1. 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. 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. 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. 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. 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. 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. 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. 8 Targeted screening: Why not just assess risk behaviors? 10% to 25% of people testing positive report no risk behaviors 1 Prospective study 2 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. 9 Routine screening: Why not screen everyone? Potential disadvantages: » Medical harms: false-positive test result » Cost » Competing health care priorities

10. 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. 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. 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

13. Have at-risk patients been tested for HIV? Among at-risk patients, 36% had been tested for HIV

14. 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. 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. 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. 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

18. HIV Prevalence: Inpatients

19. HIV Prevalence: Outpatients

20. 20 Results: HIV Prevalence

21. 21 What is the Prevalence of HIV Among Older Patients? OutpatientInpatientOutpatientInpatient Age group 25-4411.4 (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) (total) HIV Prevalence (previously unknown)

22. 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. 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. 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. 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. 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 010 yrs8 yrs 10 years with moderate angina = 8 years with good health, or 8 “quality-adjusted” years of life.

27. 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. 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. 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. 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

31. Case Finding Only Screening and Case Finding Markov Model HIV Asymptomatic HIV Symptomatic AIDS UninfectedDeath HIV on HAART AIDS on HAART

32. 32 Costs Testing and counseling costs Cost of HAART Other medical costs of HIV care

33. Costs and Benefits of Screening

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

35. Lifetime costs and benefits, cost effectiveness, 1% Prevalence, ignoring transmission StrategyCostIncremental Cost QALYsIncremental QALYs CE $/QALY No Screening $51,517---18.626--- Screening$51,850$33318.6342.9 days$41,700

36. Lifetime costs and benefits, cost effectiveness, 1% prevalence, including transmission StrategyCostIncremental Cost QALYsIncremental QALYs CE $/QALY No Screening $52,623---18.576--- Screening$52,816$19418.5894.7 days$15,000

37. Effect of prevalence on cost effectiveness of screening

38. 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

39. Screening guidelines revisited

42. 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. 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. 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. 45 Summary Screening in the US provides substantial health benefit: » To the HIV+ individual » To the community – reduced transmission

46. 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

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

48. 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. 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. 51 Demographic Characteristics of At-risk Cohort

52. 52 Predictors of HIV Testing

53. 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. 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. 55 Treatment Model

56. 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. 57 Base-case population Prevalence = 1% Gender- and age-specific incidence

58. 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. 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. 60 Treatment assumptions Identified patients begin HAART when: » CD4 count = 350 cells/uL » Viral load = 4.6 log copies/mL HAART treatment: 1 st 2 nd 3 rd Virologic suppression, % 8065 30 2-yr virologic rebound, % 15x 2 x 2 Intolerance, % 25x 1 x 1.4

61. 61 What is the effect on HIV transmission? StrategyAnnual Transmission Rate MSMHeterosexual No screening2.80%2.09% One-time screening 2.22%1.66% Relative reduction 21%

62. 62 HIV Prevalence: Total

63. 63 Screening every 5 years can be cost effective, but depends on incidence

64. 64 Screening guidelines revisited Old CDC: 1% threshold » Too high USPSTF: recommends screening high risk Does not recommend for or against routine screening

65. 65 Predictors of HIV infection