1. Indicator Diseases guided-testing for HIV Antonella d´Arminio Monforte Jose M Gatell

2. Indicator Disease-guided testing for HIV 1.Why more testing ? 2.No rules vs. opt-out policy 3.Indicator disease-guided testing 4.How to identify indicator diseases 5.The HIV in Europe initiative on inidicator disease-guided testing for HIV 6.How to implement the recommendations

3. CD4 count at start of ART, 2003-2005 42 countries, 176 sites, 33,008 patients 187 181 159 87 97 122 86 100 125 123 97 239 103 53 72 192 163 206 157 134 102 200 179 95 CROI 2007 – CD4 at start – 10 164 Numbers are median CD4 counts

4. 4 U.S. HIV Market Dynamics 1,056 – 1,156 835 – 915 560 Significant Opportunity Remains in Increasing Diagnosis and Bringing Patients onto Therapy ~79%~83% 675 ~75% Sources: * February, 2009 CDC estimates as of the end of 2006 ** Synovate Healthcare U.S. HIV Monitor Q3 2008

5. 5 577 403 302 ~70%~82% 369 ~92% Sources: * National Surveillance Units per country & ECDC ** IMS/GERS & Synovate Q3 2008 EU Big 5 HIV Market Dynamics Similar Dynamics as Seen in the U.S. with Strong Support in the EU for Increased Testing Initiatives and Early Treatment

6. Late presenters in Europe  Most patients infected with HIV across the Europe remain undiagnosed; this percentage varies markedly from 15-80% across the continent.  Undiagnosed HIV is harmful to the person infected as appropriate health interventions are then delayed until the HIV infection is diagnosed.  It is also detrimental to society as persons unaware of their HIV infection may transmit more frequently to others than persons that are aware of their HIV status.  Finally, late presentation is associated to increased medical costs

7. Estimation of the new annual infections for sexual transmission between carriers of HIV 75% Identified 25% Unidentified 46% of new infections 54% of new infections Estimation more conservative hypothesis USA ( Marks G, Crepaz N, Janssen RS. AIDS 2006. ) New infections for sexual transmisionHIV +

8. Indicator Disease-guided testing for HIV 1.Why more testing ? 2.No rules vs. opt-out policy 3.Indicator disease-guided testing 4.How to identify indicator diseases 5.The HIV in Europe initiative on inidicator disease-guided testing for HIV 6.How to implement the recommendations

9. 9 CDC Recommendations for HIV Testing in Healthcare Settings  Routine voluntary testing for patients ages 13 to 64 years in healthcare settings –Not based on patient risk  Opt-out testing –No separate consent for HIV –Resulting in increases in HIV testing rates  Pretest counseling not required  Repeat HIV testing left to discretion of provider, based on risk  Within the US, 34 states are neutral to supportive of the CDC guidelines while 11 states have taken steps to reduce regulatory barriers –6 states passed legislation (2007) Branson BM, et al. MMWR Recomm Rep. 2006;55(RR-14):1-17.

10. 10 Hader, S, 16th CROI 2009; 57 Washington DC HIV Testing Expansion: Earlier Diagnosis Helps Identify HIV+ People at Higher CD4+ Counts  Expanding HIV testing in jails, schools, needle exchange, and couples services  Through these efforts they were able to increase the number of tests given from 43,271 tests done in 2007 to 72,864 tests done in 2008 (68.4% increase)  In addition, they were able to find patients with higher CD4 counts at initial testing –2004 – 198 cells/mm 3 –2007 – 332 cells/mm 3 Year of HIV Diagnosis Median CD4 Count 215 183 187 198 220 262 332 0 50 100 150 200 250 300 350 2001200220032004200520062007 Median CD4 Count at Time of Testing

11. Indicator Disease-guided testing for HIV 1.Why more testing ? 2.No rules vs. opt-out policy 3.Indicator disease-guided testing 4.How to identify indicator diseases 5.The HIV in Europe initiative on inidicator disease-guided testing for HIV 6.How to implement the recommendations

12. Indicator Disease-guided testing for HIV 2. Indicator disease-guided testing The ‘HIV in Europe’ Conference (2007) recommended further development of focused HIV testing in patients presenting with certain clinical conditions and/or diseases (i.e. the indicator disease testing guidelines). Cost effectiveness analysis suggests cost savings if a population with a HIV prevalence of 1% or more are tested although this rate may be as low as 0.1%.

13. Indicator Disease-guided testing for HIV 2. Indicator disease-guided testing AIDS indicator events (former CDC-C category) prevalence of HIV infection is high indication for HIV testing is obvious, but …..

14. 14 HIV Screening by Potential AIDS Defining Event in a Privately Insured US Population Potential AIDS Defining Event NScreening Rate Burkitt’s or immunoblastic lymphoma or primary lymphoma of brain 2,9803.0% Encephalopathy 2,0665.0% Invasive cervical cancer 9584.4% Candidiasis of bronchi, trachea, lung, or esophagus 5427.0% Histoplasmosis, disseminated or extrapulmonary 3702.2% Wasting /Cachexia 3504.3% Disseminated herpes or herpes meningitis 9413.8% M. avium or M. kansasii, disseminated or extrapulmonary 6713.4% Pneumocystis carinii pneumonia 4810.4% Kaposi's sarcoma 358.6% Progressive multifocal leukoencephalopathy 200.0% CMV pneumonia or retinitis 1625.0% Coccidioidomycosis, disseminated or extrapulmonary 137.7% Cryptococcosis, extrapulmonary 119.1% Misc (toxoplasmosis of brain, chronic isosporiasis, salmonella septicemia, chronic cryptosporidosis) 520.0% Chen JY, CROI 2009; 1044 Review of 8 US Health Plans - 7,451 patients  4.3% Patients Screened for HIV with Any Potential AIDS Defining Event  12.5% Patients Screened for HIV with Multiple Potential AIDS Defining Events

15. Indicator Disease-guided testing for HIV 2. Indicator disease-guided testing Additional potentially indicator diseases prevalence of HIV infection higher than general population but remain largely unknown and substantial variability HIV testing is cost-effective if prevalence of HIV infection above 0.1-1%

16. Indicator Disease-guided testing for HIV 1.Why more testing ? 2.No rules vs. opt-out policy 3.Indicator disease-guided testing 4.How to identify indicator diseases 5.The HIV in Europe initiative on inidicator disease-guided testing for HIV 6.How to implement the recommendations

17. LISTS OF PROPOSED INDICATOR DISEASES Respiratory conditions Tuberculosis Acute Respiratory Infections Esoteric Respiratory Diseases (e.g. aspergillus) Conditions Affecting the Upper and Lower Gastrointestinal Tract Oral candida Recurrent chronic bacterial diarrhoea Continued unexplained weight loss Conditions Causing Neurological Symptoms Viral meningitis Stroke-like syndrome Esoteric neurological conditions (e.g. listeria, other fungal infections, cryptococcal infections, peripheral neuropathy, Guillain-Barre Syndrome, mononeuritis multiplex) Tumours Associated with HIV Non-Hodgkin’s lymphoma Hodgkin’s lymphoma Castleman’s disease Primary effusion lymphoma Idiopathic thrombocytopenic purpura Anal cancer Other symptomatic carcinomas (e.g. cervical cancer, basal cell carcinoma, Kaposi sarcoma, melanoma, squamous cell carcinoma) Dermatological Conditions Herpes zoster Florid fungal infections Other symptomatic dermatological conditions (e.g. sebhorreic dermatitis, acne, xerosis, psoriasis, atopic dermatitis, papular pruritic eruption of HIV, erythema nodosum, molluscum contagiosum), human papilloma virus-associated warts, scabies, herpes simplex virus, staphylococcal infections) Miscellaneous Constitutional symptoms Persistent mild anaemia Persistent raised ESR HIV-related nephropathy Hepatitis B Hepatitis C STIs

18. Indicator Disease-guided testing for HIV 1.Why more testing ? 2.No rules vs. opt-out policy 3.Indicator disease-guided testing 4.How to identify indicator diseases 5.The HIV in Europe initiative on indicator disease-guided testing for HIV 6.How to implement the recommendations

19. Indicator disease surveys Aim: a survey initiative to assess HIV prevalence for one or more diseases within a segment of the population not yet diagnosed with HIV and that present for care with the specific disease/condition. Conduct: 2 phases (pilot and 2 nd ) Pilot: –25 surveys within a specific segment of the population –On consecutive patients not yet known to be HIV-infected –Have one of 8 conditions until 200 (300-400) have entered –Harmonized and central data capture Evaluation 2 nd phase

20. Pilot- Phase I 1.Sexually transmitted diseases 2.Malignant lymphoma, irrespective of type 3.Cervical or anal dysplasia or cancer, 4.Herpes zoster in a person younger than 65 years, 5.Hepatitis B or C virus infection 6.Ongoing mononucleosis-like illness 7.Unexplained leukocytopenia or thrombocytopenia lasting at least 4 weeks 8.Seborrheic dermatitis / exanthema Survey initiative to assess HIV prevalence for 8 conditions within a specific segment of the population not yet diagnosed with HIV and that present for care.

21. Timeline 2009 15 May: Call for Collaboration launched 26 June: Over 100 applications received July 2009: 17 Centres selected August-September: Ethical approval processes 21 October: First patient enrolled

22. Proposals received from the call Applications received for 103 surveys in 39 centres in 17 countries (number of applications received) 1.Sexually transmitted diseases (24) 2.Malignant lymphoma, irrespective of type (8) 3.Cervical or anal dysplasia or cancer, (5) 4.Herpes zoster in a person younger than 65 years (9) 5.Hepatitis B or C virus infection (26) 6.Ongoing mononucleosis-like illness (10) 7.Unexplained leukocytopenia or thrombocytopenia lasting at least 4 weeks (8) 8.Seborrheic dermatitis / exanthema (12)

23. Pilot- Phase I 25 surveys; 8 conditions selected for the pilot On consecutive patients not yet known to be HIV-infected Have one of the 8 conditions until 100 (200-400) patients have entered Harmonized and central data capture Following the pilot, an evaluation phase will be conducted prior to moving into Phase II

24. Review criteria for selection The criteria used for selection of the centres: Working group participant and/or Steering Committee member responsible/contact person History of collaboration/communication with centre/responsible investigator Number of patients seen per year with specific indicator disease Country representation (Western and Eastern European participation) 3-5 surveys per disease of a minimum of 100 patients Not more than 3-4 surveys per centre

25. Participating Centres by country Austria University Hospital Innsbruck, Department of Dermatology and Venereology, Inssbruck Belarus Minsk Municipal Infectious Diseases Hospital, Minsk Belgium Saint-Pierre University Hospital, Belgium Bosnia Clinical Center, University of Sarajevo, Infetious Diseases Clinic, Sarajevo Croatia University Hospital of Infectious Diseases, Zagreb Denmark Bispebjerg Hospital, København: Infektionsmedicinsk Afdeling, CESOIRS/Skejby Sygehus; Århus Germany Department of Medicine, University of Bonn, Berlin: Uniklinikum Essen, Hautklinik, Essen Italy San Paolo Hospital, Milan: STD Centre, Dermatology department, Milan Netherlands Onze Lieve Vrouwe Gasthuis, Internal Medicine, Amsterdam Poland Medical University of Bialystok, Department of Infectious Diseases, Bialystok Spain Hospital Clinic Barcelona, Infectious Diseases Unit, Barcelona Sweden Department of Infectious Diseases, Karolinska University Hospital, Stockholm UK ChelseaWestminster Hospital, London Ukraine Kharkov Regional Clinic of Infectious Diseases, Kharkov

26. Indicator disease and (# of centres) 1.Sexually transmitted diseases (5) 2.Malignant lymphoma, irrespective of type (6) 3.Cervical or anal dysplasia or cancer, (3) 4.Herpes zoster in a person younger than 65 years (5) 5.Hepatitis B or C virus infection (5) 6.Ongoing mononucleosis-like illness (5) 7.Unexplained leukocytopenia or thrombocytopenia lasting at least 4 weeks (5) 8.Seborrheic dermatitis / exanthema (5)

27. Indicator disease CRF-Form A

28. Indicator disease CRF-Form B

29. Centre decodification list

30. Indicator Disease-guided testing for HIV 1.Why more testing ? 2.No rules vs. opt-out policy 3.Indicator disease-guided testing 4.How to identify indicator diseases 5.The HIV in Europe initiative on inidicator disease-guided testing for HIV 6.How to implement the recommendations

31. 31 Recommendations for Target HIV Testing in Healthcare Settings (Indicator disease-guided)  All individuals with diseases recognized to be associated with HIV (prevalence > 0.1%) should be tested for HIV  All HCPs across Europe should be aware of the need to test more individuals for HIV  Some healthcare providers such as GPs, OBGYN, dentists, dermatologists, STD clinicians and ER physicians should particularly be targeted because they are likely to be the providers who first encounter HIV-infected patients presenting comorbid conditions  All individuals attending STD clinics should be offered an HIV test on an annual basis  European governments should consider the utility and cost-effectiveness of adopting opt-out testing for all pregnant women Gazzard B, et al. HIV Medicine (2008), 9 (Suppl. 2), 34–40

32. Considerations How do we ensure that all health systems across Europe target persons presenting with an AIDS-defining disease for HIV testing? How do we establish HIV indicator disease guided testing as appropriate standard of care across Europe? What role should HIV in Europe play in identifying the target group for information and ensuring communication to this group? What is the link between current testing policies/guidelines and indicator disease guided testing?

33. How do we ensure that all health systems across Europe target persons presenting with an AIDS- defining disease for HIV testing? In the current situation many patients with AIDS are not necessarily tested for HIV It is important to identify physician’s barrier to testing In order to achieve this, we need a Country specific analysis of non-HIV-specialised care providers involved in patients who present wth AIDS defining diseases It is important to ensure systems based on principles of human rights protection Implementation of Guidelines formulating this approach to testing and subsequent monitoring and evaluation

34. What do we mean by indicator disease? A disease indicating that a HIV test should be considered/performed AIDS defining events Diseases associated with high HIV prevalence Diseases with Implications for management Differential diagnosis

35. AIDS defining diseases Any diseases = with HIV prevalence higher than.0.1-1% Implication for the individual clinical management HIV considered for differential diagnosis PCP KS ….. ? Hepatitis ? VZV …. Cancer Transplantation …. Guillant Barré, multiple sclerosis … Strongly recommend testing Strongly recommend testing Offer testingConsider testing Indicator disease guided testing

36. How do we establish HIV indicator disease guided testing as appropriate standard of care across Europe? Current Indicator Diseases Survey will help to determine prevalence of HIV among 8 selected non- AIDS defining diseases Country-based test recommendations should be based upon Country-specific HIV prevalence of these diseases Testing for HIV has to be effective/useful in terms of all aspects of medical care including ART Widespread routine testing for less prevalent indicator diseases might require demonstration of cost- effectiveness depending on Country specific policies

37. What role should HIV in Europe play in identifying the target group for information and ensuring communication to this group? HIV in Europe should continue to assemble HIV advocates, policy makers and HIV care providers in open discussion Efforts should be made to reach a wide range of medical disciplines involved in indications for HIV testing

38. What is the link between current testing policies/guidelines and indicator disease guided testing? Standards of current testing policies to be maintained particularly while preserving human rights Indications for HIV testing will be added (see table) Any indication for HIV testing is complementary to current guidelines/policies