The Case for Routine Screening for HIV

Douglas K. Owens, MD, MS

VA Palo Alto Health Care System, Palo Alto, CA USA

Stanford University, Stanford CA, USA

June 2007

Supported by the Department of Veterans Affairs, the VA HIV QUERI, and the National Institute on Drug

Abuse

2

Should voluntary HIV screening be expanded in the U.S?

• Background

• Burden of HIV in health-care settings»Are at risk patients being tested?

»What is the prevalence of undocumented HIV disease?

• What are the costs and benefits of HIV screening?»Benefit to a person identified as having HIV

»Benefit from reduced transmission of HIV

3

Identification early in the course of HIV disease is critically important

• Access to highly active anti-retroviral treatment (HAART)

• Prophylaxis for opportunistic infections

• Counseling to reduce HIV transmission

4

But, HIV infection is often diagnosed late in the course of disease

• CDC Surveillance: 41% of patients develop AIDS within a year of diagnosis with HIV

• VA: 40% have CD4 count < 200 at diagnosis

• Up to 20,000 new infections in the U.S from people unaware they are infected (CDC)

The system for detecting HIV in the U.S. is inadequate

5

CDC and US Preventive Service Task Force Recommend Screening

• CDC, prior to September 2006: » Assess risk behaviors; screen high risk

» Routine voluntary screening if prevalence is 1% or greater

• CDC, current» Routine screening all health care settings (prevalence over 0.1%)

• USPSTF: Screen high risk people and pregnant women» Consider prevalence in determining policy

6

Two approaches to screening: targeted or routine screening

• Targeted screening: assess risk behaviors, screen if high risk» MSM» IDU» Multiple partners» Exchange sex for money or drugs or have partners who do» Past or present partners HIV-infected, bisexual, or IDU» History of STD» Blood transfusion between 1978-1985» Requests testing

7

Routine screening offers screening to all people in a specified clinical setting

• Defined by type of setting» STD clinics

»Homeless shelters

» TB clinics

»Clinics serving MSM

• Defined by prevalence»CDC: 1% prevalence (early 90’s)

8

Targeted screening: Why not just assess risk behaviors?

• 10% to 25% of people testing positive report no risk behaviors1

• Prospective study2 in STD clinic: testing only those with reported risk behaviors missed 75% of HIV diagnoses

• Risk assessment likely less reliable in high risk populations

1Chou et al, Ann Intern Med 2005; 143:55-73; 2Chen et al. Sex Trans Dis 1998; 25:539-43

9

Routine screening: Why not screen everyone?

• Potential disadvantages:»Medical harms: false-positive test result

»Cost

»Competing health care priorities

10

Summary: We are failing to identify people with HIV early in disease.

• They lose opportunity for maximum benefit from ARV

• Increased ongoing transmission

• Targeted or routine screening?

11

Should voluntary HIV screening be expanded in the U.S?

• Background

• Burden of HIV in health-care settings»Are at risk patients being tested?

»What is the prevalence of undocumented HIV disease?

• What are the costs and benefits of HIV screening?»Benefit to a person identified as having HIV

»Benefit from reduced transmission of HIV

12

Are at risk patients being tested?

• Used VA National Patient Care database to identify cohort seen at 4 VA medical centers from October 1, 1998 to September 30, 1999

• At risk defined as documentation of ICD9 codes for substance use, STD or hepatitis

• HIV testing information from October 1, 1995 to September 30, 2000 obtained for cohort

Have at-risk patients been tested for HIV?

0%

10%

20%

30%

40%

50%

60%

70%

80%

90%

100%

Site 1 Site 2 Site 3 Site 4 Multi-siteVA Healthcare System

Per

cen

t Not tested

Tested

Positive

Among at-risk patients, 36% had been tested for HIV

14

Are primary care patients at risk?

• Randomized trial of screening in primary care

• Reviewed charts of 750 UNTESTED patients

• 25% had HIV risk behaviors

• Of patients with risk behaviors, only 15% had risk assessment

Many patients were at risk, few had risk assessment, none were tested.

15

Should voluntary HIV screening be expanded in the U.S?

• Background

• Burden of HIV in health-care settings»Are at risk patients being tested?

»What is the prevalence of undocumented HIV disease?

• What are the costs and benefits of HIV screening?»Benefit to a person identified as having HIV

»Benefit from reduced transmission of HIV

16

The prevalence of HIV infection determines the yield of screening.

• Prevalence of unknown HIV infection is the critical determinant of yield of screening

• Total prevalence may be a reasonable marker for prevalence of unknown HIV infection

17

A blinded serologic survey can determine the prevalence of undocumented HIV infection

• Blinded, anonymous serologic survey

• Randomly sampled age-stratified blood specimens drawn for other purposes

• Unique patient specimens for inpatients and outpatients

• Collected data on demographics, comorbid conditions and prior HIV status

• HIV testing done using standard testing protocols after removing all identifiers

HIV Prevalence: Inpatients

0

1

2

3

4

5

6

7

8

9

10

Site A Site B Site C Site D Site E Site F

Site

Per

cen

t

HIV prevalence

Undocumented prevalence

HIV Prevalence: Outpatients

0

1

2

3

4

5

6

7

8

9

10

Site A Site B Site C Site D Site E Site F

Site

Per

cen

tHIV prevalence

Undocumented prevalence

20

Results: HIV Prevalence

Site 1 Site 2 Site 3 Site 4 Site 5 Site 6

HIV PrevalenceInpatient 1.20% 4.40% 3.00% 6.91% 2.40% 0.79%Outpatient 2.27% 4.13% 8.00% 8.93% 1.60% 0.93%Total 1.73% 4.26% 4.70% 7.97% 2.00% 0.87%

Undocumented PrevalenceInpatient 0.00% 0.14% 0.00% 1.70% 1.08% 0.16%Outpatient 0.27% 0.28% 0.29% 2.89% 0.67% 0.13%Total 0.14% 0.21% 0.15% 2.33% 0.88% 0.15%

Proportion Unidentified 0.08 0.05 0.03 0.29 0.44 0.17Prevalence

21

What is the Prevalence of HIV Among Older Patients?

Outpatient Inpatient Outpatient InpatientAge group 25-44 11.4 (9.3-13.7) 5.9 (4.2-8.1) 1.6 (0.8-2.7) 0.8 (0.3-2.0) 45-54 5.6 (4.4-7.2) 5.2 (4.0-6.6) 0.9 (0.4-1.6) 0.6 (0.3-1.3) 55-64 3.5 (2.3-5.2) 2.8 (1.7-4.3) 0.7 (0.2-1.7) 0.9 (0.3-1.9) 65-74 0.8 (0.4-1.6) 1.3 (0.6-2.3) 0.5 (0.2-1.2) 0.4 (0.1-1.0) >= 75 0.1 (0.0-0.6) 0.2 (0.0-0.9) 0.1 (0.0-0.6) 0.0 (0.0-0.4)

HIV Prevalence

% (95% CI) % (95% CI)(total)

HIV Prevalence (previously unknown)

22

Lessons from the serologic survey

• HIV prevalence at all our sites was substantially higher than the 0.1% prevalence recommended for routine screening by CDC currently

• From 3% to 44% of HIV infections were undocumented and probably unknown.

23

Providers aren’t aware their patients are at risk.

• Providers felt testing was not a high priority» Population not at risk

• One quarter of primary care patients DID have risk behaviors, none were tested

24

Should voluntary HIV screening be expanded in the U.S?

• Background

• Burden of HIV in health-care settings»Are at risk patients being tested?

»What is the prevalence of undocumented HIV disease?

• What are the costs and benefits of HIV screening?»Benefit to a person identified as having HIV

»Benefit from reduced transmission of HIV

25

Cost effectiveness analysis

• Compares two or more strategies

• Assesses the incremental benefit and incremental cost of one strategy versus another

• Calculate the incremental cost-effectiveness ratio:

Costs with screening – Costs without screening

Benefits with screening – Benefits without screening

26

Measuring health outcomes: the quality-adjusted life years (QALYs)

Time spent in a reduced state of health is equivalent to some shorter period of time in good health.

Moderate angina

No angina

0 10 yrs8 yrs

10 years with moderate angina = 8 years with good health, or 8 “quality-adjusted” years of life.

27

Interpreting the incremental cost-effectiveness ratio

• Less than $50,000 per QALY gained – usually considered good value

• $50,000 to $100,000 per QALY gained – sometimes considered good value

• Greater than $100,000 per QALY gained – often considered expensive

28

We evaluated the costs and benefits of screening*

• Potential benefits» For HIV+: increased length and quality of life

» For community: decreased transmission

• Costs» Screening and counseling costs

»Costs of treatment (HAART, prophylaxis for opportunistic infections)

* Sanders et al. NEJM 2005; 352:570-85

29

Screening strategies

• No screening» Testing for HIV only from case finding for

symptomatic patients

• HIV screening» Symptom-based case finding AND

»One-time or recurrent screening

30

Methods: A mathematical model of screening

• Mathematical model (Markov model) follows screened and unscreened cohort

• Perspective: societal

• Time horizon: lifetime

• Health benefit: quality-adjusted years

• Costs: U.S. testing and treatment costs

Case Finding Only

Screening andCase Finding

Markov Model

HIVAsymptomatic

HIVSymptomatic

AIDS

Uninfected

Death

HIVon HAART

AIDSon HAART

32

Costs

• Testing and counseling costs

• Cost of HAART

• Other medical costs of HIV care

Costs and Benefits of Screening

What is the benefit to the person identified as having HIV?

0

0.2

0.4

0.6

0.8

1

1.2

1.4

1.6

1.8

2

30 40 50 60 70 80 90

Age, years

Incr

ease

in L

ife

Exp

ecta

ncy

Du

e to

S

cree

nin

g, y

ears

Life Expectancy Quality Adjusted Life Expectancy

Lifetime costs and benefits, cost effectiveness, 1% Prevalence, ignoring transmission

Strategy Cost Incremental Cost

QALYs Incremental QALYs

CE

$/QALY

No Screening

$51,517 --- 18.626 ---

Screening $51,850 $333 18.634 2.9 days $41,700

Lifetime costs and benefits, cost effectiveness, 1% prevalence, including transmission

Strategy Cost Incremental Cost

QALYs Incremental QALYs

CE

$/QALY

No Screening

$52,623 --- 18.576 ---

Screening $52,816 $194 18.589 4.7 days $15,000

0

20,000

40,000

60,000

80,000

100,000

120,000

140,000

160,000

180,000

200,000

0.0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1.0

Prevalence (%)

Incr

emen

tal C

ost

Eff

ecti

vene

ss o

f Sc

reen

ing

($/Q

AL

Y)

Transmission Included No Transmission

Effect of prevalence on cost effectiveness of screening

38

Screening is cost effective even at low prevalence

• Including transmission, screening is cost effective when prevalence is above 0.05%

• Implication: screening is cost effective in all sites we surveyed, and likely in all but the lowest risk health-care settings

Screening guidelines revisited

42

Evidence for routine screening is compelling, but how should it be done?

• Addressed in a HIV QUERI randomized control trial»Doctor initiated, traditional testing and counseling

»Nurse initiated, traditional testing and counseling

»Nurse initiated, streamlined counseling, rapid testing

• Conducted by Steve Asch, Henry Anaya, Matt Goetz, and colleagues from the HIV QUERI

43

Nurse-based screening with rapid testing and counseling out performs other strategies

MD, traditional

Nurse, traditional

Nurse, streamlined counseling, rapid testing

% Tested % Received Result

40% 15%

85% 31%

89% 80%

44

Summary

• With our current approach to identification of HIV, almost half of people identified late in disease

• Many at-risk patients are seen in health-care settings

• Many are NOT tested

45

Summary

• Screening in the US provides substantial health benefit:» To the HIV+ individual

» To the community – reduced transmission

46

HIV Screening programs should be expanded in the U.S

• Screening is cost effective at a prevalence 20 times lower than that previously recommended by the CDC

• Routine screening would be cost effective in most health-care settings

• CDC guidelines for screening in the U.S now recommend screening in all health care settings

Thanks to the VA HIV Quality Enhancment Research Initiative (QUERI)

In collaboration with...VA Palo Alto/Stanford: Gillian Sanders, Ahmed Bayoumi, Vandana Sundaram, S. Pinar Bilir,

Christopher P. Neukermans, Chara E. Rydzak, Lena Douglass, Patricia Tempio, Dan Margolis, Laura Lazzeroni, and Mark Holodniy

VA San Francisco/UCSF: Peter Jensen, Vera Shadle, Diane Gyuricza

VA San Diego/UCSD:Valerie C. McWhorter, Teodora Agoncillo, Paula Paulk, Sam Bozzette

VA New York: Noreen Haren, Mark Tuen, Anne Dwyer, Mike Simberkoff

VA Greater Los Angeles/UCLA: Steve Asch, Henry Anaya, Matthew Goetz

VA New England: Allen Gifford

VA Memphis: Dennis Dietzen

VA North Chicago: Jill Nyland, Walid Khayr

49

References

• US Preventive Services Task Force. Screening for HIV: Recommendation Statement. Ann Intern Med 2005; 143:32-37.

• Chou et. al., Screening for HIV: A review of the evidence for the US Preventive Services Task Force. Ann Intern Med 2005; 143:55-73.

• Chou et. al., Prenatal Screening for HIV: A review of the evidence for the US Preventive Services Task Force. Ann Intern Med 2005; 143:38-54.

• Sanders GD, et. al., Cost effectiveness of screening for HIV in the era of highly active antiretroviral therapy. N Engl J Med 2005; 352:570-85.

• Paltiel AD, et. al., Expanded screening for HIV in the United States—an analysis of cost effectiveness. N Engl J Med 2005; 352:586-95.

51

Demographic Characteristics of At-risk Cohort

Site 1 Site 2 Site 3 Site 4 Multi-site n=4239 n=3016 n=3227 n=3192 n=317

Male 97% 98% 97% 98% 97%

Mean age 51 (23-92) 51 (21-91) 49 (20-87) 50 (22-94) 48 (27-76)

White 52% 41% 55% 30% 50%Black 14% 22% 13% 33% 36%Hispanic 8% 4% 6% 13% 7%Asian 1% 1% 1% <1% 2%Am. Indian 1% <1% 1% <1% 0Unknown 25% 31% 25% 24% 6%

52

Predictors of HIV Testing

Risk factor adj OR 95% CI

30-39 vs > 70 years 4.7 3.7-5.9

Black vs. White 1.21 1.1-1.34

Hispanic vs. White 1.17 1.01-1.3

Hepatitis C 2.39 2.16-2.67

Hepatitis B 1.83 1.36-2.47

Hepatitis B & C vs. neither 2.5 1.9-3.18

Cocaine Use 1.6 1.4-1.8

Opiate Use 1.6 1.4-1.8

STD 1.6 1.3-1.9

53

Logistic regression model

• Outcome: HIV infection

• Predictors included in the model were» Age» Race/Ethnicity» Site» Patient group: Inpatient/Outpatient» Hepatitis C» Hepatitis B» Comorbid conditions: Alzheimer’s, Liver disease, COPD, Pneumonia,

Septicemia, Malignant Neoplasms, STDs, Psychiatric conditions, Heart disease, CVD, Diabetes

54

HIV screening program description

• Voluntary

• Informed consent, pre- and post-test counseling

• Healthcare settings

• Counseling to reduce risk behaviors

• Referral to comprehensive care including HAART

55

Intolerance

Inefficacy

Non-Suppressive Therapy

Suppressive Therapy

AlternativeFirst

Regimen (2)

AlternativeFirst

Regimen (1)

AlternativeSecond

Regimen

FirstRegimen

SecondRegimen

ThirdRegimen

AlternativeFirst

Regimen (2)

AlternativeFirst

Regimen (1)

AlternativeSecond

Regimen

AlternativeFirst

Regimen (1)

AlternativeSecond

Regimen

FirstRegimen

SecondRegimen

ThirdRegimen

FirstRegimen

SecondRegimen

ThirdRegimen

SecondRegimen

ThirdRegimen

Treatment Model

56

Model description

• Health states were characterized by»Whether HIV was identified»Disease state (HIV or AIDS)»Antiretroviral therapy (suppressive or non-suppressive

therapy)»Viral load and CD4 count

• Rates of progression from HIV to AIDS and AIDS to death dependent on CD4 and viral load

57

Base-case population

• Prevalence = 1%

• Gender- and age-specific incidence

0.E+00

2.E-04

4.E-04

6.E-04

8.E-04

0 20 40 60 80

Age

Ann

ual I

ncid

ence

0.E+00

2.E-04

4.E-04

6.E-04

8.E-04

0 20 40 60 80

AgeA

nnua

l Inc

iden

ce

58

Sexual transmission of HIV

• Depended on:»Number of sexual partners at risk

» Type of sexual acts

»HIV+ person’s viral load– 1 log increase in viral load increased HIV transmission by

2.45 times

59

Effect of knowledge of HIV status

• Identified person reduces risk behavior

• Partners of identified HIV+ person will also be identified and begin treatment when appropriate

• Partner of unidentified HIV+ person identified through symptom-based case finding

60

Treatment assumptions

• Identified patients begin HAART when:» CD4 count = 350 cells/uL

» Viral load = 4.6 log copies/mL

• HAART treatment:

1st 2nd 3rd

Virologic suppression, % 80 65 30

2-yr virologic rebound, % 15 x 2 x 2

Intolerance, % 25 x 1 x 1.4

61

What is the effect on HIV transmission?

Strategy Annual Transmission Rate

MSM Heterosexual

No screening 2.80% 2.09%

One-time screening

2.22% 1.66%

Relative reduction

21% 21%

62

HIV Prevalence: Total

0

1

2

3

4

5

6

7

8

9

10

Site A Site B Site C Site D Site E Site F

Site

Per

cen

t

HIV prevalence

Undocumented prevalence

63

Screening every 5 years can be cost effective, but depends on incidence

0

20,000

40,000

60,000

80,000

100,000

120,000

140,000

160,000

180,000

200,000

One-time screening 5-yr 3-yr Annual

Screening Frequency

Incr

emen

tal C

ost

Eff

ecti

ven

ess

of

Rec

urr

ent

Scr

een

ing

($/Q

AL

Y)

Baseline Incidence 2x Incidence 3x Incidence

64

Screening guidelines revisited

• Old CDC: 1% threshold» Too high

• USPSTF: recommends screening high risk

• Does not recommend for or against routine screening

65

Predictors of HIV infection

Risk factor adj OR 95% CI

Age (increasing risk with lower age) -- p<0.01Site -- p<0.01Inpatient vs. Outpatient 0.72 0.56-0.93Black vs. White 1.83 1.38-2.43History of Hepatitis C 1.89 1.40-2.55History of Hepatitis B 1.76 1.05-2.95History of Pneumonia 4.83 3.39-6.88History of STD 6.07 4.23-8.72