Dec, 2019

PD-1+ CD4 T cells are associated with HIV reservoir size and impaired function of T follicular helper cells in children and young adults on long-term viral control


Authors: S. Rinaldi, V. Dinh, S. Pallikkuth, L. De Armas, R. Pahwa, N. Cotugno, E. Nastouli, C. Foster, P. Palma, S. Pahwa

Published in: Poster presented at 9th International Workshop on HIV Persistence during Therapy; December, 2019; Miami, FL

Background: Curative strategies for HIV will need to eliminate the replication competent latent reservoir. CD4 T cells expressing Immune Checkpoint molecules (ICP) have been shown to preferentially harbor latent, replication-competent HIV. T follicular helper (Tfh) cell subset of CD4 T cells are critical for B cell differentiation. Here a cohort of HIV vertically infected children and young adults under durable viral control (PHIV) were investigated for CD4 ICP, immune activation (IA) markers and function in relation to HIV reservoir size.

Methods: 40 PHIV (4-19yrs age) who started ART <2 years of life and had undetectable viremia (<50 HIV copies/ml) for the past 5 years, were enrolled in 7 European research centers. HIV-DNA copies per million peripheral blood mononuclear cells (PBMC) were measured by real-time PCR. Flow cytometry was used to investigate CD4 T cells for 1) co-expression of PD1 with IA (ICOS, CD38, Ki67 and HLA-DR) or ICP (TIGIT, LAG3, TIM3 and CTLA4) and 2) intracellular cytokine production (IL2, IFNg, TNFα, IL21) after stimulation with ENV peptides. Pearson correlations and 2 group comparisons were performed using the Mann-Whitney T Test. P value<0.05 was considered significant.

Results: Total PD1+ CD4 T cells positively correlated with HIV-DNA (r=0.46) as did CD4 T cells co-expressing PD1 with other ICP or IA (table 1 below). We then divided our cohort based on HIV-DNA distribution into those with high (4th quartile) and low (1st quartile) HIV-DNA. We found that PD1+ CD4 T cells co-expressing IA or ICP were higher in participants with high HIV-DNA (table 1). PD1+ CD4 T cells also showed negative correlation with ENV antigen activated Tfh expressing CD40L (r=-0.41, p<0.05) with selective induction of IL2 (r=0.47, p<0.05), a cytokine that is inhibitory for Tfh.

Conclusions: This study suggests that PD-1 expression on CD4 T cells is associated with dysfunctional T:B cell interaction in response to HIV antigens, and supports the association of PD1 expression on CD4 T cells with size of viral reservoirs in vertically HIV infected children and young adults under long-term viral control.


Dec, 2019

Standardising neonatal and pediatric anitibiotic clinical trial design and conduct: the PENTA-ID network review

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Authors: Folgori L, Lutsar I, Standing JF, et al.

Published in: BMJ Open. 2019; 9:e032592

Abstract: Antimicrobial development for children remains challenging due to multiple barriers to conducting randomised clinical trials (CTs). There is currently considerable heterogeneity in the design and conduct of paediatric antibiotic studies, hampering comparison and meta-analytic approaches. The board of the European networks for paediatric research at the European Medicines Agency (EMA), in collaboration with the Paediatric European Network for Treatments of AIDS-Infectious Diseases network (www.penta-id.org), recently developed a Working Group on paediatric antibiotic CT design, involving academic, regulatory and industry representatives. The evidence base for any specific criteria for the design and conduct of efficacy and safety antibiotic trials for children is very limited and will evolve over time as further studies are conducted. The suggestions being put forward here are based on the adult EMA guidance, adapted for neonates and children. In particular, this document provides suggested guidance on the general principles of harmonisation between regulatory and strategic trials, including (1) standardised key inclusion/exclusion criteria and widely applicable outcome measures for specific clinical infectious syndromes (CIS) to be used in CTs on efficacy of antibiotic in children; (2) key components of safety that should be reported in paediatric antibiotic CTs; (3) standardised sample sizes for safety studies. Summarising views from a range of key stakeholders, specific criteria for the design and conduct of efficacy and safety antibiotic trials in specific CIS for children have been suggested. The recommended criteria are intended to be applicable to both regulatory and clinical investigator-led strategic trials and could be the basis for harmonisation in the design and conduct of CTs on antibiotics in children. The next step is further discussion internationally with investigators, paediatric CTs networks and regulators.


Dec, 2019

Season’s Greetings from Penta!


Christmas is a time of the year that we usually spend with those we love: it reminds us of the importance of relationships.

Sharing experiences and communicating on with others are essential in life, and one of the core beliefs of Penta is sharing. At Penta, we are always eager to build new collaborations and increase and encourage the exchange of knowledge and ideas. Our ability to innovate and implement change comes from our strong collaborations. This year we have welcomed new partnerships, which have enabled us to explore new opportunities in transforming the prevention and treatment of infections in children. Among them, we would like to greet our Malian friends, who have recently joined EPIICAL consortium. In Mali only 21% of HIV infected children are receiving antiretroviral treatment, and through EPIICAL we will help increase the number of children diagnosed and treated in that country. This is very important for us here at Penta, as it is a step towards the achievement of our vision of a world where all children with infection get the treatment they need.

We’d like to wish all of you a very Merry Christmas, and thank you all for your precious support and collaboration. Let’s continue working together to ensure that no child is left behind.



Dec, 2019

Data from ODYSSEY are used by ViiV Healthcare to file FDA and EMA submissions for the first-ever dispersible formulation of dolutegravir for children living with HIV


Using data from the ongoing P1093 and the ODYSSEY (PENTA20) study, ViiV Healthcare has filed submissions to the FDA and EMA for the first-ever dispersible formulation of dolutegravir (DTG) for children living with HIV.

If approved, this new formulation of dolutegravir will be the first integrase inhibitor available as a dispersible tablet for children living with HIV, closing the gap between treatment options available for adults and children.

Data to support the submissions has been generated from ViiV Healthcare’s collaborations with the U.S. National Institutes of Health (NIH) and the International Maternal Pediatric Adolescent AIDS Clinical Trials Network (IMPAACT) for P1093 and Penta for ODYSSEY.

A full press release from ViiV can be found here.

ODYSSEY is a pragmatic strategy trial evaluating the efficacy and safety of once daily dolutegravir-based antiretroviral therapy compared with standard of care in children and adolescents starting first- or second-line antiretroviral therapy in resource-limited and well-resourced settings.

To know more about our study, visit the ODYSSEY website.


Dec, 2019

Role of Magnetic Resonance Imaging and cranial ultrasonography in congenital Cytomegalovirus infection


Authors: Blazquez-Gamero D, Soriano-Ramos M, Martinez de Aragon A, et al.

Published in: Pediatr Infect Dis J. 2019;38(11):1131-1137


Dec, 2019

Human Rights Day

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Today we celebrate Human’s Right Day: this year’s theme is “Youth Standing Up for Human Rights”.
School HIV-prevention campaigns in Africa are often designed to frighten children. However, we believe this should be done differently. By providing children with information about HIV we can help prevent fear and ensure children are educated.

Peer-support groups play an important role in providing children and adolescents with information they need about HIV.

Watch the full video by Picturing Health here.

#StandUp4HumanRights #HumanRightsDay


Dec, 2019

Picturing Health launches new video on adolescents with HIV

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Picturing Health has created the first video in a three part series of adolescent films about growing up with HIV. This series of short films tackles the issue of dealing with disclosure and the impact a child being told they are HIV positive.

Check out the video here: https://www.picturinghealth.org/finding-out/

There are also an additional 13 films from Picturing Health covering some of the main areas of paediatric HIV care, including early infant diagnosis, treatment and monitoring of exposed babies, initiation of antiretroviral therapy, side effects to antiretroviral drugs, opportunistic infections and investigating treatment failure.

These films are an excellent educational tool, and have been used as part of the Penta Tr@inforPedHIV courses.

In each film, the history of the child with HIV is presented, followed by images of examinations carried out and results of tests ordered. The films pose questions about diagnosis, treatment and management.

Viewers can find the answers to these questions posed in the films in the accompanying notes, which can be updated by users to accommodate changes in guidelines and treatment, or adapted to different settings. Notes covering each case can be downloaded from the individual film pages.

All resources produced by the charity are open access and can be freely accessed and disseminated.

Why don’t you take a look for yourself?


These videos have been produced through a collaboration between Picturing Health and Penta.


Dec, 2019

World AIDS Day 2019: Communities make the difference

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The theme of this year’s World AIDS Day, which we commemorate today, is “Communities make the difference“. Today we highlight the role of communities in ensuring that AIDS remains at the top of the political agenda. Therefore, continuing to respect human rights and enable decision-makers and implementers to be held accountable.

At Penta, we strongly believe in fighting paediatric AIDS. First established in 1991 as a collaboration between paediatric HIV centers in Europe, nowadays the Penta Network spans over 31 countries, and hosts  a community of investigators, healthcare workers, clinicians and patients. We keep people at the centre of all we do and ensure that no one is left behind.

Find out WHY we do what we do in this video.  #WorldAIDSDay #pentachildhealthresearch



Nov, 2019

Modulated Zika virus NS1 conjugate offers advantages for accurate detection of Zika virus specific antibody in double antigen binding and Ig capture enzyme immunoassays


Authors: Tedder RS, Dicks S, Ijaz S, et al.

Published in: PLoS One. 2019;14(8):e0215708

Abstract: The accurate diagnosis and seroprevalence investigations of Zika virus (ZKV) infections remain complex due to cross reactivity with other flaviviruses. Two assay formats, both using labelled Zika virus NS1 antigen as a revealing agent (a double antigen binding assay, DABA, and an immunoglobulin Ig capture assay, G capture) were initially developed and compared with the indirect EuroimmunZ assay for the detection of anti-Zika antibody. Of 147 pre-Zika period serum samples, 39 (27%) were reactive in the EuroimmunZ or the DABA assays, 28 sera concordantly so. Such false reactivity was influenced by the serotype of Dengue virus (DV) to which individuals had been exposed to. Thus, of sera from patients undergoing secondary Dengue virus infection of known serotype, 91%, 45% and 28% of Dengue virus serotype 2, 3 and 4 respectively were reactive in one or more of the three assays. A novel method of quenching false sero-reactivity was therefore developed for the DABA and G capture assays. Initial addition of a single homologous Dengue virus serotype 3 NS1Ag quench significantly ablated false reactivities in the pre-Zika period sera. An equipotent quadrivalent quench comprising homologous Dengue virus serotypes 1 to 4 NS1Ag was shown to be optimum yet retained sensitivity for the detection of specific anti-Zika antibody. Comparing DABA and G capture assays using quenched and unquenched conjugates in comparison with EuroimmunZ early in the course of PCR-confirmed infection indicated that a significant component of the apparent early anti-ZIKA antibody response is likely to be due to a Zika virus-driven anamnestic anti-Dengue virus response. The increased specificity provided by homologous antigen quenching is likely to provide a significant improvement in sero-diagnostics and to be of clinical value.




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.


We would like to update you on our recent activities