www.hivarca.net
� Jun 1995. The Clinical Virology Unit at the University Hospital of Siena starts low-cost HIV genotyping as a public service
� Jun 1995. The Clinical Virology Unit at the University Hospital of Siena starts low-cost HIV genotyping as a public service � Feb 2002. The clinical units are asked for their availability to integrate the sequence db with clinical data (“genotype-response”)
PHENOTYPE commercial Fold-resistance CUT-OFF providers Biological Clinical (??) (Virtual Phenotype) >20 interpretation PREDICTION systems Choice of the best regimen GENOTYPE
Fold-resistance PHENOTYPE CUT-OFF Biological Clinical (??) PREDICTION Choice of the best regimen GENOTYPE
INPUT DATA (BASELINE VARIABLES) OUTPUT DATA (RESPONSE)
INPUT DATA (BASELINE VARIABLES) OUTPUT DATA (RESPONSE)
INPUT DATA (BASELINE VARIABLES) PATIENT CASE PREDICTION (BASELINE) (RESPONSE) OUTPUT DATA (RESPONSE)
� Demographics � Therapy CLINIC � AIDS events � HBV/ HCV status LABORATORY � HIV RNA � CD4 � Genotype
� Jun 1995. The Clinical Virology Unit at the University Hospital of Siena starts low-cost HIV genotyping as a public service � Feb 2002. The clinical units are asked for their availability to integrate the sequence db with clinical data (“genotype-response”) � Jun 2002. Informa srl to provide project management and HW/SW support. GSK funding through an unrestricted educational grant
� Jun 1995. The Clinical Virology Unit at the University Hospital of Siena starts low-cost HIV genotyping as a public service � Feb 2002. The clinical units are asked for their availability to integrate the sequence db with clinical data (“genotype-response”) � Jun 2002. Informa srl to provide project management and HW/SW support. GSK funding through an unrestricted educational grant � Jan 2004. ARCA web site launched. Other units enter the network As of April 2008 CLINIC LABORATORY N = 7 0 N = 3 0
THERAPY (N = 42,596) GENOTYPE (n = 18,695) PatientID PatientID Treatment regimen Date Date of start Sequence Date of stop Method PATIENTS (n = 11,523) Reason for change/stop Subtype PatientID Resistance mutations Gender Other mutations HIV RNA (n = 145,925) Year of birth PatientID CD4 (n = 180,361) Country of origin Date PatientID Transmission route Copies/ml Date HCV status <LLD (undetectable) CD4/mmc HBV status Method CD4%
Ratio naïve / pretreated increased (now ∼ 0.2)
119 patients with ≥ 10 genotypes 509 patients with ≥ 5 genotypes No. of patients No. of follow-up genotypes
Base d o n po l subtyping o f the first available HI V-1 se que nc e fro m 10,778 patie nts (ARCA c o ho rt)
URFs Base d o n po l subtyping o f the first available HI V-1 se que nc e fro m 10,778 patie nts (ARCA c o ho rt)
Base d o n po l subtyping o f the first available HI V-1 se que nc e fro m 10,778 patie nts (ARCA c o ho rt)
Number of patients with treatment records with latest drugs
� Jun 1995. The Clinical Virology Unit at the University Hospital of Siena starts low-cost HIV genotyping as a public service � Feb 2002. The clinical units are asked for their availability to integrate the sequence db with clinical data (“genotype-response”) � Jun 2002. Informa srl to provide project management and HW/SW support. GSK funding through an unrestricted educational grant � Jan 2004. ARCA web site launched. Other units enter the network � Feb 2005. ARCA opens to external research proposals
The requesting investigator fills and posts the dedicated form The scientific board approves the proposal The proposal is unacceptable or and sends it to the ARCA centres there are insufficient data The ARCA centre agrees to The ARCA centre does not agree to share its data share its data The authorship (up to 15 authors) is established proportionally to the valid The study is performed on the cases. All the centres sharing their data but data subset from the centres not included in the authorship are given willing to share their data credits for future use (see page ‘Info’ on the ARCA web site)
21 16 12 10 9 8 7 … % n1 n2 n3 n4 n5 n6 n7 … c ase s Study1 Unit H Unit A Unit C Unit B Unit X Unit F Unit Z Unit …
Study1 (four slots) Unit c ase s % Cr e dit Unit A n1 21 0 Unit C n2 16 0 In the authorship Unit F n3 12 0 Unit H n4 10 0 Unit B n5 9 9 Unit X n6 8 8 Not in the Unit Z n7 7 7 authorship, credit gained … … … …
Study1 (four slots) Study2 (three slots) Unit c ase s % Cr e dit Unit c ase s % Unit A n1 21 Unit A n1 21 0 Unit C n2 16 0 Unit D n2 16 Unit E n3 12 Unit F n3 12 0 Unit G n4 10 Unit H n4 10 0 Unit B n5 9 Unit B n5 9 9 Unit X n6 8 8 Unit Y n6 8 Unit W n7 7 Unit Z n7 7 7 … … … … … … …
Study1 (four slots) Study2 (three slots) Unit c ase s % Cr e dit Unit c ase s % Past c r e dit Unit A n1 21 0 Unit A n1 21 0 Unit C n2 16 0 Unit D n2 16 1 Unit E n3 12 2 Unit F n3 12 0 Unit G n4 10 3 Unit H n4 10 0 Unit B n5 9 9 Unit B n5 9 9 Unit X n6 8 8 Unit Y n6 8 2 Unit W n7 7 2 Unit Z n7 7 7 … … … … … … … …
Study2 (three slots) Unit c ase s % Past c r e dit T otal Unit A n1 21 0 21 Unit D n2 16 1 17 Unit E n3 12 2 14 Unit G n4 10 3 13 Unit B n5 9 9 18 Unit Y n6 8 2 10 Unit W n7 7 2 9 … … … … …
Study2 (three slots) Unit c ase s % Past c r e dit T otal Unit A n1 21 0 21 Unit D n2 16 1 17 Unit E n3 12 2 14 Unit G n4 10 3 13 Unit B n5 9 9 18 Unit Y n6 8 2 10 Unit W n7 7 2 9 … … … … …
Study2 (three slots) Unit c ase s % Past c r e dit T otal Cr e dit Unit A n1 21 0 21 0 Unit D n2 16 1 17 0 Unit E n3 12 2 14 14 Unit G n4 10 3 13 13 Unit B n5 9 9 18 0 Unit Y n6 8 2 10 10 Unit W n7 7 2 9 9 … … … … … …
� Requests so far posted only by ARCA affiliates but being an affiliate is not necessary!! � None of the ARCA centres denied use of its own data
Targeted conferences: Eur Workshop HIV Drug Res Intl Workshop HIV Drug Res CROI MAIN DRAWBACK Most of the posters/ presentations accepted at conferences have been not translated into papers
� Jun 1995. The Clinical Virology Unit at the University Hospital of Siena starts low-cost HIV genotyping as a public service � Feb 2002. The clinical units are asked for their availability to integrate the sequence db with clinical data (“genotype-response”) � Jun 2002. Informa srl to provide project management and HW/SW support. GSK funding through an unrestricted educational grant � Jan 2004. ARCA web site launched. Other units enter the network � Feb 2005. ARCA opens to external research proposals � Jan 2006. ARCA cooperates with the major HIV resistance db’s in Germany and Sweden in the EU-funded STREP “EuResist”
Integration of viral genomics with clinical data to predict response to anti-HIV treatment (STREP) � Management Informa srl, Rome, Italy � Data providers & virology ARCA, Italy AREVIR, Germany Karolinska DB, Sweden � Data modeling Max Planck Society for the Advancement of Science, Germany Dept. Automation, Engineering, Rome III, Italy IBM Labs, Haifa, Israel RMKI, Budapest, Hungary � Supervision & peer reviewing EFPIA
� Not a trivial process! � Duplicate patients Identical CD4 count and % on the same day › › Identical sequence(s) detected via checksum � Many checking routines implemented when inserting/modifying data in the original database � Most difficult when importing data from poorly designed electronic records Most frequent problem: overlapping therapies › � Progressively reduced to ∼ 2% › Most challenging quality check: sequences � Formats, base mixtures, stop codons, frameshifts Conservative strategy: get rid of uncertain data!
The ARCA server periodically generates and send tables with “suspicious” data Flagged and not Flagged and included in included in future inquiries future inquiries The ARCA Monitor interacts with the original clinic/ lab and tries to fix the issues Issue declared Issue still not solvable pending Issue solved
� Jun 1995. The Clinical Virology Unit at the University Hospital of Siena starts low-cost HIV genotyping as a public service � Feb 2002. The clinical units are asked for their availability to integrate the sequence db with clinical data (“genotype-response”) � Jun 2002. Informa srl to provide project management and HW/SW support. GSK funding through an unrestricted educational grant � Jan 2004. ARCA web site launched. Other units enter the network � Feb 2005. ARCA opens to external research proposals � Jan 2006. ARCA cooperates with the major HIV resistance db’s in Germany and Sweden in the EU-funded STREP “EuResist” � Sep 2006. Support from the main antiretroviral drug companies (statistics section)
Financial support for: •HW & SW maintenance •Data entry and cleansing •Opportunities for young investigators (coming soon) � Travel grants � ARCA fellowship/ award
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