indicator diseases guided-testing for hiv antonella d´arminio monforte jose m gatell

Indicator Diseases guided-testing for HIV

Antonella d´Arminio Monforte

Jose M Gatell

Indicator Disease-guided testing for HIV

1. Why more testing ?2. No rules vs. opt-out policy3. Indicator disease-guided testing4. How to identify indicator diseases5. The HIV in Europe initiative on

inidicator disease-guided testing for HIV

6. How to implement the recommendations

CD4 count at start of ART, 2003-2005 42 countries, 176 sites, 33,008 patients

187

181

159

87

97

12286

100125

123

97

239

10353

72

192163

206157

134

102

200179

95

CROI 2007 – CD4 at start – 10

164

Numbers are median CD4 counts

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

Estimation of the new annual infections for sexual Estimation of the new annual infections for sexual transmission between carriers of HIVtransmission 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 +

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.

10Hader, 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/mm3

– 2007 – 332 cells/mm3

Year of HIV Diagnosis

Med

ian

CD

4 C

ou

nt

215

183 187198

220

262

332

0

50

100

150

200

250

300

350

2001 2002 2003 2004 2005 2006 2007

Median CD4 Count at Time of Testing


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%.


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

HIV Screening by Potential AIDS Defining Event in a Privately Insured US Population

Potential AIDS Defining Event N Screening Rate

Burkitt’s or immunoblastic lymphoma or primary lymphoma of brain 2,980 3.0%

Encephalopathy 2,066 5.0%

Invasive cervical cancer 958 4.4%

Candidiasis of bronchi, trachea, lung, or esophagus 542 7.0%

Histoplasmosis, disseminated or extrapulmonary 370 2.2%

Wasting /Cachexia 350 4.3%

Disseminated herpes or herpes meningitis 94 13.8%

M. avium or M. kansasii, disseminated or extrapulmonary 67 13.4%

Pneumocystis carinii pneumonia 48 10.4%

Kaposi's sarcoma 35 8.6%

Progressive multifocal leukoencephalopathy 20 0.0%

CMV pneumonia or retinitis 16 25.0%

Coccidioidomycosis, disseminated or extrapulmonary 13 7.7%

Cryptococcosis, extrapulmonary 11 9.1%

Misc (toxoplasmosis of brain, chronic isosporiasis, salmonella septicemia, chronic cryptosporidosis) 5 20.0%

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


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%

LISTS OF PROPOSED INDICATOR DISEASESRespiratory 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


1. Why more testing ?2. No rules vs. opt-out policy3. Indicator disease-guided testing4. How to identify indicator diseases5. The HIV in Europe initiative on indicator

disease-guided testing for HIV6. How to implement the

recommendations

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 2nd)

• 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• 2nd phase

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.

Timeline 2009

15 May: Call for Collaboration launched26 June: Over 100 applications receivedJuly 2009: 17 Centres selectedAugust-September: Ethical approval processes 21 October: First patient enrolled

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)

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

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

Participating Centres by countryAustria University Hospital Innsbruck, Department of Dermatology and Venereology, InssbruckBelarus Minsk Municipal Infectious Diseases Hospital, MinskBelgium Saint-Pierre University Hospital, BelgiumBosnia Clinical Center, University of Sarajevo, Infetious Diseases Clinic, SarajevoCroatia University Hospital of Infectious Diseases, ZagrebDenmark Bispebjerg Hospital, København: Infektionsmedicinsk Afdeling, CESOIRS/Skejby Sygehus;

ÅrhusGermany Department of Medicine, University of Bonn, Berlin: Uniklinikum Essen, Hautklinik, EssenItaly San Paolo Hospital, Milan: STD Centre, Dermatology department, MilanNetherlands Onze Lieve Vrouwe Gasthuis, Internal Medicine, AmsterdamPoland Medical University of Bialystok, Department of Infectious Diseases, BialystokSpain Hospital Clinic Barcelona, Infectious Diseases Unit, BarcelonaSweden Department of Infectious Diseases, Karolinska University Hospital, StockholmUK ChelseaWestminster Hospital, LondonUkraine Kharkov Regional Clinic of Infectious Diseases, Kharkov

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)

Indicator disease CRF-Form A

Indicator disease CRF-Form B

Centre decodification list

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

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?

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

What do we mean by indicator disease?

A disease indicating that aHIV test should be considered/performed

AIDS defining events

Diseases associated

with high HIV prevalence

Diseases with Implications

for management

Differential diagnosis

AIDS defining diseases

Any diseases = with HIV prevalence higher than.0.1-1%

Implication for the individual clinicalmanagement

HIV considered for differential diagnosis

PCPKS…..

? Hepatitis? VZV….

CancerTransplantation….

Guillant Barré, multiple sclerosis…

Strongly recommendtesting

Strongly recommendtesting

Offer testing Consider testing

Indicator disease guided testing

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

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

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

indicator diseases guided-testing for hiv antonella d´arminio monforte jose m gatell

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