EPIICAL

21

Jul, 2020

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

Tags: ,

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.

Read

28

Feb, 2020

ushr: Understanding suppression of HIV in R

Tags: , ,

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.

Results Here we present ushr, a free and open-source R package that models the decline of HIV during antiretroviral treatment (ART) using a popular mathematical framework. ushr can be applied to longitudinal data of viral load measurements, and provides processing tools to prepare it for computational analysis. By mathematically fitting the data, important biological parameters can then be estimated, including the lifespans of short and long-lived infected cells, and the time to reach viral suppression below a defined detection threshold. The package also provides visualization and summary tools for fast assessment of model results.

Conclusions ushr enables researchers without a strong mathematical or computational background to model the dynamics of HIV using longitudinal clinical data. Increasing accessibility to such methods may facilitate quantitative analysis across a broader range of independent studies, so that greater insights on HIV infection and treatment dynamics may be gained.

19

Feb, 2020

New publications from EPIICAL Consortium

Tags: , ,

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

Tags: , ,

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

Tags: ,

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.

13

May, 2019

1st EPIICAL Newsletter

Tags: , , ,

With the EPIICAL project being a hive of activity over the last year, we have collected a selection of contributions, stories and articles to bring you the very first edition of the EPIICAL newsletter! The issue contains an update on the evolution and recent progress in the HIV pediatric research coordinated by the project. We get to know the clinicians that locally sustain HIV programs and services with reports of their experience in the EARTH (‘Early Anti-Retroviral Treatment in HIV-infected Children’) study. Moreover, we take a closer look at a team of young researchers in their day-to-day work. We extend our thanks to all involved who contributed with their views, knowledge and personal skills to highlight the spirit and mission of the EPIICAL consortium.

Read more here!

15

Mar, 2019

CROI 2019: Oral presentation by members of the EPIICAL team

Tags: , ,

The annual Conference on Retroviruses and Opportunistic Infections (CROI) was held on 4-7 March 2019, at the Washington State Convention Center in Seattle, Washington. CROI brings together top basic, translational, and clinical researchers from around the world to share the latest studies, important developments, and best research methods in the ongoing battle against HIV/AIDS and related infectious diseases.

At this year’s event, EPIICAL team member Sara Dominguez Rodriguez delivered the following oral presentation:

NEONATAL ART < 7 DAYS VS 7-28 DAYS REDUCED TIME TO SUPPRESSION

Alfredo Tagarro, Sara Dominguez Rodriguez, Thanyawee Puthanakit, Paolo Palma, Caroline Foster, Thidarat Jupimai, Nicola Cotugno, Jintanat Ananworanich, Santiago Jimenez de Ory, Paola Zangari, Maria Luisa Navarro, Paolo Rossi, Eleni Nastouli, Carlo Giaquinto, Pablo Rojo Conejo

This important study illustrated recent results that provide further evidence that supports the earliest antiretroviral therapy initiation in infants. Early antiretroviral therapy (ART) in children is associated with better clinical and virological outcome. The hypothesis explored is that HIV-perinatally infected neonates initiating ART within <7 days of life have a better long-term clinical and virological response than neonates treated ≥7 days and ≤28 days of life.

You can find the full webcast of the presentation here.

1

Mar, 2019

CROI: Members of the EPIICAL team to attend in Seattle

Tags: , , ,

Seattle is gearing up for the 2019 edition of CROI next week. Held at Washington State Convention Center on 4th-7th March, the Conference on Retroviruses and Opportunistic Infections is an important event in the Penta calendar, and in particular for the EPIICAL consortium, as it is an opportunity for members to discuss the latest developments pertaining to the project. Included on the agenda, EPIICAL project researchers will make an oral presentation illustrating recent results that provide further evidence that supports the earliest ART initiation in infants.

CROI is a global model of collaborative science and the premier international venue for bridging basic and clinical investigation to clinical practice in the field of HIV and related viruses. Established in 1993, the event provides a forum for basic scientists and clinical investigators to present, discuss, and critique their investigations into the epidemiology and biology of human retroviruses and associated diseases. It is the preeminent HIV research meeting in the world and attracts more than 4,000 HIV/AIDS research leaders internationally. The goal of the conference is to provide a forum for researchers to translate their laboratory and clinical findings into tangible progress against the HIV pandemic.

20

Nov, 2018

The EPIICAL 2nd General Assembly was a fabulous success!

Tags:

Held at the Hospital General Universitario Gregorio Marañón on 14th to 16th November 2018, the 2nd EPIICAL General Assembly welcomed around 50 scientists and healthcare professionals working together to establish new scientific efforts leading to HIV remission in children.

The 3-day meeting gave rise to highly fruitful discussion, at a time when the project has entered a very active phase, with new collaborations ready to start and a closer collaboration with the ViiV research network.

The Assembly acknowledged that EPIICAL is “a tough, large and world mixed project, made of people pulling together research in order to come up with a strategy which ultimately will produce new therapeutic strategies for curing HIV-infected children and new ways of using them”.

We extend a big thank you to Maria Angeles Muñoz-Fernandez, María Dolores García Alonso and José Luis Jimenez from Hospital General Universitario Gregorio Marañón for their warm hospitality and their untiring effort over the course of the event.

We also owe a special thanks to the ViiV HC team for being part of the EPIICAL family in these 3 days of intensive exchange and for their inspiring contributions to the discussion.

Looking forward to meeting you all in Cape Town next year!


 

Funded by an unrestricted industry grant, EPIICAL aims to implement a predictive platform for the early identification of novel therapeutic strategies for HIV infected children. This involves developing and applying a statistical and mathematical modelling to data derived from cohorts of early treated infants and children to identify virological, immunological and transcriptomic profiles associated with early control of HIV infection after ART initiation as well as viral control following ART interruption.

21

May, 2018

EARTH: first patient has been recruited!

Tags: , , ,

It is with great pleasure that we announce that the first patient in the EARTH study has been recruited. This encouraging news comes to us from the PHRU site in Soweto, South Africa. Now that all sites are open for recruitment, with some patients having already been screened, we are confident we will see more participants in the near future. earth-logoThis is the first of 150 children to be enrolled from one of 5 sites situated in South Africa and Mozambique.

The EARTH project, nested within the EPIICAL platform, is a prospective multicentre, low-interventional study of HIV+ perinatally infected children on sustained suppressive antiretroviral therapy (ART) commenced before 3 months of age.

We extend our thanks and congratulations to all the team at PHRU for their efforts and hard work in this study.