EACS guidelines in the context of the HIV epidemiology in Europe

Jürgen RockstrohDepartment of Medicine I, University of Bonn, Bonn, Germany

EACS guidelines• EACS produces the European Guidelines for

treatment of HIV infected adults in Europe. So far the treatment guidelines have been translated from English into 13 additional languages.

• All diffferent versions in all languages are free dowloadable from the eacs website:– http://www.europeanaidsclinicalsociety.org

Table of contents

EACS guidelines: When to start• Initiation of ART

– ART is always recommended if CD4 count <350 cells/mm3

– Serodiscordant couples: Early ART should be considered and actively discussed

Adapted from EACS Guidelines. Version 6; Oct 2011. Available at: www.europeanaidsclinicalsociety.org. Accessed June 2012

ConditionCurrent CD4 + lymphocyte count

350-500 >500

Asymptomatic HIV infection C D

Symptomatic HIV disease (CDC B or C conditions) incl. tuberculosis R R

Primary HIV infection C C

Pregnancy (before third trimester) R R

Conditions (likely or possibly) associated with HIV, other than CDC stage B or C disease:

HIV-associated kidney disease R R

HIV-associated neurocognitive impairment R R

Hodgkin's lymphoma R R

HPV-associated cancers R R

Other non-AIDS-defining cancers requiring chemo- and/or radiotherapy C C

Autoimmune disease — otherwise unexplained C C

High risk for CVD (>20% estimated 10-yr risk) or history of CVD C C

Chronic viral hepatitis

HBV requiring anti-HBV treatment R R

HBV not requiring anti-HBV treatment C/R D

HCV for which anti-HCV treatment is being considered or given R D

HCV for which anti-HCV treatment not feasible R C

C, CONSIDER; D, DEFER; R, RECOMMENDED

Type 2 diabetes: diagnosis and management

Fasting plasma glucose mmol/L (mg/dL) (ii)

Oral glucose tolerance test (OGTT) 2-h value mmol/L (mg/dL) (iii)

HbA1c (iv)

Diabetes ≥7.0 (126) OR → ≥11.1 (200) ≥6.5%

Impaired glucose tolerance (IGT)

<7.0 (126) AND → 7.8–11.0 (140–199) Prediabetes 5.7–6.4%

Impaired fasting glucose (IFG)

5.7–6.9 (100–125) <7.8 (140)

i As defined by WHO and International Diabetes Federation (2005)ii An abnormal finding should be repeated before confirming the diagnosisiii Recommended in patients with fasting blood glucose 5.7–6.9 mmol/L (100–125 mg/dL) as it may identify patients with overt diabetesiv Do not use HbA1c in presence of haemoglobinopathies, increased erythrocyte turnover and sever liver or kidney dysfunction. Falsely high values are measures under supplementation with iron, vitamin C and E as well as older age (age >70: HbA1c +0.4%)Both IGT and IFG increase CV morbidity and mortality, and increase the risk of developing diabetes by 4–6 fold. These patients should be targeted for lifestyle intervention, and their CV risk factors must be evaluated and treated

EACS guidelines 2011; 1:1–61.

Diagnostic criteria (i)

EACS guidelines 2011; 1:1–61.

If modification of lifestyle measures is insufficient

Metformin• Always to be considered as the first oral agent (i)

• Start dose (500–700 mg qd), increase to max tolerated dose of 2(-3) g/d in 4– weeks

• (May worsen lipoatrophy)

Sulfonylureas• May be considered for non-overweight if

glucose is very high• No clinical trial in HIV +ve patients

HbA1c > 6.5–7%

Use a combination of 2 oral agents (i)

(metformin/sulfonylurea/incretine/exenatide)

HbA1c > 6.5–7%

Refer to specialist use insulin

Management of patients with diabetesTreatment goals: glucose control (Hb1Ac <6.5–7% without hypoglycaemia, fasting plasma glucose 4–6 mmol/L (73–110 mg/dL)• Normal blood lipids and blood pressure<130/80 mmHg (see p. 31 and p. 27)• Acetylsalicylic acid (75–150 mg/d) considered in diabetes with elevated underlying CVD risk (see p. 26)• Nephropathy, polynephropathy and retinopathy screening should be performed as in diabetic patients without HIV• Consultation with a speciality in diabetology is recommended

i Very limited data for incretines (e.g. liraglutide, saxagliptine, sitagliptine, vildagliptine) and exenatide in HIV patients; no clinically significant drug-to-drug interaction expected; clinical use of pioglitazone questioned by its side effects

Interventions for Treatment of Diabetes

Prevalence of hepatitis C in the HIV population (1960/5957 patients = 33%)

Rockstroh et al. J Inf Dis 2005;192:992–1002

South: 695 = 41.4 %

North: 359 = 23.2 %

Central: 293 = 19.6 %

East: 613 = 46.9 %

Regions:SouthCentralNorthEast

Acute HCV among HIV+ MSM

1:Luetkemeyer JAIDS 2006; 2:Cox Gastroenterology 2008; 3:Giraudon Sex Transm Infect 2008; 4:Ruf Eurosurveill 2008; 5:Vogel CID 2009; 6:Gambotti Euro Surveill 2005; 7:Morin Eur J Gastro Hepat 2010; 8:Urbanus AIDS 2009; 9:Rauch CID 2005; 10:Gallotta 4th Works. HIV & Hep. Coinf. 2008; 11:Matthews CID 2009; 12:Sherman CID 2002; 13:Backus JAIDS 2005; 14:UNAIDS Report 2008; 15:Soriano JID 2008; 16:Matthews CID 2011; 17:Arends Neth J Med 2011; 18:Neukam HIV Med 2011; 19:Pfafferott PLoS One 2011; 20:Bottieau Euro Surveill 2010; 21:Barfod Scand JID 2011; 22:Dionne-Odom Lancet Infect Dis 2009; 23:Taylor Gastroenterology 2009; 24:Hull personal conversation 2011; 25:Remis 1st Canadian HCV Conference 2001; 26:UNGASS Country progress Report 2010; 27:Soriano personal conversation 2011; 28:Boesecke 18thCROI Boston 2011 abstract #113; 29:Sun Liver International 2011; 30:Lee J F Med Assoc 2008

Australia11: 47 casesPrevalence chronic HCV/HIV16,19

< 1%: 1.000

USA1,2: 55 casesPrevalence chronic HCV/HIV12-14

15 – 30%: 180.000 – 360.000

Europe: 1068 casesPrevalence chronic HCV/HIV14,15

25%: 185.500

-UK3,4 552-Germany5,18, 28 157-France6,7 126-Netherlands8,17 97-Belgium20 69-Swiss9 23-Italy10 21-Denmark21 13-Spain27 ~8

Lebanon22: 1 casePrevalence chronic HCV/HIV26

49%: 1.500

Canada24: ~30 casesPrevalence chronic HCV/HIV25

19%: 11.200

Taiwan29: 30 casesPrevalence chronic HCV/HIV30

55%: 8.800

Algorithm for management of acute HCV in HIV-infected individuals

EACS guidelines 2011; NEAT Acute Hepatitis C Infection Consensus Panel. AIDS 2011:25;399-409

New Treatment Options for HIV/HCV Genotype 1 Patients: EACS Guidelines

• EACS guidelines include the option to treat HIV/HCV GT 1 coinfected patients with telaprevir*[1]

• Updated guidelines will also include option to treat with boceprevir as interim results became available

*With efavirenz, telaprevir dose should be increased to 1150mg every 8 hours. Data on coadministration of telaprevir with raltegravir is anticipated, but clinicians are advised to check www.hep-druginteractions.com for further information.

1. EACS Guidelines, October 2011, Version 6.0.

Newly diagnosed chronic HCV GT 1 infection

F2F3aF0F1a F4a

In general, treatment can be deferred. Consider treatment with Peg/RBV and an HCV protease inhibitor or Peg/RBV alone if low HCV viral load, IL28B CC genotype, absence of insulin resistance and high CD4+ cell count.

Treatment with Peg/RBV and an HCV protease inhibitor.

Treatment with Peg/RBV and an HCV protease inhibitor if compensated disease. Treatment should be undergone in specialised centres.

Management of newly diagnosed HIV-HCV coinfected genotype-1 patients

Perform transient elastography and/or serum marker and/or liver biopsy

aMetavir fibrosis score: F0=no fibrosis; F1= portal fibrosis, no septae; F2= portal fibrosis, few septae, F3=bridging fibrosis, F4=cirrhosis.

Management of Newly Diagnosed HIV/HCV Coinfected Genotype 1 Patients

Ingiliz P, Rockstroh. J. Liver International 2012

EACS guidelines• Reflect the different regulatory and economic

treatment scenarios in Europe• Are based on “treatment has to benefit the

individual”• Attempt to improve management of

concomitant comorbidities• Provide guidance on management of viral

hepatitis coinfection– http://www.europeanaidsclinicalsociety.org

Come and visit the EACS booth 116 in hall D