EPIICAL

17

Dec, 2021

Size of HIV-1 reservoir is associated with telomere shortening and immunosenescence in early-treated European children with perinatally acquired HIV-1

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Authors: A Dalzini, G Ballin, S Dominguez-Rodriguez, P Rojo , M.R Petrara, C Foster, N Cotugno, A Ruggiero, E Nastouli, N Klein, S Rinaldi, S Pahwa, P Rossi, C Giaquinto, P Palma , A De Rossi1, and on behalf of EPIICAL Consortium

Published in: Journal of the International AIDS Society

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6

Dec, 2021

Characterisation of the HIV proviral and inducible reservoir in well- suppressed children on long-term ART

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Authors: Gärtner K, Byott M, Heaney J, Pagliuzza A, Spyer M.J Frampton D, Rossi A.D, Palmas P, Giaquinto C, Conejo P.R, Foster C,  Rossi P, Klein N, Chomont N, Nastouli E, for the EPIICAL consortium

Presented at: Keystone symposia on molecular and cellular biology

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1

Dec, 2021

World AIDS Day 2021: How paediatric HIV has changed in the last 30 years

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It takes a community of people working together to achieve the results we are looking for: eradication HIV in children

 

The paediatric HIV pandemic has changed from when researchers first began investigating HIV in children to where we stand today.

The burden of perinatal infections, however, remains high. Perinatal infections occur when a pregnant person living with HIV passes HIV to her baby either during pregnancy, delivery or through breastfeeding. Despite unprecedented advances in the prevention of perinatal infections (including those occurring through breastfeeding) utilizing maternal ART and infant post- exposure preventative treatment, new infections continue. An estimated 1.8 million children under 15 years of age are living with HIV-1 globally, and 5 million survive to become adolescents and young adults with perinatal infection. In addition, around 150,000 children are born with HIV-1 annually, with about half of new infections occurring before and during birth and half through breastfeeding. The COVID-19 pandemic, through disruption of clinical care and its economic impact, increased these numbers in 2021 and beyond.

A multidisciplinary, multicultural approach to combat pediatric HIV-1 infection and discover immunotherapeutic strategies towards HIV remission, has been catalyzed by the EPIICAL consortium. The EPIICAL group of investigators and clinicians, through a number of virological and immunological studies conducted both in European HIV infected cohorts as well as in HIV positive African children, has gathered further evidence of efficacy of early therapy to reduce the amount of the virus within individuals and boost of specific immune responses. These studies will pave the way for further therapeutic strategies towards HIV remission using immunotherapeutic approaches.

From the clinical perspective, adherence in mother and child are strongly associated with achieving any therapeutic success. Barriers to the mother taking her therapy often mean that the child will also not be protected! But the mothers, if given the opportunity, do an amazing job at administering therapy to their children. It takes a community of people working together to achieve the results we are looking for and the work of social scientists plays a crucial role in identifying interventions that address non-adherence in mothers and children.

Holly Peay, senior Research Scientist at RTI International and EARTH social and behavioural study lead in EPIICAL, states that “Young children with HIV cannot control their own adherence. It is important to understand attitudes and barriers to adherence experienced by caregivers of children with HIV. That allows us to choose interventions that are targeted to the problems that caregivers experience and gives us hope that improving adherence in children will also improve adherence in their mothers and other HIV positive caregivers.”

The bottom line is, testing should never be delayed and early intervention can save the lives of both mother and the young child because when the mother is suppressed, the child is also likely to be suppressed.

Visit the EPIICAL website to learn more about the project.

23

Jul, 2021

CARMA study publishes article in Journal of International AIDS Society

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The CARMA team in the EPIICAL consortium have just published the article Early ART initiation during infancy preserves natural killer cells in young European adolescents living with HIV (CARMA cohort) in the Journal of International AIDS Society.

HIV infection causes pathological changes in the natural killer cell compartment, a type of white blood cell with enzymes that kill cells infected with a virus. Through antiretroviral therapy (ART), this compartment can be partially restored. The CARMA team looked into the characteristics and function of natural killer cells in children born with HIV and long-term viral control (five years) due to effective ART and whether the age at which ART was started had an impact on the viral reservoir.

Through this investigation, the team revealed that starting ART early in life, specifically during infancy, leads to the preservation of the NK compartment and is associated with a lower HIV-1 reservoir. This can continue on through adolescence if ART is adhered to as it leads to long-term viral control.

Visit the EPIICAL website to learn more about the CARMA study

 

Read the full article here

 

 

12

Mar, 2021

Sharing our understanding of the immune response of children living with HIV

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EPIICAL is proud to have presented four abstracts at the CROI conference this year, sharing updated information on viral decay and the immune response of children living with HIV who begin treatment early in life.

 

  • EFFECT OF HIV ON IMMUNE ACTIVATION AND EXHAUSTION IN CD4 AND CD8 T CELLS IN INFANTS Stefano Rinaldi, Vinh B. Dinh, Suresh Pallikkuth, Lesley D. Armas, Nadia Sitoe, Rajendra Pahwa, Nicola Cotugno, Paula Vaz, Paolo Palma, MariaGrazia Lain, Savita G. Pahwa
  • DYNAMICS OF INTACT PROVIRAL SEQUENCES IN EARLY TREATED HIV-1 CLADE C–INFECTED INFANTS Catherine K. Koofhethile, Stefano Rinaldi, Yelizaveta Rassadkina, Vinh B. Dinh, Ce Gao, Suresh Pallikkuth, Pilar Garcia-Broncano, Lesley D. Armas, Rajendra Pahwa, Nicola Cotugno, Maria Grazia Lain, Paolo Palma, Roger Shapiro, Savita G. Pahwa, Mathias Lichterfeld
  • VIRAL-RESERVOIR LANDSCAPE IN EARLY-TREATED VERTICALLY HIVINFECTED ADOLESCENTS Libera Sessa, Xiaodong Lian, Ce Gao, Nicola Cotugno, Alessandra Ruggiero, Xu G. Yu, Paolo Palma, Mathias Lichterfeld
  • FASTER INITIAL VIRAL DECAY IN FEMALE CHILDREN LIVING WITH HIV Sara Dominguez-Rodr.guez, Miquel Serna-Pascual, Caroline Foster, Paolo Palma, Eleni Nastouli, Anita De Rossi, Javier Seoane, Paolo Rossi, Carlo Giaquinto, Alfredo Tagarro, Pablo Rojo, for the EPIICAL Consortium

Follow this link to view the Abstract booklet

 

The CROI conference, which was held virtually from March 6-10, provided delegates with the opportunity to present new data on their HIV research and development studies. CROI is a long-standing conference that has provided a forum for scientists and investigators to present, discuss and critique research into human retroviruses and associated diseases. Over the years, the congress has facilitated the presentation of important discoveries and contributed to the acceleration in the understanding and progress in HIV/AIDS research.

The EPIICAL Consortium has successfully conducted studies on children living with HIV by setting up different well-characterized cohorts in Europe and Africa. The presented abstracts explored the factors that affect the immune response and the viral dynamics in children with a special focus on the early antiretroviral treatment. All these data are really informative and represent the basis to tailor immune therapeutic strategies in HIV infected children.

Thank you to all the authors for your invaluable contribution towards improving the understanding of HIV infection in children.

Learn more about EPIICAL here

Visit the EPIICAL website

21

Jul, 2020

The CARMA study: early infant antiretroviral therapy—Timing impacts on total HIV-1 DNA quantitation 12 years later

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Authors: Foster C, Domínguez-Rodríguez S, Tagarro A, et al. For the Early Treated Perinatally HIV Infected Individuals: Improving Children’s Actual Life (EPIICAL) Consortium

Published in: J Pediatr Infect Dis Soc. 2020 2020 Jul 17;piaa071

Background Strategies aimed at antiretroviral therapy (ART)–free remission will target individuals with a limited viral reser- voir. We investigated factors associated with low reservoir measured as total human immunodeficiency virus type 1 (HIV-1) DNA in peripheral blood mononuclear cells (PBMCs) in perinatal infection (PaHIV).

Methods Children from 7 European centers in the Early Treated Perinatally HIV Infected Individuals: Improving Children’s Actual Life (EPIICAL) consortium who commenced ART aged <2 years, and remained suppressed (viral load [VL] <50 copies/mL) for >5 years were included. Total HIV-1 DNA was measured by quantitative polymerase chain reaction per million PBMCs. Factors associated with total HIV-1 DNA were analyzed using generalized additive models. Age, VL at ART initiation, and baseline CD4% effects were tested including smoothing splines to test nonlinear association.

Results Forty PaHIV, 27 (67.5%) female 21 (52.5%) Black/Black African, had total HIV-1 DNA measured; median 12 (IQR, 7.3– 15.4) years after ART initiation. Eleven had total HIV-1 DNA <10 copies/106 PBMCs. HIV-1 DNA levels were positively associated with age and VL at ART initiation, baseline CD4%, and Western blot antibody score. Age at ART initiation presented a linear associ- ation (coefficient = 0.10 ± 0.001, P ≤ .001), the effect of VL (coefficient = 0.35 ± 0.1, P ≤ .001) noticeable >6 logs. The effect of CD4% (coefficient = 0.03 ± 0.01, P = .049) was not maintained >40%.

Conclusions In this PaHIV cohort, reduced total HIV-1 DNA levels were associated with younger age and lower VL at ART initiation. The impact of early-infant treatment on reservoir size persists after a decade of suppressive therapy.

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28

Feb, 2020

ushr: Understanding suppression of HIV in R

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Authors: Morris SE, Dziobek-Garrett L, Yates AJ and the EPIICAL consortium

Published in: BMC Bioinformatics 2020;21(1):52

Background HIV/AIDS is responsible for the deaths of one million people every year. Although mathematical modeling has provided many insights into the dynamics of HIV infection, there is still a lack of accessible tools for researchers unfamiliar with modeling techniques to apply them to their own clinical data.

19

Feb, 2020

New publications from EPIICAL Consortium

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Just published – data on T & B cell memory and T cell function in early-treated children in the Journal of Immunology and AIDS.
Antiretroviral treatment (if started at an early stage) is able to reduce the amount of HIV virus in a child’s body. EPIICAL is studying the characteristics of the immune response and the amount of HIV virus, in children with HIV who are treated at an early stage. This is to outline treatment strategies to help find a cure for HIV.

Congratulations to all the authors!

20

Nov, 2019

Universal Children’s Day

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Today, November 20th, is Universal Children’s Day. This year, we are celebrating in Cape Town, South Africa, where the EPIICAL 3rd General Assembly is being hosted. Universal Children’s Day is dedicated to the rights of the child, with one key aspect being the right for every child to access the highest standard of health. However, at the end of 2018, there were 37.9 million people living with HIV worldwide and, among them, 1.7 million are children aged less the 15 years.

The Early treated Perinatally HIV Infected Individuals (EPIICAL) is the world’s largest consortium dedicated to science of HIV remission, consisting of well-known scientists and clinicians working in HIV and pediatrics, from 26 institutions worldwide.

EPIICAL is strongly committed to fighting the HIV paediatric epidemic. Unique to the EPIICAL study are the cohorts of HIV-infected children who are treated early, and will be studied to develop strategies to develop treatment for HIV remission in HIV-infected children.
The knowledge gained from the consortium’s work has the potential to transform the lives of HIV-infected children worldwide, as well as potential applicability for the treatment of HIV in adults, particularly those who initiate early anti-retroviral therapy.

4

Oct, 2019

‘EARTH’ study – first patient enrolled in Mali

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We are delighted to report that the Centre Hospitalier Universitaire Gabriel Touré in Mali (in liaison with Anne-Genevieve Marcelin, France) has enrolled its first patient in the key EPIICAL study, ‘EARTH’. This marks a new chapter in the study, with the scope of the cohort widening to include participants not only from South Africa and Mozambique, but also from the west African site in Bamako.

EARTHCohort of Early Anti-Retroviral Treatment in HIV-perinatally infected Children – is a prospective multicentre, low-interventional study of HIV+ perinatally infected children on sustained suppressive antiretroviral therapy started before 3 months of age.

The study is firmly nested in the goals of the milestone EPIICAL project, with the primary aim being to engage in care and monitor clinical, virological and immunological features of early treated children in limited-resource settings. This is, ultimately, in order to identify potential participants in proof-of-concept trials directed towards a HIV cure.

We extend our thanks to Laboratory leader, Almoustapha Issiaka, and Clinical leader, Mariam Sylla, who are coordinating the important work being carried out by their team in Mali.

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