HIV-1 and HIV-2 diagnostics AREVIR, Kln 11.04.2013 How different - - PowerPoint PPT Presentation

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HIV-1 and HIV-2 diagnostics AREVIR, Kln 11.04.2013 How different are they? 1, 2, 3 Phylogenetic view of immune deficiency viruses Nomenclature of HIV: types, groups and subtypes type HIV-1 group M- 1983 P -2009 N -1998 O -1994

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HIV-1 and HIV-2 diagnostics

AREVIR, Köln 11.04.2013

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How different are they? 1, 2, 3…

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Phylogenetic view of immune deficiency viruses

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Nomenclature of HIV: types, groups and subtypes

A B/D C F G H J K

HIV-1 M-1983 N-1998 O-1994

A B C D E F G H

HIV-2, 1985

type group subtype I II III IV V VI type group

HIV unknown

P-2009

A1,A2

stolen from Lutz Gürtler

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Forests and distribution of sooty mangabey monkeys (Cercocebus atys) and HIV-2 in West-Africa

Modified from Lutz Gürtler HIV-2 Forests and sooty mangabey

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Prevalence of HIV-2 groups in West-Africa: A and B in all countries, India only HIV-2:A, USA

180 cases

Cap Verde Island

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Epidemiology of HIV-2

 Mainly in West-Africa  But also in countries

associated to West- Africa

 in Portugal, HIV-2

causes 4.5% of AIDS cases

 in France, 1.8% of new

HIV diagnoses between 2003 and 2006 by HIV-2

 …

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HIV diagnosis - methods

 4th generation screening ELISA detect  antibodies against HIV-1/2  HIV-1 p24 antigen  Confirmation by immunoblot  Usually specific for HIV-1 or HIV-2  Not covering p24 component of screening  Validation of a 2-rapid-test system ?

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HIV-2 diagnostic – different-2 ?

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Western blot – specific?

 There is substantial antibody cross-reactivity  There are HIV-1 immunoblots including a specific HIV-2 band

BUT is there co-infection of HIV-1/2 ?

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How to detect HIV-2 definitely ?

 Reactive HIV screening test needs

confirmation by

 Immunoblot  A second independant sample  Nucleid acid testing for HIV-1

First viral load

 Nucleid acid testing for HIV-2 ?

Independent proof by viral component

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HIV2EU collaboration Resistance algorithm

HIV Genotypischer Resistenzalgorithmus Deutschland

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M. Obermeier 5/2012

HIV2EU publication

Charpentier, Charlotte, Ricardo Camacho, Jean Ruelle, Rolf Kaiser, Josef Eberle, Lutz Gürtler, Alejandro Pironti, Martin Stürmer, Françoise Brun-Vézinet, und Diane Descamps. „HIV-2EU-Supporting Standardized HIV-2 Drug Resistance Interpretation in Europe“. Clinical Infectious Diseases (2013). http://cid.oxfordjournals.org/content/early/2013/02/19/cid.cit104.short.

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M. Obermeier 5/2012

HIV-2 sequences from Los Alamos National Laboratories in the HIV-GRADE tool

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M. Obermeier 5/2012

Basis of the HIV-GRADE internet-tool

 HIV-Alg module from Stanford-HIVdb  PERL-source-code is freely available  Software is in development since

1999

 Algorithm Specification Interface (ASI)

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M. Obermeier 5/2012

Algorithm Specification Interface (ASI)

 Rule-based algorithms can be

described using xml-syntax

 Xml-Files available for Stanford-

HIVdb, ANRS and REGA HIV-GRADE can be described in a compatible format.

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M. Obermeier 5/2012

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M. Obermeier 5/2012

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M. Obermeier 5/2012

Workflow HIV2EU

Sequence data Mutation list

Identification of available genes Alignment on Pan- Genotype Consensus Identification of mutations

Analysis of mutations based on the algorithm Detailled output Tabular output

Identification of genotype and re-alignment on group specific consensus-sequence

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M. Obermeier 5/2012

HIV-2 tropism mutations

Visseaux, B., M. Hurtado-Nedelec, C. Charpentier, G. Collin, A. Storto, S. Matheron, L. Larrouy, u. a. „Molecular Determinants of HIV-2 R5-X4 Tropism in the V3 Loop: Development of a New Genotypic Tool“. Journal of Infectious Diseases 205, Nr. 1 (2. Dezember 2011): 111–120. doi:10.1093/infdis/jir698.

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M. Obermeier 5/2012

German HIV-2 testing and treatment guidelines

 HIV-GRADE and HIV2EU team were

asked by the DAIG

 Diagnostic guidance  Treatment guidance

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M. Obermeier 5/2012

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HIV-GRADE association

 Thomas Berg, Medizinisches Labor Dr. Berg, Berlin  Patrick Braun, PZB, Aachen  Martin Däumer, Institut für Virologie, Köln  Josef Eberle, Pettenkofer-Institut, München  Robert Ehret, PZB Aachen  Rolf Kaiser, Institut für Virologie, Köln  Klaus Korn, NRZ für Retroviren, Erlangen  Claudia Kücherer, Robert Koch Institut, Berlin  Harm Müller,Labor Fenner, Hamburg  Christian Noah, Labor Lademannbogen, Hamburg  Martin Stürmer, Institut für Medizinische Virologie, Frankfurt  Alexander Thielen, Max Planck Institut Saarbrücken  Hauke Walter, NRZ für Retroviren, Erlangen

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M. Obermeier 5/2012

HIV2EU group

 Charlotte Charpentier  Ricardo Camacho  Jean Ruelle  Rolf Kaiser  Josef Eberle  Lutz Gürtler  Alejandro Pironti  Martin Stürmer  Françoise Brun-Vézinet  Diane Descamps  Martin Obermeier