1. HIV Surveillance Case Definition Position Statement #12-ID-05 Overview CSTE Meeting June 3, 2012 Omaha, Nebraska Eve D. Mokotoff

2.  New HIV testing algorithms  New: criteria for a suspect case  HIV-2 infection  Stage 0 HIV infection  AIDS-defining conditions (opportunistic illnesses)  CD4 test results for staging for adults/adolescents  HIV Case definition for children  Physician-documented diagnosis- PDD (clinical, rather than laboratory criteria for a confirmed case)  PDD - date of diagnosis Proposed Revisions

3.  New HIV testing algorithms  New: criteria for a suspect case  HIV-2 infection  Stage 0 HIV infection  AIDS-defining conditions (opportunistic illnesses)  CD4 test results for staging for adults/adolescents  HIV Case definition for children  Physician-documented diagnosis- PDD (clinical, rather than laboratory criteria for a confirmed case)  PDD - date of diagnosis Proposed Revisions

4.  HIV cases should include persons with positive conclusions from any testing algorithm recommended by Criteria for Laboratory Testing and Diagnosis of Human Immunodeficiency Virus Infection: Approved Guideline, [CLSI document M53- A, ISBN 1-56238-758-8], published June 2011 by Clinical and Laboratory Standards Institute  Cases based on a presumptive positive result of a CLSI algorithm should not be distinguished from cases based on a definitive result in surveillance tabulations New HIV Testing Algorithms (slide 1)

5. Why are we Suggesting this Change?  The CLSI document describes algorithms that clinicians and labs are already using  We are making these changes so we can have the infrastructure in place to allow reporting of cases diagnosed using these new algorithms  We are not driving clinical practice- we are adapting surveillance to account for changes that are occurring

6. Why are we Suggesting this Change? (cont)  If we fail to develop a way to recognize cases diagnosed using the new algorithms we will undercount cases  as use of the new algorithms increases the number of cases we would lose increases  Implementation is complex but necessary

7. 7 Das G et al. BMJ 2010;341:bmj.c4583 Progression of HIV Viral Markers IgMIgG AcuteSeroconversion→Established

8.  What is new about the new algorithms?  Results of more sensitive and specific antibody tests formerly used only as initial tests for screening (e.g., immunoassays such as EIAs and rapid tests) may now be used as supplemental tests to confirm a case of HIV-infection after a positive result on another immunoassay New HIV Testing Algorithms (slide 2)

9. 9 Relative Sensitivity of Tests From: Branson, JAIDS, 2010, 55 (S2): S102-S105

10. New Testing Algorithms (slide 3)  Labs and healthcare providers may need guidance on how to report results from new multi-test algorithms to surveillance programs.  Labs may need to report results of both first and subsequent test(s) in algorithm, not just final test  Surveillance needs way to know both tests were part of same algorithm, not just unrelated screening tests  We expect implementation issues to be resolved by a workgroup that consists of representatives from areas with established lab reporting systems and CDC staff.

11.  New HIV testing algorithms  New: criteria for a suspect case  HIV-2 infection  Stage 0 HIV infection  AIDS-defining conditions (opportunistic illnesses)  CD4 test results for staging for adults/adolescents  HIV Case definition for children  Physician-documented diagnosis- PDD (clinical, rather than laboratory criteria for a confirmed case)  PDD - date of diagnosis Proposed Revisions

12. Suspect Case Criteria  Cases meeting the following criteria should be reported for follow-up and confirmation:  4 th gen IA positive (Ag/Ab test)  F/U antibody-only test is negative  NAT (normally used to confirm results above) is unavailable  Conclusion - case may be antigen positive/ antibody negative

13. Suspect Case - Rationale  Cases meeting criteria may represent acute HIV infection  Highly infectious - high viral loads  May not know their HIV status  High priority for follow-up by health department to obtain second specimen for NAT testing (if possible), notify of potential infectiousness, start partner notification process, refer into care for further testing and follow-up

14. Suspect Case - Concerns  Cases meeting criteria may be false positives  Sensitivity and specificity of 4 th generation IA is >99% (higher than the Western Blot we have been using to confirm cases as positive since the 1980s) so do not expect many false positives  If case is falsely positive sending health department out to obtain second specimen for NAT testing/refer patient to care for follow up testing will determine status  If HD unable to obtain NAT results, case can be changed to negative if received in the future

15. Suspect Case – Concerns (cont)  Are we expecting states to start routine collection of negative results? NO  We do not want nor expect all negative results to be reported BUT if the 4 th gen IA was + we would want negative results on antibody tests associated with that + reported if possible  We expect we will learn of these cases primarily from reports from clinicians who encounter them  Will know more as use of new lab tests increases

16. Suspect Case – Concerns (cont)  Inclusion of these cases in the case definition is to:  help states emphasize the importance of such cases and  give them the support to be able to report them  Inclusion of these cases is not required

17. Suspect Case - Steps Needed to Include in Position Statement  Not included in PS#12-ID-05 as submitted on March 29, 2012  Is included in June 1 version of the Position Statement (posted on CSTE website)  Addition is in section VII- Case Definition for Case Classification A.3 and A.3.a and Table VII-B.3

18. Suspect Case - Why Now?  Work groups and consultation on integrating new testing algorithms occurred before testing using new algorithms widely implemented  Once implementation began we realized that commercial labs would likely require a second blood draw with specimen received within 72 hours for confirmatory NAT testing  Lab reality: second draws occur infrequently and/or specimens not received within 72 hours  Consequently, need a process for cases described above and shown again in next slide

19. Suspect Case Criteria  Cases meeting the following criteria should be reported for follow-up and confirmation:  4 th gen IA positive (Ag/Ab test)  F/U antibody-only test is negative  NAT (normally used to confirm results above) is unavailable  Conclusion - case may be antigen positive/ antibody negative

20.  New HIV testing algorithms  New: criteria for a suspect case  HIV-2 infection  Stage 0 HIV infection  AIDS-defining conditions (opportunistic illnesses)  CD4 test results for staging for adults/adolescents  HIV Case definition for children  Physician-documented diagnosis- PDD (clinical, rather than laboratory criteria for a confirmed case)  PDD - date of diagnosis Proposed Revisions

21. HIV-2 Infection  HIV case surveillance should accept as sufficient for diagnosis of HIV-2 infection:  Positive initial test that can detect HIV-2 antibody (e.g., HIV-1/2 immunoassay) AND  One or more of the following: FDA-approved HIV 1/2 type-differentiating antibody test positive for HIV-2 and negative for HIV-1 or Positive HIV-2 nucleic acid test (NAT) or Positive HIV-2 Western blot/immunoblot (WB) and negative HIV-1 WB or Diagnosis by CDC-recognized expert in WB interpretation if positive HIV-2 WB and positive or indeterminate HIV-1 WB

22.  New HIV testing algorithms  New criteria for a suspect case  HIV-2 infection  Stage 0 HIV infection  AIDS-defining conditions (opportunistic illnesses)  CD4 test results for staging for adults/adolescents  HIV Case definition for children  Physician-documented diagnosis- PDD (clinical, rather than laboratory criteria for a confirmed case)  PDD- date of diagnosis Proposed Revisions

23. Stage 0 HIV Infection (slide 1) OR 30 days First confirmed positive HIV test (confirmed Ag/Ab positive or NAT) 180 days Negative or indeterminate HIV antibody test or negative/undetectable NAT/viral load Negative or indeterminate HIV antibody test followed by positive NAT

24. Stage 0 HIV Infection (slide 2) Exceptions  These criteria for Stage 0 do not apply to HIV-2  Stage 0 does not last >180 days after diagnosis date  Stage 0 is excluded if first positive test was preceded by >60 days by evidence of long-standing infection:  CD4 T-lymphocyte count <200 cells/µL  Physician documented diagnosis Otherwise, Stage 0 criteria are independent of CD4 T- lymphocyte test results and take precedence over criteria for other HIV stages

25. Expectations of Health Departments  This Position Statement does not imply that we expect you to start obtaining all negative reports-clearly a problem for most/all of us  Identifying an acute case will likely come from physicians or other testers and this definition is to allow us to capture these critically important cases

26.  New HIV testing algorithms  New: criteria for a suspect case  HIV-2 infection  Stage 0 HIV infection  AIDS-defining conditions (opportunistic illnesses)  CD4 test results for staging for adults/adolescents  HIV Case definition for children  Physician-documented diagnosis- PDD (clinical, rather than laboratory criteria for a confirmed case)  PDD - date of diagnosis Proposed Revisions

27. AIDS-Defining Conditions (Opportunistic Illnesses [OIs]) (slide 1)  OIs should be removed from criteria for Stage 3 (AIDS) in future staging among adults/adolescents, because  CD4 data adequately substitute for OI data as criteria for Stage 3  More direct measure of immune system damage  95% of cases meet Stage 3 criteria based on CD4 results  Most systems do not routinely collect OI data- expensive to collect

28. AIDS-Defining Conditions (Opportunistic Illnesses [OIs]) (slide 2)  OIs should be removed from criteria for Stage 3 (AIDS) in future staging among adults/adolescents, because  OI data collected by routine surveillance are too incomplete to be useful for analyzing OIs  Other projects and surveillance systems do a better job of collecting representative OI data than does routine HIV case surveillance (MMP)  Eliminating OIs from staging will simplify surveillance

29.  OIs should be kept as criteria for Stage 3 in children because CD4’s are not being used as criteria for Stage 3 in children, but  Whatever method was used to make an OI diagnosis should be accepted as sufficient for surveillance (eliminating requirement that some OIs be “definitively” diagnosed)  Lymphoid interstitial pneumonia should be removed from the list because it is associated with moderate rather than severe immunodeficiency AIDS-Defining Conditions (Opportunistic Illnesses [OIs]) (slide 3)

30.  New HIV testing algorithms  New: criteria for a suspect case  HIV-2 infection  Stage 0 HIV infection  AIDS-defining conditions (opportunistic illnesses)  CD4 test results for staging for adults/adolescents  HIV Case definition for children  Physician-documented diagnosis- PDD (clinical, rather than laboratory criteria for a confirmed case)  PDD - date of diagnosis Proposed Revisions

31. CD4 Test Results as Criteria for Staging in Adults/Adolescents  CD4 count should take precedence over CD4 percentage as criterion for staging; CD4 percentage should be criterion only if CD4 count is missing Reasons:  Clinicians consider CD4 count to have greater prognostic value than CD4 percentage  Some studies show CD4 percentage has little effect on prognosis after adjusting for CD4 count  CD4 percentage used as threshold between Stages 1 and 2 should be 26% instead of 29% (if data supporting this change are published)

32.  Use of term “AIDS” should be minimized in staging system (just call it “Stage 3”)  Permit alternative applications of staging system:  most severe stage experienced as of a particular date (for which changes in stage could be in only one direction--from less to more severe)  stage at initial diagnosis  stage based on most recent CD4 test results (for which changes could be in either direction, including from more to less severe); (excluding Stage 0 because not based on CD4 test results) Other Staging Issues

33.  New HIV testing algorithms  New: criteria for a suspect case  HIV-2 infection  Stage 0 HIV infection  AIDS-defining conditions (opportunistic illnesses)  CD4 test results for staging for adults/adolescents  HIV Case definition for children  Physician-documented diagnosis- PDD (clinical, rather than laboratory criteria for a confirmed case)  PDD - date of diagnosis Proposed Revisions

34. HIV Infection Case Definition for Children  For a diagnosis of HIV infection among children under 18 months of age,  Remove 2008 case definition’s requirement of HIV-infected mother for Definitive HIV infection and Presumptive HIV infection because laboratory test results can be sufficient to make those diagnoses,  but keep requirement of HIV-infected mother for indeterminate HIV infection, where required lab results are unavailable for definitive or presumptive diagnosis, and  for determination of absence of HIV infection among perinatally HIV-exposed children

35.  New HIV testing algorithms  New: criteria for a suspect case  HIV-2 infection  Stage 0 HIV infection  AIDS-defining conditions (opportunistic illnesses)  CD4 test results for staging for adults/adolescents  HIV Case definition for children  Physician-documented diagnosis- PDD (clinical, rather than laboratory criteria for a confirmed case)  PDD - date of diagnosis Proposed Revisions

36. Clinical Criteria for Confirmed HIV Case (Physician-Documented Diagnosis) (slide 1)  If physician’s written statement says patient had  positive result  on a particular type of HIV test  in a specific year (not stated to be only what patient said), then diagnosis should be considered laboratory-test-documented, not physician- documented (i.e., meets lab criteria, not clinical criteria)

37. Clinical Criteria for Confirmed HIV Case (slide 2)  If initial diagnosis is not laboratory-test- documented, but  physician’s note says patient has HIV infection (not stated to be only what patient said), and  subsequent diagnosis is laboratory-test-documented or  there is circumstantial evidence of HIV infection (with other explanations ruled out), such as Receipt of HIV-related care (e.g., antiretrovirals, OI prophylaxis, repeated CD4 tests and viral loads) CD4 count <350 cells/µL OI diagnosis then initial diagnosis is physician-documented

38.  Official date of diagnosis should be defined as: Date of diagnosis reported in physician’s note, even if inaccurate or inexact, not necessarily date on which note was written unless diagnosis date (year) was not reported in note  However, all dates should be collected, including  Diagnosis date reported by physician (not stated to be reported by patient)  Diagnosis date stated to have been reported by patient  Date note was written by physician Date of Physician Documented Diagnosis

39. Many thanks to CDC’s Richard Selik for all the work he did on this Position Statement: the initial writing and research, working with the workgroups which informed the decisions made at the February 2012 case definition consultation and on which this PS is based.

40. Eve Mokotoff Contact Info Eve Mokotoff, MPH MokotoffE@michigan.gov (V) 313.876.4769 (0353) (C) 313.407.7761 HIV/STD/VH/TB Epidemiology Section Michigan Department of Community Health 1151 Taylor Room 211B Detroit, MI 48202

41.  What is new about the new algorithms?  Results of more sensitive and specific antibody tests formerly used only for screening – EIA’s/IA’s – now used to define a case of HIV-infection  HIV-1/HIV-2 type-differentiating antibody (e.g., Multispot) test following IA screen may now be used to define a case of HIV-infection  If HIV-1/HIV-2 type-differentiating antibody test is negative a positive result on a qualitatively different test such as the NAT confirms the case as HIV- infected New HIV Testing Algorithms (slide 2)