achi e v2 e, cohere & eurocoord added value of collaborative studies geneviève chêne inserm...

ACHIEV2E, COHERE & EuroCoord

Added value of collaborative studies

Geneviève ChêneInserm U897, Bordeaux Segalen University

I MI T AMACS ECS-Mothers & ECS- I nfants NSHPC-Mothers & NHPS- I nfants PI SCI S

KOMPNET CASCADE ANRS CO2 SEROCO Frankfurt HI V Cohort Study San Raff aele

ANRS CO1/ CO10 EPF UK CHI C Athena I TLR-Mothers & I TLR-I nfants Swiss HI V Cohort Study

I CC ANRS CO6 PRI MO Co-RI S MOCHI V-Mothers & MoCHI V-I nfants The I talian MASTER Cohort

CHI PS ANRS CO4 French Hospital’s Database on HI V HI V-MI P-Mothers & HI V-MI P-I nfants

GEMES-Haemo ANRS CO3 AQUI TAI NE EuroSI DA Madrid Cohort HI V Children VACH

Modena Cohort Study Danish HI V Study ANRS CO 8 COPI LOTE I CONA St. P ierre

Collaboration of Observational HIV Epidemiological Research Europe Coordination: Copenhagen HIV Programme (CHIP) & Institut de Santé Publique,d'Epidémiologie et de Développement (ISPED)








Collaboration of Observational HIV Epidemiological Research Europe Coordination: Copenhagen HIV Programme (CHIP) & Institut de Santé Publique,d'Epidémiologie et de Développement (ISPED)

IAS 2011, ANRS satellite symposium “HIV-2: A model of attenuated HIV Infection”, 19 July

Main features of HIV2 Occur mainly in West Africa, though growing

numbers in Europe, India and the US Low transmissibility HIV2 RNA undetectable even at late stages, slow CD4

decline, slow immuno-clinical progression Intrinsically resistant to some commonly used classes

for antiretroviral treatment Poor CD4 recovery once treatment is started


Main challenges for HIV2

Are natural history of HIV1 & HIV2 so different? How best to quantify the virus? How best to monitor treatment response? What endpoint should be used in clinical trials? When to start treatment? What to start with?

Use of collaborative studies• Power, representativeness• Potential for standardisation• Comparisons with HIV1


Rationale of collaborative studies on HIV2: examples

Need for standardisation• Establish a standard to quantify HIV2 RNA

What to start with?• Compare different first-line regimens

Comparisons with HIV1• Are HIV1 and HIV2 characterised by different CD4 cell

decline at any HIV RNA levels?








Collaboration of Observational HI V Epidemiological Research Europe Coordination: Copenhagen HIV Programme (CHIP) & Institut de Santé Publique,d'Epidémiologie et de Développement (ISPED)










HIV2 RNA quantification, quality control: lessons learned

Feasible: 12 labs participating in 3 continents (Europe, Africa, North America)

Different situations for subtypes• Use of a standard improved quantification of subtype A• Remaining heterogeneity in the quantification of subtype B

virus, even with the use of a standard, collaborations needed across countries where subtype B is circulating

Comparisons difficult when subtype B involved Commercial kit warranted, control quality needed

Damond et al. J Clin Microbiol 2008, 2011 (revised)


170 naive HIV2 patients started on either PI/r or 3 nucs, 7 European cohorts

Standardisation of data collection through the HICDEP system commonly used for collaborations on HIV1

Potential of 1,000 HIV2 patients/250 treatment-naiveInform the design of clinical trials

Benard et al. Clin Infect Dis 2011


Virus type N BaselineCD4/µl

Baseline viral load

CD4 decline (annual rate)

1 120 458 4.3 15.9%

2 49 618 1.3 4.1%

Individuals seen on at least 3 occasions, during ≥ 1 year, baseline CD4+ T cell > 200/µlMean follow-up ~3 years

Plasma HIV RNA higher in HIV1 than HIV2 despite similar rates of DNASimilar rate of CD4 decline after adjustment for baseline HIV2 RNA

Gottlieb et al. J Infect Dis 2002


Virus type N BaselineCD4/µl

Baseline viral load

CD4 decline (annual rate)

Sero-incident

1 98 399 4.11 -49

2 49 585 2.40 -9

Seroprevalent*

1 320 324 4.39 -49

2 160 260 2.62 -11

After ARV Before 2M/after

1 59 277 4.64 +59/+46

2 63 267 2.92 +29/-3

ANRS CO3 Aquitaine and CO5 HIV-2

*Difference remaining after adjustment for baseline HIV RNA or CD4

Drylewicz et al. AIDS 2008


Collaboration with COHERE in EuroCoord

EU-funded NoE established by several of the biggest HIV-1 cohorts and collaborations within Europe

35 cohorts, 30 countries

~250,000adults, mothers, children







Modena Cohort Study Danish HI V Study ANRS CO 8 COPI LOTE I CONA St. Pierre








Modena Cohort Study Danish HI V Study ANRS CO 8 COPI LOTE I CONA St. Pierre



Investigating the lower pathogenicity of HIV-2,COHERE in EuroCoord/ACHIEVE

• Project lead: S Matheron, Statistician: R Thiébaut• Objective: to compare immunological outcome in HIV-1 and

HIV-2 infected patients while controlling for plasma HIV RNA in three different populations– Natural history (absence of antiretroviral therapy)

– seroincident patients (known/estimated date infection)– seroprevalent patients

– Response to first line cART– Largest possible sample size, longitudinal design, comparison to

matched HIV1 individuals, most recent and potent ARV• Outcomes: CD4 slopes adjusted for plasma HIV RNA in HIV-1

and HIV-2 infected patients presenting similar characteristics at inclusion or cART initiation

• Timelines: data merger end July 2011, preliminary results March 2012


Perspectives Results inform the design of clinical trials (standardised

quantitative viral load, composite outcome, rate of progression) and ongoing collaborations

Exploit the infrastructures of international consortium of longitudinal studies Census of available biobank (Achieve, EuroCoord) Drug resistance: comparison of preferred pathways

between HIV1 & HIV2 (CHAIN) Models of clinical progression, when to start (ART-

CC, IeDEA) Need to identify specific funding for this research


AcknowledgmentsTo the patients, to the funder of ACHIEVE: Agence Nationale de

Recherches sur le Sida et les hépatites virales (ANRS)

To the ACHIEV2E collaborationClinical centresFrance: Sophie MATHERON

Germany: Jürgen ROCKSTROH,

Carolynne SCHWARZE-ZANDER

Netherlands: Frank DE WOLF

Ard van SIGHEM , Peter REISS

Maarten SCHIM VAN DER LOEFF

Portugal: Francisco ANTUNES*

Emilia VALADAS

Kamal MANSINHO

Spain: Vicente SORIANO*

Ana TREVINO

Carlos TORO

Berta RODES

Switzerland: Jürg BÖNI

Martin RICKENBACH

Alexandra CALMY

UK: Jane ANDERSON

Jennifer TOSSWILL

LaboratoriesBelgium: Patrick GOUBAU ,

Jean RUELLE

Canada: Marc WAINBERG

France: Brigitte AUTRAN

Françoise BRUN-VEZINET

Florence DAMOND*, Diane DESCAMPS

François SIMON

Gambia: Akum AVEIKA, Matthew COTTEN

Sarah ROWLAND-JONES

Germany: Bernd KUPFER

Italy: Claudia BALOTTA

Carlo TORTI

Netherlands: Martin SCHUTTEN

Portugal: Vitor DUQUE, Joao VAZ

Ricardo CAMACHO , Perpetua GOMES

Sweden: Jan ALBERT

USA: Geoffrey GOTTLIEB

UK: Deenan PILLAY, Bridget FERNS, Jeremy GARSON

Coordinating centre, INSERM U897France: Antoine BENARD

Geneviève CHENE

Audrey TAIEB

COHERE (www.cohere.org) and EuroCoord (www.EuroCoord.net)

achi e v2 e, cohere & eurocoord added value of collaborative studies geneviève chêne inserm...

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