EPIICAL

18

Jun, 2019

Co-infection with HIV and HCV in 229 children and young adults living in Europe

 

Authors: Thorne C, Turkova A, Indolfi G, Venturini E, Giaquinto C

Published in: AIDS. 2017;31(1):127-135.

Objective To characterize children, adolescents and young adults infected with HIV/hepatitis C virus (HCV) vertically or before age of 18 years and living in Europe regarding mode of acquisition, HCV genotype, clinical status and treatment.

Design Retrospective, cross-sectional study using pooled data from 11 European paediatric HIV cohorts.

Methods Patients aged more than 18 months and less than 25 years, with HIV/HCV acquired vertically or in childhood, were included. Anonymized individual patient data were collected using a standard protocol and modified HIV Cohorts Data Exchange Protocol.

Results Of 229 patients included, 142 (62%) had vertically acquired infection. Median age at last follow-up was 16.2 years. Most children had HCV genotype 1 (101/184, 55%) or 3 (57/184, 31%). One-fifth (46/214) had a previous AIDS diagnosis (data missing on prior AIDS diagnoses for 15). At their last clinic visit, 70% (145/208) had no/mild immunosuppression (Centers for Disease Control and Prevention stage 1), and 131 of 179 on antiretroviral therapy had undetectable HIV RNA (assay thresholds varied from <20 to <150 copies/ml). Overall, 42% (86/204) had hepatomegaly in the previous year, and 55% (116/213) had alanine aminotransferase more than 40 IU/l at their last test. Of 97 patients with transient elastography, 12 had results more than 9 kPa; this was associated with duration of HCV infection (P = 0.033), but not with CD4 cell count, antiretroviral therapy use or sex in univariable analysis. Of 17 patients with liver biopsies, six had bridging fibrosis and one had cirrhosis. Twenty-five (11%) had been treated successfully for HCV.

Conclusion The high proportion of patients with progressive liver disease underscores the need for close monitoring and earlier and more effective HCV treatment.

28

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; 28. doi:10

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.

 

26

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: J Acquir Immune Defic Syndr. 2018;79(2):269-276

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.

 

 

22

Jan, 2018

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

 

Authors: P Zangari, P Palma, N Cotugno, et al.

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.

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14

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

Objective To investigate virological and immunological response to antiretroviral therapy (ART), and predictors of switching and interrupting treatment among infants starting ART across Europe.

Design Cohort study.

Methods Nine cohorts from 13 European countries contributed data on HIV-infected infants born 1996-2008 and starting ART before age 12 months. Logistic and linear regression, and competing risks methods were used to assess predictors of virological (viral load <400 copies/ml) and immunological (change in CD4 Z-score) response, switching to second-line ART and treatment interruptions with viral load less than 400 copies/ml.

Results A total of 437 infants were followed for median 5.9 (interquartile range 2.3-7.6) years after starting ART; 30% had an AIDS diagnosis prior to ART initiation. 53% had suppressed viral load <400 copies/ml at 12 months in 1996-1999, increasing to 77% in 2004-2008. Virological and immunological responses at 12 months varied by initial ART type (P < 0.001 and P = 0.03, respectively), with four-drug nonnucleoside reverse transcriptase inhibitor (NNRTI)-based regimens being superior [virological response <400 copies/ml adjusted odds ratio = 3.00, 95% confidence interval (CI) 1.24-7.23; mean increase in CD4 Z-score coefficient = 0.64, 95% CI 0.10-1.17] to both three-drug NNRTI-based (reference) and boosted protease inhibitor regimens which were similar. Rates of switching to second-line ART were lower among children starting four-drug NNRTI-based and boosted protease inhibitor-based regimens compared with three-drug NNRTI regimens (P = 0.03). Sixty five percent of infants remained on first-line ART without treatment interruption after 5 years.

Conclusion Effective and prolonged responses to first-line ART can now be achieved in infants starting early ART outside trial settings. Superior responses to four-drug NNRTI compared with boosted protease inhibitor or three-drug NNRTI regimens need further evaluation, as does treatment interruption following early ART.

 

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30

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 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 vivoproof-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.

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