesSupport routine universal routine universal opt-out

HIV screening to protect patients, avoid injury to third parties, and

promote public health (beneficience)Recommend/encourage patients to be screened the ethical tenets of respect for autonomy and informed

consent require that physicians continue to seek patients’ informed consent

It is justifiable to test patients without prior consent only in limited cases where the harms to individual autonomy are offset by significant benefits to known third parties. Such exceptions including testing for the protection of occupationally exposed health care professionals or patients.

Ensure HIV positive patients receive appropriate follow-up care and counseling (justice)

Comply with applicable disease reporting laws

Cheever CID 2007;44:1500-2

Case Studies