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. 2015;1(3):134-139.
doi: 10.1016/S2055-6640(20)30510-0. Epub 2015 Jun 30.

The EPIICAL project: an emerging global collaboration to investigate immunotherapeutic strategies in HIV-infected children

P Palma  1 , C Foster  2 , P Rojo  3 , P Zangari  4 , A Yates  5 , N Cotugno  4 , N Klein  6 , K Luzuriaga  7 , S Pahwa  8 , E Nastouli  9 , D M Gibb  10 , W Borkowsky  11 , S Bernardi  1 , V Calvez  12 , E Manno  4 , Nadia Mora  1 , A Compagnucci  13 , B Wahren  14 , Má Muñoz-Fernández  15 , A De Rossi  16 , J Ananworanich  17 , D Pillay  18 , C Giaquinto  19 , P Rossi  4
Affiliations

The EPIICAL project: an emerging global collaboration to investigate immunotherapeutic strategies in HIV-infected children

P Palma et al. J Virus Erad. 2015.

Abstract

The EPIICAL (Early-treated Perinatally HIV-infected Individuals: Improving Children's Actual Life with Novel Immunotherapeutic Strategies) project arises from the firm belief that perinatally infected children treated with suppressive antiretroviral therapy (ART) from early infancy represent the optimal population model in which to study novel immunotherapeutic strategies aimed at achieving ART-free remission. This is because HIV-infected infants treated within 2-3 months of life have a much reduced viral reservoir size, and rarely show HIV-specific immunity but preserve normal immune development. The goal of EPIICAL is the establishment of an international collaboration to develop a predictive platform using this model to select promising HIV therapeutic vaccine candidates, leading to prioritisation or deprioritisation of novel immunotherapeutic strategies. To establish this platform, the EPIICAL Consortium aims to: develop predictive models of virological and immunological dynamics associated with response to early ART and to treatment interruption using available data from existing cohorts/studies of early-treated perinatally HIV-infected children; optimise methodologies to better characterise immunological, virological and genomic correlates/profiles associated with viral control; test novel immunotherapeutic strategies using in vivo proof-of-concept (PoC) studies with the aim of inducing virological, immunological and transcriptomic correlates/profiles equivalent to those defined by the predictive model. This approach will strengthen the capacity for discovery, development and initial testing of new therapeutic vaccine strategies through the integrated efforts of leading international scientific groups, with the aim of improving the health of HIV-infected individuals.

Keywords: HIV; children; early treated; immunotherapies; therapeutic vaccines.

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Figures

Figure 1.
Figure 1.
Reasons for the urgent need for new therapeutic strategies for vertically HIV-infected children
Figure 2.
Figure 2.
The unique features of early-treated children as a model. The panel summarises the main differences among early-treated children and other model populations. HIV-infected infants treated within 2–3 months of life rarely exhibit HIV-specific immunity, have a more limited viral reservoir and viral diversity, greater thymic output, lower numbers of central memory T cells and greater ability to develop and maintain protective responses to vaccination, compared with other population models
Figure 3.
Figure 3.
Cohorts/studies of early-treated HIV-infected children around the world (both observational cohorts and clinical trials cohorts) that are available to generate correlates/profiles of viral control after treatment initiation and interruption
Figure 4.
Figure 4.
(a) Immunological and virological data as well as the transcriptomic correlates/profiles of infants who rapidly controlled (large retrospective cohorts/studies) and controlled (prospective cohorts/studies) viral replication both in response to therapy initiation and to treatment will provide the correlates/profiles of good or poor viral controllers.(b) The ability of an immunotherapeutic strategy to reproduce such correlates/profiles will be at the basis of the in vitro and in vivo predictive platform.
Figure 5.
Figure 5.
The EPIICAL roadmap to the development of an effective therapeutic HIV vaccine
See this image and copyright information in PMC

References

    1. UNAIDS UNAIDS Report on the Global AIDS Epidemic 2013. 2013. Available at: www.unaids.org/en/media/unaids/contentassets/documents/epidemiology/2013... ( accessed June 2015).
    1. Persaud D, Gay H, Ziemniak C et al. . Absence of detectable HIV-1 viremia after treatment cessation in an infant. N Engl J Med 2013; 369: 1828– 1835. - PMC - PubMed
    1. Saez-Cirion A, Bacchus C, Hocqueloux L et al. . Post-treatment HIV-1 controllers with a long-term virological remission after the interruption of early initiated antiretroviral therapy ANRS VISCONTI Study. PLoS pathogens 2013; 9: e1003211. - PMC - PubMed
    1. Giacomet V, Vigano A, Erba P et al. . Unexpected vertical transmission of HIV infection. Eur J Pediatr 2014; 173: 121– 123. - PubMed
    1. Butler KM, Gavin P, Coughlan S et al. . Rapid viral rebound after 4 years of suppressive therapy in a seronegative HIV-1 infected infant treated from birth. Pediatr Infect Dis J 2015: 34: e48– 51. - PubMed

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