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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)
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)
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
IAS 2011, ANRS satellite symposium “HIV-2: A model of attenuated HIV Infection”, 19 July
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
IAS 2011, ANRS satellite symposium “HIV-2: A model of attenuated HIV Infection”, 19 July
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?
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 HI V Epidemiological Research Europe Coordination: Copenhagen HIV Programme (CHIP) & Institut de Santé Publique,d'Epidémiologie et de Développement (ISPED)
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 HI V 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
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)
IAS 2011, ANRS satellite symposium “HIV-2: A model of attenuated HIV Infection”, 19 July
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
IAS 2011, ANRS satellite symposium “HIV-2: A model of attenuated HIV Infection”, 19 July
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
IAS 2011, ANRS satellite symposium “HIV-2: A model of attenuated HIV Infection”, 19 July
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
IAS 2011, ANRS satellite symposium “HIV-2: A model of attenuated HIV Infection”, 19 July
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
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. Pierre
Collaboration of Observational HI V Epidemiological Research Europe Coordination: Copenhagen HIV Programme (CHIP) & Institut de Santé Publique,d'Epidémiologie et de Développement (ISPED)
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. Pierre
Collaboration of Observational HI V 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
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
IAS 2011, ANRS satellite symposium “HIV-2: A model of attenuated HIV Infection”, 19 July
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
IAS 2011, ANRS satellite symposium “HIV-2: A model of attenuated HIV Infection”, 19 July
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)