WHO/Euro Report of the Technical Consultation on Clinical Staging of HIV/AIDS and HIV/AIDS Case Definitions for Surveillance

Transcription

1 WHO/EURO REPORT OF THE TECHNICAL CONSULTATION ON CLINICAL STAGING OF HIV/AIDS AND HIV/AIDS CASE DEFINITIONS FOR SURVEILLANCE Copenhagen, Denmark May 2005

2 WHO/Euro Report of the Technical Consultation on Clinical Staging of HIV/AIDS and HIV/AIDS Case Definitions for Surveillance May 2005 Copenhagen, Denmark Prepared by: Sexually Transmitted Infections/HIV/AIDS Programme, WHO Regional Office for Europe

3 This report was prepared with the assistance of WHO HIV/AIDS Department in Geneva. The technical consultation was organized by WHO EURO in partnership with EuroHIV and the European Centre for Disease Prevention and Control (ECDC). Address requests about publications of the WHO Regional Office for Europe to: Publications WHO Regional Office for Europe Scherfigsvej 8 DK-2100 Copenhagen Ø, Denmark Alternatively, complete an online request form for documentation, health information, or for permission to quote or translate, on the WHO/Europe web site at World Health Organization 2005 All rights reserved. The Regional Office for Europe of the World Health Organization welcomes requests for permission to reproduce or translate its publications, in part or in full. The designations employed and the presentation of the material in this publication do not imply the expression of any opinion whatsoever on the part of the World Health Organization concerning the legal status of any country, territory, city or area or of its authorities, or concerning the delimitation of its frontiers or boundaries. Where the designation country or area appears in the headings of tables, it covers countries, territories, cities, or areas. Dotted lines on maps represent approximate border lines for which there may not yet be full agreement. The mention of specific companies or of certain manufacturers products does not imply that they are endorsed or recommended by the World Health Organization in preference to others of a similar nature that are not mentioned. Errors and omissions excepted, the names of proprietary products are distinguished by initial capital letters. The World Health Organization does not warrant that the information contained in this publication is complete and correct and shall not be liable for any damages incurred as a result of its use. The views expressed by authors or editors do not necessarily represent the decisions or the stated policy of the World Health Organization.

4 TABLE OF CONTENTS ACRONYMS...1 BACKGROUND...2 OBJECTIVES:...3 REPORT OF THE MEETING:...4 OPENING CEREMONY AND OVERVIEW OF PRESENTATIONS...4 PLENARY PRESENTATIONS...5 PROPOSED REVISIONS TO THE WHO CLINICAL STAGING OF HIV/AIDS IN ADOLESCENTS AND ADULTS AND CHILDREN DR. SIOBHAN CROWLEY...5 CURRENT HIV/AIDS SURVEILLANCE SYSTEMS IN EUROPE - DR. FRANÇOISE HAMERS...6 OVERVIEW OF PROPOSED REVISIONS TO HIV/AIDS CASE REPORTING FOR ADULTS AND CHILDREN AND ITS RELEVANCE TO WHO CLINICAL STAGING - DRS. GEORGE LOTH AND KATE GLYNN...7 GROUP WORK...8 CLINICAL STAGING OF HIV/AIDS (GROUPS #1 & #2)...8 TREATMENT OUTCOME INDICATORS (GROUP #3)...10 GROUP WORK REVIEW OF HIV/ AIDS CASE DEFINITIONS FOR SURVEILLANCE...11 MEETING CONSENSUS AND RECOMMENDATIONS...14 HIV/AIDS SURVEILLANCE...14 CLINICAL STAGING...15 PROGRAMME INDICATORS FOR ART...15 SUGGESTED NEXT STEPS TO WHO...15 TABLE #1: REVISED WHO CLINICAL STAGING OF HIV/AIDS FOR ADULTS AND ADOLESCENTS...17 TABLE # 2 REVISED WHO CLINICAL STAGING OF HIV/AIDS FOR INFANTS AND CHILDREN...18 KEY REFERENCES...20 ANNEX 1 OVERVIEW ECDC (K. IKDAHL) ANNEX 2 RATIONAL AND PROPOSED REVISED CLINICAL STAGING (S. CROWLEY) ANNEX 3 EUROPEAN HIV/AIDS CASE DEFINITION EUROHIV (F. HAMERS) ANNEX 4 CASE DEFINITION USED IN EURO EUROHIV ANNEX 5 CASE DEFINITION QUESTIONNAIRE EUROHIV ANNEX 6 INTRODUCTION TO SURVEILLANCE (G. LOTH) ANNEX 7 AIDS CASE DEFINITION (K. GLYNN) ANNEX 8 GROUP WORK CLINICAL STAGING ADULTS AND ADOLESCENTS DAY 1 GROUP 1 ANNEX 9 GROUP WORK CLINICAL STAGING CHILDREN DAY GROUP 1 ANNEX 10 GROUP WORK CASE DEFINITION ADULTS AND ADOLESCENTS DAY 2 GROUP 1 ANNEX 11 GROUP WORK CASE DEFINITION CHILDREN DAY 2 GROUP 2 ANNEX 12 SCOPE AND PURPOSE

5 ANNEX 13 ANNEX 14 PROGRAMME LIST OF PARTICIPANTS

6 ACRONYMS Ab Antibody AIDS Acquired Immuno-Deficiency Syndrome AIN Anal Intraepithelial Neoplasia ART AntiRetroviral Therapy ARV AntiRetroViral (drug) BCG Bacille Calmette-Guerin CD4 subgroup of T-lymphocytes (human T helper cells) carrying CD4 antigens CDC Centers for Disease Control and Prevention (USA) CHAPS Children with HIV AIDS Prognostic Study CIN Cervical Intra epithelial cellular Neoplasia CMV CytoMegalo Virus CNS Central Nervous System CS Clinical Staging EC European Commission ECDC European Centre for Disease Prevention and Control EURO WHO European Regional Office HAART Highly Active Anti-Retroviral Therapy Hb Haemoglobin HHV8 Human Herpes Virus type 8 HIV Human Immunodeficiency Virus HMIS Health Management Information System HPPMCS HIV Paediatric Prognostic Markers Collaborative Study HPV Human Papilloma Virus HSV Herpes Simplex Virus IMCI Integrated Management of Childhood Illness IRS Immune Reconstitution Syndrome LGE Linear Gingival Erythema LIP Lymphoid Interstitial Pneumonitis MOTT Mycobacteria other than TB MTCT Mother to Child Transmission OI Opportunistic Infection P24 a soluble antigen produced by HIV PCP Pneumocystis Carinii Pneumonia PCR Polymerisation Chain Reaction PGL Persistent Generalized Lymphadenopathy PKS Kaposi s Sarcoma PLWHA People Living With HIV/AIDS PML Progressive Multifocal Leukoencephalopathy PMTCT Prevention of Mother - To - Child Transmission PTB Pulmonary Tuberculosis RTI Respiratory Tract Infection Rx Treatment 4Ss Starting, Substitution, Switching, Stopping TB Tuberculosis VL Viral Load WHO World Health Organization 1

7 INTERIM WHO CLINICAL STAGING OF HIV/AIDS AND HIV/AIDS CASE DEFINITIONS FOR SURVEILLANCE BACKGROUND AIDS case definitions for surveillance were first developed to track and monitor disease, later established to be attributed HIV virus infection. Surveillance definitions were first introduced in 1982, and have been revised over the years for use in national and international reporting (1). Considerable advances in the understanding of the pathogenesis and the pattern of disease, and new advances in diagnosis and treatment have occurred since the original WHO HIV/AIDS surveillance definitions were first developed and subsequently revised in In Europe, the majority of countries are presently using the European Case Definition for AIDS Surveillance, which was revised in It is based on the 1987 CDC case definition and includes three additional diseases for adults and adolescents: 1) pulmonary TB; 2) invasive cervical cancer, and, 3) recurrent pneumonia. It differs from the 1993 CDC revision (currently used in the US) in that it does not include the biological criterion of a CD4 cell count less that 200 per mm 3. The advent of HAART * and the scale up of access to ART in low and middle income countries has necessitated re-examinations of the surveillance related definitions and the classification of staging systems used to describe the spectrum of HIV related illness. HIV related disease, including that which currently needs or will soon need ART can be reversed with ART and the onset of AIDS can be deferred; hence, AIDS surveillance systems do not capture the true burden of disease requiring ART. In addition, confusion has occurred with clinical case definitions for surveillance being used for clinical purposes. The clinical staging of HIV/AIDS was originally developed to provide a guide to the prognosis of HIV infection and to guide treatment and care related decisions. There are currently two main HIV disease classification systems developed by CDC and WHO respectively. The WHO clinical staging system of HIV/AIDS developed in 1990, emphasized use of clinical parameters to guide clinical decision making for management of HIV/AIDS patients. It was designed for use in resource-limited settings with limited access to laboratory services. The other key clinical staging system of the US CDC provides staging based on immunological parameters (CD4 counts) and clinical parameters as well as requiring laboratory confirmation of many of the clinical events, but was designed for the surveillances purposes. Improved understanding of the pathogenesis of HIV infection, and improved laboratory technologies including CD4 and viral load monitoring have provided clinicians with greater insight into how to best manage HIV infection including paediatric HIV infection. This and the shift towards HIV being seen and managed as a chronic disease, require examination of both the disease staging (or classification) and optimum reporting points and surveillance definitions. Revisions of the existing HIV clinical staging system should also improve clinical decision-making and improve patient management and could be * HAART is the term used when a minimum of 3 ARV drugs are administered together ART is the broad term used for antiretroviral treatment 2

8 important in facilitating global efforts to expand access to treatment in resource limited settings. In response to the above needs, WHO organized a meeting in Saas Fee, Switzerland in June The meeting proposed a revised WHO clinical staging system for HIV infection in adults and children, recommended review and discussion of HIV/AIDS case definitions for surveillance purposes, and sought to harmonize the HIV clinical staging with the HIV/AIDS surveillance definitions. It recommended regional consultations on the proposed revisions. The regional meetings would also offer the chance to explore how clinical staging could be used to improve patient management and case reporting, This European regional meeting was conducted to ensure that HIV clinical, programme and surveillance experts from the countries of the region were given the opportunity to review and recommend changes or additions to the revision of the clinical staging system and review HIV/AIDS surveillance activities and definitions within the region. Objectives: The general objective of the workshop was to reach consensus on a clinical staging system and review HIV/AIDS case definition for surveillance in the European region. The specific objectives were: 1. To familiarize regional expert participants with the proposed revisions to the HIV/AIDS clinical staging system and HIV/AIDS case definitions for surveillance 2. To review the revisions proposed and HIV/AIDS case definitions for surveillance. 3. To identify and agree on any additions or regional adaptations to the HIV/AIDS clinical staging system and HIV/AIDS case definitions for surveillance that may reflect the needs and realities of the European region. 4. To make recommendations on how to improve the use of the HIV clinical staging system and on HIV/AIDS case definitions for surveillance. The expected outcomes of the meeting were to: Reach consensus on regional recommendations for WHO clinical staging system for HIV/AIDS in adults, adolescents and children. Reach consensus on any revisions to HIV/ AIDS case definitions for surveillance. 3

9 REPORT OF THE MEETING: OPENING CEREMONY AND OVERVIEW OF PRESENTATIONS The EURO regional consultation meeting on proposed revisions to HIV clinical staging and HIV/AIDS case definitions for surveillance was held at the WHO European Regional Office (EURO) in Copenhagen, Denmark, 24 th 26 th May It was organized by EURO in partnership with EuroHIV and the European Centre for Disease Prevention and Control (ECDC), and was attended by participants from 17 countries of the region as well as representatives from partner organizations, including, the Centers for Disease Control and Prevention (CDC) US, UNAIDS and WHO experts from Geneva. Dr. Gudjón Magńusson, Director of the Division of Technical Support of Reducing Disease Burden, opened the meeting and gave welcome remarks, highlighting the need for technical programmes to be instrumental in securing access to ART in a qualified evidence based manner. He underscored the need and use of evidence based information, given that health intelligence is only at its best when concrete evidence is available, and that evidence based methods contributes to identifying substantiated facts and gaps in knowledge to combat the epidemic. Dr Kate Glynn of CDC indicated in her opening remarks that CDC would also be reviewing and revising its AIDS case definition and HIV classification system this year. They would be considering both domestic and global perspectives in this undertaking. During the presentation of the objectives and outcomes of the meeting, Dr. Srdan Matic, Regional Advisor EURO, pointed out that: clear concise standard case definitions are needed in the era of ART; there is a need for standardized monitoring and evaluation of treatment outcomes in the region; and, there is a necessity of a basic set of indicators to monitor treatment outcomes for the European Region. Such indicators should look at efficacy and efficiency of ART and assist in setting up fundamental guidelines for years to come. Dr. George Loth, WHO Geneva, drew attention to the fact that the clinical staging and HIV/AIDS case definitions have not been reviewed or revised in the last 12 years, in particular paediatric clinical staging, and that clinical staging definitions and case definitions, are being used interchangeably by clinicians and epidemiologists. The ongoing efforts to expand treatment access, including the 3 by 5 Initiative, have provided the impetus to re-look at these issues. The Strategic Advisor to the Director, Dr. Karl Ekdahl, of the newly launched ECDC introduced the current situation and the future role of ECDC in general and that of the work they shall be undertaking in the area of HIV/AIDS (see Annex 1 for presentation). ECDC s role is to strengthen and coordinate other institutions and systems that already exist. ECDC will be working closely with EuroHIV, which will probably be integrated 4

10 into ECDC at some later stage. ECDC will be working collaboratively with WHO, and will increasingly take part in policy development. PLENARY PRESENTATIONS Proposed revisions to the WHO clinical staging of HIV/AIDS in adolescents and adults and children Dr. Siobhan Crowley (annex 2) Development and adoption of AIDS case definition for surveillance purposes began in the mid 1980 s; the clinical staging for adults was first proposed by WHO in There is still poor understanding of the differences between AIDS case definitions for surveillance and case definitions used within clinical practice. AIDS case surveillance in the era of ART does not provide a complete picture of the burden of HIV related disease, and does not allow for the determination of the burden of HIV related disease that requires ART and other clinical interventions. Not all conditions that are AIDS defining for surveillance purposes are considered equivalent (e.g. Tuberculosis and recurrent pneumonia). The key purposes of a clinical staging are to: assist with clinical decisions with regards to ART (starting, substitution, switching and stopping Four S s) and other prophylaxis be used to guide clinical decision making where CD4 and Viral Load (VL) are not easily available for either adults or children) harmonize definitions so that there is consistency between the adult and paediatric staging systems and case definitions assist in all stages of clinical care (pre ART and on ART) The key features of the proposed revisions to the clinical staging are: a more comprehensive list of associated clinical conditions based upon prognosis (much expanded list of conditions in children) standardized criteria for presumptive clinical and definitive diagnosis harmonized adult and paediatric staging (4 stages) harmonized with HIV surveillance definitions provide links to clinical decision triggers for starting, substitution, switching, stopping ART relate clinical stages to patient monitoring on and off ART The key issues requiring review at this consensus meeting were: given that there are often multiple signs and symptoms of HIV infection, is a constellation or a single clinical event more important for disease classification? the utility of standardised presumptive and definitive diagnosis additional conditions or ones to be excluded based on the spectrum of HIV disease in countries of the region the utility of immunological staging/criteria relevance of a staging system once on ART relevance of clinical 'AIDS' case definition for clinical care with ART operational research required to validate revisions to staging classifications, and fieldtest the 'presumptive and definitive clinical criteria' how to position TB within the staging systems 5

11 possibilities to build in other simplified indicators e.g. Hb Current HIV/AIDS surveillance systems in Europe - Dr. Françoise Hamers (annex 3, 4, 5) European AIDS case reporting has been on going since HIV case reporting has been occurring at national levels since the late 1980 s in most countries (exceptions include Italy and Spain which have to date, not yet implemented HIV case reporting at national level) and at the European level since In 1993, CDC expanded its AIDS case definition to include HIV infected adults/adolescents with <200 CD4 whether symptomatic or not, and 3 additional indicator diseases: pulmonary tuberculosis, recurrent pneumonia, and invasive cervical cancer. The European definition includes the three new indicator diseases but does not include CD4 count <200/µL without opportunistic illness. The European case definition in children is presently consistent with the CDC 1994 revised classification system. In a survey conducted by EuroHIV in May 2005, among the 52 countries of the WHO European Region, it was found that of the 46 countries that responded 34 (74%) use the 1993 European definition, 8 (17%) use the CDC definition and 4 (1%) use either the 1994 or 2002 WHO definition. Among the 25 countries of the enlarged European Union, all but one use the European AIDS case definition. Almost half (20) the countries reported that AIDS case surveillance was still useful in the era of ART, while a further 20 reported it as somewhat useful. Three countries reported AIDS case surveillance as no longer useful. Some of the reasons given in the survey as to the continued usefulness of having AIDS case reporting are: provides information on treatment failure allows comparison over time and across countries link with other surveillance systems AIDS defining illnesses combined with HIV diagnosis provides a marker of late diagnosis useful for planning cost of treatment useful for evaluation of ART Issues that remain outstanding with regards to both AIDS case reporting and HIV case reporting, include: AIDS case reporting Since the advent of HAART, AIDS incidence trends are no longer informative of the underlying HIV incidence trends. AIDS case reporting can no longer be used as a marker for the natural history of the disease. AIDS incidence has essentially become a measure of late diagnosis of HIV, late presentation or failure of ART. Completeness of reporting: - has probably always been low in eastern Europe - is probably decreasing in western Europe 6

12 The surveillance focus has been shifted to HIV case reporting. HIV case reporting does not measure HIV incidence depends on the uptake of HIV testing as for other chronic disease surveillance and AIDS, requires efficient systems to eliminate duplicate reporting generates greater concern for confidentiality than for AIDS case reporting Overview of proposed revisions to HIV/AIDS case reporting for adults and children and its relevance to WHO clinical staging - Drs. George Loth and Kate Glynn (see presentations in annex 6 & 7) The purpose of HIV/AIDS surveillance is basically to: monitor the epidemic Who, What, Where, When, How monitor and guide public health responses to the epidemic measure burden of severe disease in relation to ART There are various types of surveillance methods and strategies that exist, each with their own objective, strengthens and weaknesses. AIDS case reporting was originally designed to be used to identify people severely ill as a result of HIV infection, prior to the availability of HIV specific testing, and was designed to be simple, specific and consistent. As tracking the number of new cases of HIV infection (incidence) is difficult, AIDS case surveillance has been used for many years to track the extent of the epidemic, and estimate the burden of advanced and severe HIV. In resource constrained countries AIDS underreporting has been estimated at approximately 15%, although this ranges from 0% to 25%. WHO estimates that in sub-saharan Africa 80-90% underreporting occurs. With the advent of HAART and increasing use of antiretroviral (ARV) drugs the number of AIDS cases reported has decreased, and been associated with markedly lowered HIV/AIDS mortality. Current AID case definitions do not reflect the numbers of people who need ART, as ART is ideally started prior to and prevents the development of AIDS. Programmes need more useful information to assist in the planning and management of ART and HIV care services. 7

13 GROUP WORK Clinical Staging of HIV/AIDS (Groups #1 & #2) Two working groups reviewed the proposed revisions to the clinical staging of HIV/AIDS; one group reviewed the adult staging and the other reviewed that for children. Both groups discussed the purposes of clinical and immunological staging, reviewed the revised WHO clinical staging, immunological criteria and listed conditions, in addition, the considered how clinical staging may be used where there is apparent reversing of clinical stage and immunological stage on ART. Both groups agreed that clinical staging (CS) is useful to: determine prognosis on presentation and initial assessment of disease guide decision making for initiating treatment (ART) and prophylaxis of opportunistic infections Participants were clear that the staging system is not a diagnostic algorithm and is only for use once HIV infection has been established. Other purposes highlighted during discussions were: potential use for monitoring clinical outcomes on ART recognition and understanding of spectrum of disease; useful for educating health care professionals, to think about HIV in differential diagnosis and as an indication for HIV testing public health benefits recognition of late presenters and looking at missed opportunities for earlier diagnosis, etc The two groups were not completely sure that the existing clinical staging remains useful and hierarchical during ART and for monitoring of ART treatment, although both groups recommended this should be urgently evaluated. The staging needs to consider current and the worst ever clinical stage and when possible, CD4 counts or immunological classification. For now it must be assumed conditions retain the same hierarchy on ART. It was also suggested that treatment recommendations should be maintained separately from the clinical staging, as they may well change over time. Treatment guidelines need to be updated frequently, and should refer to clinical and immunological stages. Both working groups agreed that the term AIDS is no longer as important for clinical purposes, and that AIDS represents clinical stage 4 HIV disease. It was however agreed that the term AIDS remains useful for other reasons (e.g. advocacy, etc.) and should therefore be retained as understood. Immunological staging is useful but the immunological and virological indicators should be separate from clinical staging and should be used to complement clinical parameters. It was recommended that CD4% should be included (not just for children) and CD4 <50 might be considered as this usually heralds a worse prognosis and a more stormy clinical (For further details please see the corresponding presentation in the annex indicated.) 8

14 course on ART with a greater likelihood of immune reconstitution syndrome (IRS). For children, further examination of the immunological thresholds is recommended. HIV/AIDS Clinical staging in adults and adolescents: For adult and adolescent clinical staging it was suggested that further data on the immunological status of those presenting with pulmonary and extra pulmonary TB should be examined to guide where these conditions should be best placed within the staging systems. It was also suggested that significant and common co-morbidities particularly Hepatitis B and C should be mentioned as footnotes within the staging system; however, no consensus was reached to include this. For further details on the group work for clinical staging of adults and adolescents, please see annex 8. Table #1 (please see page 17) reflects the revisions to clinical staging of HIV/AIDS for adults and adolescents proposed by participants during the meeting. HIV/AIDS Clinical staging in children: Participants reviewed the proposed clinical staging of HIV/AIDS in children (annex 9) and agreed that clinical staging should be harmonised with adults and therefore should be four stages. Primary HIV infection is not a useful category when classifying children who mostly acquire infection during pregnancy, childbirth or the early neonatal period. Infants rarely present with an acute sero-conversion illnesses. It was suggested to retain conditions unusual in European populations of HIVinfected children (such as Kaposi sarcoma) as increasingly children who acquired HIV in different geographic regions will be first diagnosed in European region countries. Table 2 summarizes the recommended changes. It is only relevant to split other presenting conditions if there are robust data to indicate that some of these conditions are better prognostically than others. For tuberculosis, extra pulmonary and pulmonary TB are classified for surveillance purposes differently for children; it was agreed this best reflects the pattern of HIV associated TB in children. Accurate assessment of the degree of immune damage can really only be made with, CD4 % (or absolute count), and is recommended for optimal management of HIV infected children. Neutropenia should be defined as <500: the current cut-off of 1,000 may be within the normal range for many ethnic groups. Table #2 (please see page 18), reflects the revisions to clinical staging of HIV/AIDS for children proposed by participants during the meeting. 9

15 Treatment Outcome Indicators (Group #3) A third group examined the need for a common set of indicators that would be useful for countries to monitor national ART treatment programmes. This would be useful to allow comparisons across and within national programmes, and to provide information on the quality, access and effectiveness of ART services. Participants tried to define the minimal essential components that need to be captured. Variations in national collection of data depend on size, health care systems and resources available. Possible sources or methods to gather needed information includes: Cohort facility based studies for detailed information Cross sectional surveys of health care facilities Tabulations from regional cohorts and case reports A number of questions need to be addressed when developing treatment outcome indicators, they are: What is the purpose of collecting the information? Programme evaluation - Quality - Effectiveness - Access - Planning Usefulness for improving clinical care Is it necessary to collect treatment outcome indicators on all points? Should case reporting versus aggregate data be used if confidentiality is to be considered? Should existing systems be changed considering the costs involved? When addressing treatment outcomes different populations of HIV infected populations need to be identified and considered when developing criteria for indicators; they are: the undiagnosed HIV infected the diagnosed HIV infected those in need of ART those receiving ART those with treatment failure, delays in presenting, adherence issues, resistance to treatment deaths of those on ART deaths of those not on ART Diagram #1 illustrates populations to be considered. 10

16 Diagram #1: HIV INFECTED POPULATION Undiagnosed Diagnosed Need ART Receiving ART Failures? Adherence? Resistance?? Measure (estimate)? Measure? Criteria? Measure? Measure? National/Other The group felt that this was linked to active surveillance and case reporting Group Work Review of HIV/ AIDS Case Definitions for Surveillance Group #1: Review of HIV/AIDS Surveillance Definitions in Adolescents and Adults (annex 10) and Group #2: Review of HIV/AIDS Surveillance Definitions in Children (annex 11) The two groups examined and considered the required reporting for HIV and AIDS, and the proposed revised surveillance definitions adopted by the Africa region. Both groups identified the importance and need of information at different periods of time in infection. Information that should be gathered from surveillance in the era of ART at the European level should be of all HIV infections, diagnosed and estimated number of undiagnosed cases. HIV case reporting is considered the cornerstone of HIV/AIDS surveillance in Europe. Both groups felt that it is only reasonable to have three active points of reporting: (see diagram #2 below) 1. Point of diagnosis: reported variables should include: demographics, transmission group, and clinical stage. CD4 count or percentage should be added and if available, viral load. 2. Point at which AIDS is diagnosed: Reported variables should include use of antiretroviral treatment prior to AIDS diagnosis and CD4. 11

17 3. death in an HIV infected individual However, it was discussed and recognized that this does not provide a reporting point which indicates when ART is required. Diagram #2 Both groups considered whether a revised surveillance event, of all stage 3 and 4 disease with or without a CD4 criteria <350 would be useful. This, for the most part, represents those currently or soon requiring ART. This is clearly not equivalent to AIDS. As not all countries in the region have HIV reporting, it was felt that it would be more useful to ensure HIV reporting is undertaken, rather than revise or expand AIDS case reporting or introduce a new reporting event. The group reviewing paediatric case definitions felt that a clinical definition of AIDS or a surveillance definition of AIDS was not really very relevant or useful in the era of combination ART, and that HIV reporting and improved death reporting among HIV infected children would be far more useful. The group reviewing adult case definitions felt HIV case reporting should be implemented in all European countries and should: have standardised laboratory definition (this should be reviewed and examined in collaboration with lab experts) have individual data include AIDS defining event at HIV diagnosis, if present include CD4 count have all this in addition to already collected data (demographics, risk, etc.) 12

18 They also felt that the existing AIDS case surveillance should be maintained, using existing AIDS case definitions, as this would allow monitoring time trends and comparing countries given current incompleteness/immaturity of HIV case reporting. It was felt sensible not to change the existing AIDS case definition (for example adding CD4 criteria) as this would disrupt the trends already documented. It was however, agreed that the common AIDS surveillance definitions across Europe would help in advocacy, and to monitor late treatment access/uptake and failure of ART. In addition, it was suggested that additional information on ART would be useful including CD4 at HIV and ART at AIDS diagnosis. While participants could understand the rationale for reporting on advanced HIV disease (e.g. stage 3 /4 or first ever CD4 < 350 ) the groups felt that it would be more useful to enhance HIV case reporting than introducing this new reporting point for countries in the EURO region. Both groups were keen to attempt to harmonize clinical and surveillance definitions where possible, agreed to minor revisions such as all children considered for surveillance and staging as < 15 years, and suggested review of the HIV surveillance definitions to reflect advances in laboratory practice. 13

19 MEETING CONSENSUS AND RECOMMENDATIONS: HIV/AIDS SURVEILLANCE 1. It was proposed to use 15 years as the cut off for HIV case definitions for surveillance. (WHO EURO & EuroHIV) 2. Surveillance in the EURO region should focus on improved complete HIV case reporting and improving death registration in those who are known to be HIV infected. (WHO EURO & EuroHIV) 3. The existing AIDS case definition for surveillance should be retained. This would allow the possibility of monitoring time trends and enhance the ability to compare countries within the European region. For most countries in the EURO region it makes more sense to encourage countries to move to more complete HIV case reporting based on standardized case definitions. (WHO EURO) 4. All 52 European States should be encouraged to use the existing European HIV and AIDS case definitions. The European Commission, in collaboration with EuroHIV should be encouraged to undertake the formal process to review and update European HIV and AIDS case definitions. (WHO EURO & European Commission) 5. Existing HIV case definitions also need some revisions to better reflect developments in diagnostic technology and standardize the laboratory definitions, including the removal of inconsistencies; this would require consultation and collaboration with laboratory experts. (WHO EURO) 6. It was recommended that WHO EURO needs to review and examine the surveillance and reporting for PMTCT and pregnancy in HIV infected women, as this was beyond the scope of this meeting. (WHO EURO) 7. Ensure that countries, policy makers and health planners understand that AIDS case reporting cannot be used for resource allocation and planning or to predict health system resource requirements, as the intensity of health system demand occurs prior to the development of AIDS as currently reported. (WHO EURO) 8. Countries will need other cross sectional studies or data collections to be able to track or address other aspects of ART and treatment outcomes ; there are existing cohorts or collaborative efforts in the EURO region that are in position to examine some of the elements (strongly recommended they be used to answer some of the questions). (WHO EURO) 9. Reporting of the clinical and immunological stage of the person should be included at the time of the first HIV diagnosis. In addition, AIDS case reporting should include CD4 and ART history. (WHO EURO) 14

20 CLINICAL STAGING 10. It was proposed that clinical staging of HIV/AIDS use the same cut-off age of 15 years as is to be used for HIV case definitions for surveillance. 11. A WHO clinical staging system should be made available to EURO countries; this should be accompanied by an immunological classification based on known risks of HIV disease progression. (WHO EURO) 12. The proposed WHO staging reviewed in the meeting was accepted by participants although it was suggested that the criteria for children could be improved. 13. Revised staging tables (see Tables 2 & 3) were proposed with specific revisions to both presumptive and definitive diagnostic criteria. 14. Notable conditions where discrepancies between staging and AIDS case definitions currently found are for TB and LIP. 15. Further analysis of existing data sets and cohorts already available in the region should be examined to inform the prognostic placing of some conditions, and may allow inclusion of some additional conditions such as AIN, CIN and other neoplastic conditions. In particular, additional research or examination of regional specific date should be undertaken to examine: (WHO EURO) Relationship between CD4 and OI TB, and CD4 and prognosis Anogenital cancer Papular pruritic eruptions-if this is usually an indication of eligibility for ART Lymphomas- T cell -lymphoma, Hodgkin s and non-hodgkin s 16. Paediatric and adult clinical staging should be harmonized if possible, and should correspond to definitions used for surveillance. (WHO EURO) PROGRAMME INDICATORS FOR ART 17. Death due to HIV/AIDS needs to be better defined and methods to capture other ART related outcomes should be examined. ICD classifications may need revisions to reflect ART (WHO EURO) 18. For monitoring treatment related outcomes information on the following needs to be collected: (WHO EURO) Reported deaths: HIV related, AIDS related, non-related AIDS deaths of PLWHA Active AIDS death reporting versus passive reporting Basic ART information on AIDS and AIDS related death 19. Standardized reporting formats and procedures should be encouraged for use in EURO region countries. (WHO EURO) SUGGESTED NEXT STEPS TO WHO 15

21 1. Develop common electronic reporting system for critical surveillance elements identified above for countries (it should be noted that this is currently underway with ECDC). 2. Conduct a technical consultation on PMTCT surveillance and reporting, and to examine case definitions for uninfected and indeterminate infection in children. 3. Initiate the process of review of AIDS case definition and definitions of HIV infection e.g. review of Commission decision 2002/253/EC 4. Develop a harmonized clinical and immunological staging guidance for EURO countries, with separate treatment recommendations or surveillance recommendations. 5. On-going review of clinical staging and HIV/AIDS case definition should be undertaken on a regular basis. The interim clinical staging and revised definitions for surveillance are currently being reviewed in the other WHO regions and will be finalized at a global meeting to be held in September

22 Table #1: Revised WHO Clinical Staging of HIV/AIDS for Adults and Adolescents REVISED WHO CLINICAL STAGING OF HIV/AIDS FOR ADULTS AND ADOLESCENTS (Interim European region version for persons aged 15 years with positive HIV antibody test or other laboratory evidence of HIV infection) Acute HIV infection Asymptomatic Acute retroviral syndrome Clinical stage 1 Asymptomatic Persistent generalized lymphadenopathy (PGL) Clinical stage 2 Seborrhoeic dermatitis Angular cheilitis Recurrent oral ulcerations (2 or more episodes in 6 months) Herpes zoster (extensive zoster across 1 dermatome) Recurrent respiratory tract infections (2 or more episodes in any 6 month period of sinusitis, otitis media, bronchitis, pharyngitis, trachetis) Fungal nail infections Papular pruritic eruptions Clinical stage 3 Oral hairy leukoplakia Unexplained chronic diarrhoea for longer than one month Recurrent oral candidiasis (2 or more episodes in 6 months) Severe presumed bacterial infections (e.g. pneumonia, empyema, pyomyositis, bone or joint infection, meningitis, bacteraemia) Acute necrotizing ulcerative stomatitis, gingivitis or periodontitis Clinical stage 4 Pulmonary tuberculosis Extrapulmonary tuberculosis (excluding lymphadenopathy) Unexplained weight loss (more than 10% within 6 months) HIV wasting syndrome Pneumocystis pneumonia Recurrent severe or radiological bacterial pneumonia (2 or more episodes with 1 year) CMV retinitis (+/-colitis) HSV (chronic or persistent, 1 month) Encephalopathy HIV associated Cardiomyopathy HIV associated Nephropathy PML Kaposi's sarcoma & HIV related malignancies Toxoplasmosis Disseminated Fungal infection (e.g. candida,, Coccidomycosis, Histoplasmosis) Cryptosporidiosis Cryptoccocal Meningitis Non tuberculous mycobacterial infection or Disseminated MOTT * Possibly to be included in Stage 4 if evidence based data supports suggestions: Anal cancer and Lymphoma (T cell Hodgkin lymphoma 17

23 Table # 2 Revised WHO Clinical Staging of HIV/AIDS for Infants and Children REVISED WHO CLINICAL STAGING OF HIV/AIDS FOR INFANTS AND CHILDREN (Interim European region version for persons aged <15 years with confirmed laboratory evidence of HIV infection: HIV antibody if aged 18 months; virological or p24 antigen testing if aged <18 months) Clinical Stage 1 Asymptomatic Persistent generalized lymphadenopathy (PGL) Clinical Stage 2 Hepatosplenomegaly Papular pruritic eruptions Extensive molluscum contagiosum Fungal nail infections Recurrent oral ulcerations Lineal gingival erythema (LGE) Angular cheilitis Parotid enlargement Herpes zoster Asymptomic Lymphoid interstitial pneumonitis (LIP) Recurrent or chronic respiratory tract infections (RTIs) (otitis media, otorrhoea, sinusitis) Clinical Stage 3 Moderate unexplained malnutrition not adequately responding to standard therapy Unexplained persistent diarrhoea (14 days or more) Unexplained persistent fever (intermittent or constant, for longer than one month) Oral candidiasis (excluding first 2months of life ) Oral hairy leukoplakia Acute necrotizing ulcerative gingivitis or periodontitis Lineal gingival hyperplasia Severe recurrent presumed bacterial pneumonia Extensive and confluent warts Giant, disfiguring molluscum, Chronic HIV-associated lung disease including brochiectasis Symptomatic Lymphoid interstitial pneumonitis (LIP) Unexplained anaemia (<8g/dl), and or neutropenia (<500/mm3) Unexplained thrombocytopenia (<50 000/ mm3) for more than one month Clinical Stage 4 Unexplained severe wasting or severe malnutrition not adequately responding to standard therapy Recurrent severe presumed bacterial infections (e.g. empyema, pyomyositis, bone or joint infection, meningitis, but excluding pneumonia) Chronic herpes simplex infection; (orolabial or cutaneous of more than one month s duration) Extrapulmonary TB Kaposi s sarcoma Oesophageal candidiasis CNS toxoplasmosis (outside the neonatal period) HIV encephalopathy Cytomegalovirus (CMV) infection (CMV retinitis or infection of organs other than liver, spleen or lymph nodes; onset at age one month or more) Extrapulmonary cryptococcosis including meningitis Any disseminated endemic mycosis (e.g. extrapulmonary histoplasmosis, coccidiomycosis, penicilliosis) Cryptosporidiosis Isosporiasis 18

24 Disseminated non-tuberculous mycobacteria infection Candida of trachea, bronchi or lungs Visceral herpes simplex infection Acquired HIV associated rectal fistula Cerebral or B cell non-hodgkin lymphoma Progressive multifocal leukoencephalopathy (PML) HIV-associated cardiomyopathy or HIV-associated nephropathy (further information and evidence relating to occurrence and definitions of these conditions and their definitions are being sought) Leiomyosarcoma and other HIV related solid tumours 19

25 KEY REFERENCES 1. Interim WHO clinical staging of HIV/AIDS and HIV/AIDS case definitions for surveillance; African Region; December Revision and update of HIV Clinical Staging and AIDS Case Definition in the Era of Expanding Access to Antiretroviral Treatment in Resource-Limited Settings; Saas Fee, Switzerland, June Appendix: Revised Surveillance Case Definition for HIV Infection; CDC; MMWR December 10, 1999/48(RR 13); (just the appendix) 4. Summary of AIDS Case Definitions in use world wide 1997, WHO 5. European AID Case Definition for AIDS Surveillance in Children, Revision 1995; European Centre for the Epidemiological Monitoring of AIDS, Fourth Quarterly 1995, WHO case definitions for AIDS surveillance in adults and adolescents; WHO Weekly Epidemiological Report 1994, 69, Revision of the European AIDS Surveillance Case Definition; European Centre for the Epidemiological Monitoring of AIDS, Fourth Quarterly #37 31st March CD-ROM: UNAIDS/ WHO (Dec 2004) Second Generation Surveillance for HIV; Compilation of Basic Material Geneva: UNAIDS/WHO/EC 9. Guidelines for HIV Surveillance Among Tuberculosis Patients; Second Edition 2004; WHO 10. Commission Decision of 19 March 2002, Laying down case definitions for reporting communicable diseases to the Community network under Decision No 2119/98/EC of the European Parliament and of the Council; Official Journal of the European Communities, EC 11. AIDS case definition for surveillance purposes: national practices. EuroHIV. HIV/AIDS Surveillance in Europe. End-year report Saint-Maurice: Institut de veille sanitaire, 2005; No