HIV Surveillance Case Definition Position Statement #12-ID-05

Overview

CSTE MeetingJune 3, 2012

Omaha, Nebraska

Eve D. Mokotoff

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

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

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)

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

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

7Das G et al. BMJ 2010;341:bmj.c4583

Progression of HIV Viral Markers

IgM

IgG

Acute Seroconversion→Established

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

Relative Sensitivity of Tests

From: Branson, JAIDS, 2010, 55 (S2): S102-S105

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.

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

Suspect Case Criteria

Cases meeting the following criteria should be reported for follow-up and confirmation: 4th 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

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

Suspect Case - Concerns Cases meeting criteria may be false positives Sensitivity and specificity of 4th 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

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 4th 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

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

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

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

Suspect Case Criteria

Cases meeting the following criteria should be reported for follow-up and confirmation: 4th 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

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

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

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

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 testfollowed bypositive NAT

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

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

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

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

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

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)

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

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)

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

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

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

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

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)

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

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

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.

Eve Mokotoff Contact Info

Eve Mokotoff, MPHMokotoffE@michigan.gov(V) 313.876.4769 (0353)(C) 313.407.7761

HIV/STD/VH/TB Epidemiology SectionMichigan Department of Community Health1151 Taylor Room 211BDetroit, MI 48202