Aug, 2018

Human Immunodeficiency Virus (HIV) – Antibody Repertoire Estimates Reservoir Size and Time of Antiretroviral Therapy Initiation in Virally Suppressed Perinatally HIV-Infected Children


Authors: Rocca S, Zangari P, Cotugno N, et al.

Published in: J Pediatric Infect Dis Soc. 2018


Background. Assays to estimate human immunodeficiency virus (HIV) reservoir size require large amounts of blood, which represents a drawback especially in pediatric settings. We investigated whether HIV-antibody repertoire could estimate the viral reservoir size. Moreover, we assessed the magnitude of HIV-antibody response as a predictor of time of antiretroviral therapy (ART) initiation.

Methods. Human immunodeficiency virus-antibody responses to 10 different viral proteins were evaluated by HIV Western blot (WB) kit and a WB score was assigned to each patient. Patients were classified in 2 subgroups based on the timing of ART initiation (early treated [ET], 0–24 weeks and late treated [LT], >24 weeks). Human immunodeficiency virus-deoxyribonucleic acid (DNA) was quantified using real-time quantitative polymerase chain reaction on total peripheral blood mononuclear cells. Logistic regression and principal component analysis were built on these data to test the ability of WB score to predict the expected value of HIV-DNA and the timing of ART initiation.

Results. Sixty-nine perinatally HIV-infected children were evaluated. Reduced HIV-specific antibody responses and lower size of HIV-DNA were observed in ET compared with LT patients (P < .001 and P = .02, respectively). We found that WB score correlates with HIV-DNA (P = .032) and timing of ART initiation (P < .001). Based on the logistic regression analysis, we found that WB score can predict the HIV-DNA size and the timing of ART initiation with an Akaike information criterion of −118.13 and −151.51, respectively.

Conclusions. Western blot score can estimate HIV-DNA size and timing of ART initiation in long-term virally suppressed children. This rapid, inexpensive, and easily reproducible tool can provide useful information to identify potential candidates for HIV remission studies.



Jun, 2018

Early and highly suppressive ART are main factors associated with low viral reservoir in European perinatally HIV infected children


Authors: A Tagarro, M Chan, P Zangari, et al. on behalf of the EPIICAL Consortium

Published in: JAIDS Journal of Acquired Immune Deficiency Syndromes. June 26, 2018


Background. Future strategies aiming to achieve HIV-1 remission are likely to target individuals with small reservoir size.

Setting. We retrospectively investigated factors associated with HIV-1 DNA levels in European, perinatally HIV-infected children starting ART <6 months of age.

Methods: Total HIV-1 DNA was measured from 51 long-term suppressed children 6.3 years (median) after initial viral suppression. Factors associated with log10 total HIV-1 DNA were analyzed using linear regression.

Results. At ART initiation, children were aged median [IQR] 2.3 [1.2,4.1] months, CD4% 37 [24,45] %, CD8% 28 [18,36] %, log10 plasma viral load (VL) 5.4 [4.4,5.9] copies/ml. Time to viral suppression was 7.98 [4.6,19.3] months. Following suppression, 13 (25%) children had suboptimal response [≥2 consecutive VL50-400 followed by VL<50] and/or experienced periods of virological failure [≥2 consecutive VL≥400 followed by VL<50]. Median total HIV-1 DNA was 43 [6,195] copies/106 PBMC.

Younger age at therapy initiation was associated with lower total HIV-1 DNA (adjusted coefficient [AC] 0.12 per month older, p=0.0091), with a month increase in age at ART start being associated with a 13% increase in HIV DNA. Similarly, a higher proportion of time spent virally suppressed (AC 0.10 per 10% higher, p=0.0022) and absence of viral failure/suboptimal response (AC 0.34 for those with fail/ suboptimal response, p=0.0483) were associated with lower total HIV-1 DNA.

Conclusion. Early ART initiation and a higher proportion of time suppressed are linked with lower total HIV-1 DNA. Early ART start and improving adherence in perinatally HIV-1 infected children minimize the size of viral reservoir.

This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial License 4.0 (CCBY-NC), where it is permissible to download, share, remix, transform, and buildup the work provided it is properly cited. The work cannot be used commercially without permission from the journal.

DOI: 10.1097/QAI.0000000000001789

The article is available here.



Jan, 2018

Report from the First EPIICAL General Assembly meeting, 9–11 November 2017, Rome, Italy


Authors: P Zangari, P Palma, N Cotugno, P Rojo, A Tagarro, I Pepponi, A De Rossi, L Kuhn, S Pahwa, M Cameron, E Nastouli, S Watters, AG Marceline, LE McCoy, D Persaud, A Violari, M Chan, AG Babiker, C Foster, J Ananworanich, C Giaquinto, P Rossi

Published in: Journal of Virus Eradication 2018; 4: 51–54

Abstract: The first EPIICAL General Assembly meeting was held in an atmosphere of growing optimism. Many novel and exciting proposals for HIV research studies were discussed and are described above. The consortium aims to maintain this integrated developmental research on NDMTs, from predictive platforms to proof-of-concept studies, through the excellent collaborative effort made during the first 18 months of EPIICAL, some of which is described in this report. The emphasis on an innovative research platform is unique and may lead to optimisation of the management of perinatally HIV-infected children. Collectively, the updates and the discussions from the General Assembly attest to the benefit of nurturing an international collaborative effort on paediatric HIV research and confirm that EPIICAL is successfully on track.



Jul, 2015

Early antiretroviral therapy in children perinatally infected with HIV: a unique opportunity to implement immunotherapeutic approaches to prolong viral remission


Authors: Klein N, Palma P, Luzuriaga K, et al.

Published in: Lancet Infect Dis. 2015;15(9):1108-1114.

Abstract: From the use of antiretroviral therapy to prevent mother-to-child transmission to the possibility of HIV cure hinted at by the Mississippi baby experience, paediatric HIV infection has been pivotal to our understanding of HIV pathogenesis and management. Daily medication and indefinite antiretroviral therapy is recommended for children infected with HIV. Maintenance of life-long adherence is difficult and the incidence of triple-class virological failure after initiation of antiretroviral therapy increases with time. This challenge shows the urgent need to define novel strategies to provide long-term viral suppression that will allow safe interruption of antiretroviral therapy without viral rebound and any associated complications. HIV-infected babies treated within a few days of birth have a unique combination of a very small pool of integrated viruses, a very high proportion of relatively HIV resistant naive T cells, and an unparalleled capacity to regenerate an immune repertoire. These features make this group the optimum model population to investigate the potential efficacy of immune-based therapies. If successful, these investigations could change the way we manage HIV infection.


Jun, 2015

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


Authors: Palma P, Foster C, Rojo P, et al.

Published in: J Virus Erad. 2015;1(3):134-139.

Abstract: The European Paediatric Mycology Network (EPMyN) was launched in 2014 to create a European platform for research and education in the field of paediatric mycology. The EPMyN aims to address the lack of paediatric specific evidence and knowledge needed to (1) improve the management and outcome of invasive fungal infections in children and neonates and to (2) enhance and develop paediatric antifungal stewardship programmes.