HIV | Eppicc

Authors: Edgar K, The Epidemiology of Pregnancy and Paediatric Infections International Cohort Collaboration (EPPICC) study group

Published in: Open Forum Infectious Diseases

Authors: Chappell E, The European Pregnancy and Paediatric Infections Cohort Collaboration (EPPICC) Study Group

Published in: International Journal of Antimicrobial Agents

Authors: The European Pregnancy and Paediatric Infections Cohort Collaboration (EPPICC) Study Group

Published in: HIV Medicine

Authors: O’Rourke J, Chappell E, Collins IJ, Crichton S, Ene L, Le Coeur S, Le Prevost M, Marques L, Naver L, Noguera-Julian A, Pluta M, Prime K, Ramos JT, Spoulou V, van Aerde K, Trickey A, Judd A, on behalf of the Epidemiology of Pregnancy and Paediatric Infections International Cohort Collaboration (EPPICC).

Presented at: International Workshop on Pediatrics and HIV

Authors: Edgar K, Scott K, Castro H, O’Rourke J, Ene L, Galli L, Goetghebuer T, Henegar C, Hoffmann TU, Koenigs C, Marczyńska M, Naver L, Noguera-Julian A, Paioni P, Puthanakit T, Ramos Amador JT, Spoulou V, Tantawarak N, Vannappagari V, Volokha A, Turkova A, Judd A, Collins IJ, Crichton S, on behalf of the Epidemiology of Pregnancy and Paediatric Infections International Cohort Collaboration (EPPICC)

Presented at: International Workshop on Pedatrics and HIV

Authors: Scott K, O’Rourke J, Jackson C, Ene L, Galli L, Goetghebuer T, Henegar C, Königs C, Marczyńska M, Naver L, Noguera-Julian A, Paioni P, Ramos JT, Smith B, Songtaweesin WN, Spoulou V, Tantawarak N, Turkova A, Vannappagari V, Volokha A, Bamford A, Castro H, Chappell E, Dalla Valle G, Foster C, Guillén Martín S, Prieto Tato LM, Puthanakit T, Sherstiuk H, Shkurka I, Soeria-Atmadja S, Judd A, Crichton S, Collins IJ

Published in: Clinical Infectious Diseases

Authors: European Pregnancy and Paediatric Infections Cohort Collaboration (EPPICC) SARS-CoV-2 Antibody Study Group

Published in: Epidemiology and Infections

Authors: Sconza R, Fernandes G, Bailey H, Peters H, Prieto Tato LM, Illán Ramos M, Aebi-Popp K, Kahlert C, Gamell AM, Frick A, Ene L, Samarina A, Thorne C; European Pregnancy and Paediatric Infections Cohort Collaboration (EPPICC)

Published in: Journal of Acquired Immune Deficiency Syndrome

Authors: Scott K, Castro H, O’Rourke J, Edgar K, Ene L, Galli L, Goetghebuer T, Henegar C, Hoffmann UT, Königs C, Marczyńska M, Naver L, Noguera-Julian A, Paioni P, Puthanakit T, Ramos Amador JT, Spoulou V, Tantawarak N, Vannappagari V, Volokha A, Turkova A, Judd A, Collins IJ, Crichton S, on behalf of the Epidemiology of Pregnancy and Paediatric Infections International Cohort Collaboration (EPPICC)

Presented at: International Workshop on HIV and Pediatrics

Authors: Fernandes G, Chappell E, Sconza R, Bailey H, Dalla Valle G, Aebi-Popp K, Ene L, Floridia M, Gamell A, Illán Ramos M, Peters H, Samarina A, Bamford A, Thorne C; for the EPPICC Pregnancy Study Group.

Presented at: International workshop on HIV and pediatrics

Authors: Fernandes G, Chappell E, Sconza R, Bailey H, Valle DG, Aebi-Popp K, Ene L, Floridia M, Gamell A, Ramos IM , Peters H, Samarina A, Bamford A, Thorne C  for the EPPICC Pregnancy Study Group.

Presented at: International workshop on HIV and pediatrics

Authors: Scott K, O’Rourke J, Jackson C, Ene L, Galli L, Goetghebuer T, Henegar C, Königs C, Marczyńska M, Naver L, Noguera-Julian A, Paioni P, Ramos JT, Smith B, Songtaweesin WN, Spoulou V, Tantawarak N, Turkova A, Vannappagari V, et al

Published in: Clinical Infectious Diseases

Authors: Jackson C, Crichton S, Judd A, Bamford A, Goulder P, Klein N, Marques L, Paioni P, Riordan A, Spoulou V, Vieira VA, Ansone S, Chiappini E, Le Coeur S, Ene L, Galli L, Giaquinto C, Goetghebuer T, Fortuny C, Kanjanavanit S, Marczynska M, et al

Published in: AIDS

Authors: Sconza R, Fernandes G, Bailey H, Aebi-Popp K, Ene L, Floridia M, Gamell MA, Ramos IM, Peters H, Samarina A, Ragone L, Vannappagari V,Thorne C for Dolomite-EPPICC Study Group

Presented at: Glasgow HIV

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Authors: Scott K, Crichton S, O’Rourke J, Chappell E, Ene L, Galli L, Goetghebuer T, Henegar C, Hoffmann T,  Königs C, Magdalena Marczyńska M,  Naver L,  Noguera-Julian A,  Paioni P, Ramos TJ, Songtaweesin W, Spoulou V, ​Tantawarak N, Vannappagari V, Volokha A, Turkova A, Judd A, Collins JI

Presented at: AIDS 2024 and International workshop on HIV & pediatrics 2024

Authors: Crichton S, Edgar K, Scott K, Chappell E, Álvarez B, Ene L, Galli L, Goetghebuer T, Henegar C, Hoffmann UT, Kahlert C, Königs C, Marczyńska M, Naver L, Sainz A, Songtaweesin N W, Spoulou V, Tantawarak N, Vannappagari V, Volokha A, Turkova A, Judd A, Collins IJ on behalf of the European Pregnancy and Paediatric Infections Cohort Collaboration (EPPICC)

Presented at: AIDS 2024 and International workshop on HIV and pediatrics 2024

Authors: Scott K, O’Rourke J, Crichton S, Chappell E, Ene L, Galli L, Goetghebuer T, Henegar C, Hoffmann UT, Königs C, Marczyńska M, Naver L, Noguera-Julian A, Paioni P, Ramos TJ, Songtaweesin NW, Spoulou V, Tantawarak N, Vannappagari V, Volokha A, Turkova A, Judd A, Collins IJ on behalf of the European Pregnancy and Paediatric Infections Cohort Collaboration (EPPICC)

Presented at: International workshop on HIV and pediatrics 2024

Authors: Scott K, Crichton S, Jackson C, Ene L, Galli L, Goetghebuer T, Henegar C, Königs C, Marczyńska M, Naver L, Noguera-Julian A, Paioni P, Puthanakit T, Ramos TJ, Smith B, Spoulou V, Tantawarak N, Vannappagari V, Volokha A, Turkova A, Judd A, Collins IJ On behalf of the European Pregnancy and Paediatric Infections Cohort Collaboration (EPPICC)

Presented at: International workshop HIV and pediatrics 2024

Authors: Sconza R, Fernandes G, Aebi-Popp K, Ene L, Frick A, Gamell A, Ramos IM, Kahlert C, Peters H, Tato PML, Samarina A, Giaquinto C, Thorne C for the EPPICC Pregnancy Study Group

Presented at: CROI 2024

Authors: Thorne C, Aebi-Popp K, Ene L, Floridia M, Gamell A, Illan M, Peters H, Samarina A, Fernandes G, Sconza R, Ragone L, Giaquinto C, Vannappagari V

Presented at: EACS 2023

Authors: Chappell E, Bamford A, Sanchez AB, Goetghebuer T, Marques L, Navér L, Noguera-Julian A, Talarek E, Plotnikova Y, Samarina A, Ene L, Spoulou V, Collins IJ, Navarro ML, Plynsky AA, Chapygina Y, Fertikh E, Soeria-Atmadja S, Doerholt K, Welch S, Crichton S, Jackson C, Judd A, Scott K

Published in: AIDS

Authors: Jackson C, Crichton S, Bamford A, Berzosa A, Gilmour K, Goetghebuer T,  Johnson SM, Judd A, Noguera-Julian A, Le Prevost M, Spoulou V, Sturgeon K,  VolokhamA, Zar HJ, Collins IJ. On behalf of the European Pregnancy and Paediatric Infections Cohort Collaboration (EPPICC)

Presented at: CROI 2023

Authors: European Pregnancy And Paediatric Infections Cohort Collaboration Eppicc, Lyons A, Thompson L, Chappell E, Ene L, Galli L, Goetghebuer T, Jourdain G, Noguera-Julian A, Kahlert CR, Königs C, Kosalaraksa P, Lumbiganon P, Marczyńska M, Marques L, Navarro M, Naver L, Okhonskaia L, Prata F, Puthanakit T, Ramos JT, Samarina A, Thorne C, Voronin E, Turkova A, Giaquinto C, Judd A, Collins IJ

Published in: Sage Journals

Authors: Chappell E, Bamford A, Berzosa Sanchez A, Goetghebuer T, Marques L, Naver L, NogueraJulian A, Talarek E, Plotnikova Y, Samarina A, Ene L, Spolou V, Collins I

Presented at: International Workshop on HIV & Pediatrics 2022

Authors: C Thorne, K Aebi-Popp, L Ene, M Floridia, AM Gamell, M Illan, H Peters, A Samarina, L Ragone, C Giaquinto, V Vannappagari

Presented at: CROI 2022

Author: Anna Turkova, Evgeny Voronin, Yulia Plotnikova, Anna Samarina, Edith Milanzi, Vladimir Rozenberg, Liubov Okhonskaia, Inga Latysheva, Aleksey Plynsky, Elena Fertikh, Siobhan Crichton, Charlotte Jackson, Ali Judd, Intira J Collins, on behalf of the European Pregnancy and Paediatric Infections Cohort Collaboration (EPPICC)

Published in: 12th International Workshop on HIV Pediatrics

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Authors: Crichton S, Jesson J, Aké-Assi MH, Belfrage E, Davies MA, Pinto J, Teasdale C, Van Lam N, Vreeman R, Wanless S, Williams P, Yotebieng M, Leroy V, Goodall R on behalf of the CIPHER Global Cohort Collaboration

Published in: 27th Conference on Retroviruses and Opportunistic Infections, March 8th –11th, 2020 – Boston.

Authors: Crichton S , Collins  IJ, Turkova A, Ene L, Galli L, Marczynska M, Navarro M, Naver L, Noguera-Julian A, Plotnikova Y, Scherpbier H, Volokha A, Voronin E, Judd A; on behalf of the European Pregnancy and Paediatric Infections Cohort Collaboration (EPPICC)

Published in: 27th Conference on Retroviruses and Opportunistic Infections, March 8th –11th, 2020 – Boston.

Abstract

Background: The World Health Organization (WHO) recommends abacavir as the preferred/alternative backbone for 1st line regimens in children with HIV from age 28 days. There are limited data available on safety and tolerability of abacavir in young infants aged <3 months.

Methods: We describe infant and regimen characteristics at the start of abacavir (including drug combinations and dosing) and outcomes up to 12 months after first use of abacavir. Outcomes include:

• drug discontinuations (defined as interruption of abacavir for >30 days),
• clinical adverse events (AE, reported from start of abacavir, and up to 30 days after discontinuation of abacavir) and
• viral load at 6 and 12 (±3) months after start of abacavir

Conclusions: Across children initiating abacavir in early life in Europe, it was safe and well tolerated, and discontinuations for safety concerns were rare. • Viral suppression was below the UN-AIDS 90% target which may reflect challenges of treatment in infancy.

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Authors: Thorne C, Rasi V, Aebi-Popp K, Ene L, Floridia M, Mendoza-Palomar N, Prieto L, Ragone L, Sconza R, CGiaquinto C, Vannappagari V; for the Dolomite-EPPICC study group

Published in: Oral presentation at 27th Conference on Retroviruses and Opportunistic Infections, March 8th –11th, 2020 – Boston.

Abstract

BACKGROUND • In 2018, the Tsepamo Study, Botswana reported significant increased risk of NTD in women conceiving on DTG (0.94%) 1 leading to a safety alert • Updated analysis of NTD prevalence (08/2014 – 03/2019)2 • 5 NTDs/1,683 deliveries in women on DTG at conception (0.30%, 95% CI 0.13-0.69 vs 0.10%, 95% CI 0.06-0.17 for non-DTG ART at conception • The Antiretroviral Pregnancy Registry recently reported 1 NTD in 312 periconception DTG exposures (0.3%) 3 • The Dolomite Study was set up in 2017 to address use & safety of DTG in pregnancy and exposed infants in Europe and Canada; conducted within the NEAT-ID network and EPPICC (the European Pregnancy and Paediatric Infections Cohort Collaboration)

Aim: To assess pregnancy and neonatal outcomes following DTG use during pregnancy in real-world European settings • Objectives were to describe: • characteristics of pregnant women receiving DTG-based regimens • frequency of adverse pregnancy and birth outcomes, by earliest timing of DTG exposure

Method: Dolomite-EPPICC involves pooled analyses of prospectively collected individual patient data on DTG-exposed pregnancies from participating studies • Data specification based on a modified HIV Data Exchange Protocol (www.hicdep.org) • Data merger included • All pregnancies with any prenatal DTG exposure • With birth outcomes reported by Feb 2019 • Periconception DTG exposure was defined as initial exposure at ≤6 weeks of estimated gestational age (EGA)

Results: 453 pregnancies in 428 women included (Figure) • Pregnancies reported from six countries • 347 (76.6%) UK and Ireland, 45 (9.9%) Spain, 29 (6.4%) Switzerland, 29 (6.4%) Italy, 3 (0.7%) Romania

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Authors: Jackson C, Bamford A, Crichton S, Goodall R,Goulder P, Klein N, Marques L, Paioni P, Riordan A, Spoulou V, Vieira VA, Collins IJ. On behalf of The European Pregnancy and Paediatric Infections Cohort Collaboration (EPPICC) study group

Published in:  27th Conference on Retroviruses and Opportunistic Infections, March 8th –11th, 2020 – Boston.

Authors: European Pregnancy and Paediatric HIV Cohort Collaboration (EPPICC) study group in EuroCoord

Published in: HIV Med. 2019;20(5):291-307

Objectives Combination neonatal prophylaxis (CNP) is recommended in high‐risk situations for the prevention of mother‐to‐child HIV transmission, although data on its safety are limited. The aim of the study was to identify whether neonatal prophylaxis (NP) type is associated with the risk of severe anaemia or neutropaenia.

Methods An individual patient data meta‐analysis was conducted within six European cohorts, in infants at high risk for acquiring HIV infection. Adjusted logistic regression models were used to assess the risk of National Institute of Allergy and Infectious Diseases, Division of AIDS (DAIDS) grade 3–4 anaemia/neutropaenia at ages 0–6 months. Mixture models of haemoglobin (Hb) level and log₁₀‐transformed neutrophil count (NC) were used to explore associations with NP type at ages 0–18 months.

Results Of 1836 infants, 25% were preterm, 1149 (63%) had antenatal combination antiretroviral therapy (cART) exposure and 395 (22%) received NP (125 received CNP with three drugs). Overall, 117 (6.7%) infants had grade 3–4 anaemia at age 0–6 months and 140 (9.1%) had grade 3–4 neutropaenia. The presence of grade 3–4 anaemia or neutropaenia was not associated with NP type [adjusted odds ratio (aOR) 1.04 for one‐drug NP and 1.60 for three‐drug NP versus two‐drug NP (P = 0.879 and P = 0.277, respectively) for anaemia; aOR 1.33 for one‐drug NP and 1.98 for three‐drug NP versus two‐drug NP (P =0.330 and P =0.113, respectively) for neutropaenia], but was associated with preterm delivery. Overall, 7746 Hb and NC results were available for 1836 infants up to age 18 months; no significant differences in predicted Hb level or NC were apparent by NP type.

Conclusions A small proportion of infants experienced grade 3–4 haematological adverse events; risk of anaemia or netropenia was not associated with type of NP.

Authors: Collins IJ; European Pregnancy and Paediatric HIV Cohort Collaboration (EPPICC) study group in EuroCoord

Published in: Clin Infect Dis. 2019; 28. pii: ciz253. doi: 10.1093/cid/ciz253. [Epub ahead of print]

Background In HIV-positive adults, low CD4 cell counts despite fully suppressed HIV-1 RNA on antiretroviral therapy (ART) have been associated with increased risk of morbidity and mortality. We assessed the prevalence and outcomes of poor immune response (PIR) in children on suppressive ART.

Methods Sixteen cohorts from the European Pregnancy and Paediatric HIV Cohort Collaboration (EPPICC) contributed data. Children aged<18 years at ART initiation, with sustained viral suppression (VS) (≤400copies/mL) for ≥1 year were included. The prevalence of PIR (defined as WHO advanced/severe immunosuppression for age: CD4%<30% in children aged<12 months, CD4%<25% in 12-35 months, CD4%<20% in 36-59 months; CD4%<15%/CD4<350 cells/mm3 in ≥5-years) at 1 year of VS was described. Factors associated with PIR were assessed using logistic regression. Rates of AIDS or death on suppressive ART were calculated by PIR status.

Results Of 2318 children included, median age was 6.4 [IQR, 2.1, 10.4] years and 68% had advanced/severe immunosuppression at ART initiation. At 1 year of VS, 12% had PIR. In multivariable analysis, PIR was associated with older age and worse immunological stage at ART start, hepatitis-B coinfection and residing in Thailand (all p≤0.03). Rates of AIDS/death (95% CI) per 100,000 person-years were 1052 (547, 2022) among PIR versus 261 (166, 409) among immune responders; rate ratio of 4.04 (1.83, 8.92), p<0.001.

Conclusions One in eight children in our cohort experienced PIR despite sustained viral suppression. While the overall rate of AIDS/death was low, children with PIR had four-fold increase in risk of event as compared to immune responders.

Authors: European Pregnancy and Paediatric HIV Cohort Collaboration (EPPICC) Study Group

Published in: Aids. 2019;33(2):295-304.

Objectives The aim of this study was to investigate whether specific nucleoside reverse transcriptase inhibitor (NRTI) backbones are associated with risk of adverse pregnancy outcomes among pregnant women starting antiretroviral therapy (ART).

Design Seven observational studies across eight European countries of pregnancies in HIV-positive women.

Methods Individual-level data were pooled on singleton pregnancies conceived off-ART in which a single combination ART regimen was initiated at least 2 weeks before delivery, and ending in a live birth in 2008-2014. Preterm delivery (PTD) was defined as less than 37 gestational weeks and small-for-gestational-age (SGA) as less than 10th percentile according to INTERGROWTH standards. Poisson regression models were fitted to investigate associations between NRTI backbones and PTD/SGA.

Results Out of 7193 pregnancies, 45% (3207) were in UK/Ireland, 44% (3134) in Ukraine. 10% (722/7193) of deliveries were preterm and 11.1% (785/7089) of newborns SGA. The most common NRTI backbones were zidovudine (ZDV)-lamivudine (3TC) (71%), tenofovir (TDF)-XTC (16%) and abacavir (ABC)-3TC (10%) with TDF-containing backbone use increasing over time. Overall, 77% of regimens contained ritonavir-boosted lopinavir (LPV/r). There was no association between NRTI backbone and PTD in main adjusted analyses [adjusted prevalence ratios (aPRs) 0.97 (95% confidence interval, 95% CI 0.73-1.28] for ABC-3TC and aPR 1.06 (95% CI 0.83-1.35) for TDF-XTC, both vs. ZDV-3TC) or in 4720 pregnancies on LPV/r [aPR 1.03 (95% CI 0.74-1.43) for ABC-3TC and aPR 1.16 [0.85-1.57] for TDF-XTC, both vs. ZDV-3TC]. Infants exposed to ABC-3TC or TDF-XTC in utero were less likely to be SGA than those exposed to ZDV-3TC [aPR 0.72 (95% CI 0.53-0.97) and aPR 0.70 (95% CI 0.53-0.93), respectively].

Conclusion Results support the safety of TDF-XTC backbones initiated in pregnancy with respect to gestation length and birthweight.

Authors: Martinez de Tejada B; European Pregnancy and Paediatric HIV Cohort Collaboration Study Group.

Published in: J Acquir Immune Defic Syndr. 2019;80(3):316-324

Background To investigate the association between efavirenz (EFV) use during conception or first trimester (T1) of pregnancy and the occurrence of birth defects.

Setting Seven observational studies of pregnant HIV-positive women across 13 European countries and Thailand.

Methods Individual-level data were pooled on singleton pregnancies included in participating cohorts in 2002-2015. Birth defects were coded according to ICD-10 and the EUROCAT classification. We performed mixed-effects logistic regression models to assess the association between EFV exposure in utero and likelihood of birth defects.

Results We included 24,963 live births from 21,093 women. At conception, 30.2% (7537) women were on a non-EFV-based regimen, 4.8% (1200) on EFV, and 65% (16,226) were unexposed to antiretroviral therapy (ART). There were 412 infants with ≥1 birth defect, a prevalence of 1.65% (95% confidence interval: 1.50 to 1.82). Limb/musculoskeletal and congenital heart defects were the most common defects reported. Birth defects were present in 2.4%, 1.6%, and 1.3% of infants exposed to non-EFV, EFV, and unexposed to ART during conception/T1 (P = 0.135), respectively. The association between exposure to ART during conception/T1 and birth defects remained nonsignificant in adjusted analyses, as did exposure to EFV versus non-EFV (adjusted odds ratio 0.61; 95% confidence interval: 0.36 to 1.03, P = 0.067). Among the 21 birth defects in 19 infants on EFV, no neural tube defects were reported.

Conclusions Prevalence of birth defects after exposure to EFV-based compared with non-EFV-based ART in conception/T1 was not statistically different in this multicohort study, and even lower. EFV is at least as safe as other ART drugs currently recommended for antenatal use.

Authors: Chan MK, Goodall R, Judd A, et al.

Published in: Aids. 2019; 33(7):1155-1165

Objective To identify predictors of faster time to virological suppression among infants starting combination antiretroviral therapy (cART) early in infancy.

Design Cohort study of infants from Europe and Thailand included in studies participating in the European Pregnancy and Paediatric HIV Cohort Collaboration (EPPICC).

Methods Infants with perinatal HIV starting cART aged <6 months with ≥1 viral load (VL) measurement within 15 months of cART initiation were included. Multivariable interval-censored flexible parametric proportional hazards models were used to assess predictors of faster virological suppression, with timing of suppression assumed to lie in the interval between last VL≥400 and first VL<400copies/ml.

Results Of 420 infants, 59% were female and 56% from Central/Western Europe, 26% UK/Ireland, 15% Eastern Europe and 3% Thailand; 46% and 54% started a boosted protease inhibitor- or non-nucleoside reverse transcriptase inhibitor- based regimen, respectively. At cART initiation, the median age, CD4% and VL were 2.9 (IQR:1.4-4.1) months, 34 (IQR:24-45)% and 5.5 (IQR:4.5-6.0) log10copies/ml, respectively. Overall, an estimated 89% (95%CI:86-92%) achieved virological suppression within 12 months of cART start. In multivariable analysis, younger age (aHR:0.84 per month older; P < 0.001), higher CD4% (aHR:1.11 per 10% higher; P = 0.010) and lower log10 VL (aHR:0.85 per log10 higher; P < 0.001) at cART initiation independently predicted faster virological suppression.

Conclusion We observed a significant independent effect of age at cART initiation, even within a narrow 6 months window from birth. These findings support the earliest feasible cART initiation in infants and suggest that early therapy influences key virological and immunological parameters that could have important consequences for long term health.

Authors: Judd A, Chappell E, Turkova A; for European Pregnancy and Paediatric HIV Cohort Collaboration (EPPICC) Study Group in EuroCoord.

Published in: PLoS Med. 2018;15(1): e1002491

Background Published estimates of mortality and progression to AIDS as children with HIV approach adulthood are limited. We describe rates and risk factors for death and AIDS-defining events in children and adolescents after initiation of combination antiretroviral therapy (cART) in 17 middle- and high-income countries, including some in Western and Central Europe (W&CE), Eastern Europe (Russia and Ukraine), and Thailand.

Methods and Findings Children with perinatal HIV aged <18 years initiating cART were followed until their 21st birthday, transfer to adult care, death, loss to follow-up, or last visit up until 31 December 2013. Rates of death and first AIDS-defining events were calculated. Baseline and time-updated risk factors for early/late (≤/>6 months of cART) death and progression to AIDS were assessed. Of 3,526 children included, 32% were from the United Kingdom or Ireland, 30% from elsewhere in W&CE, 18% from Russia or Ukraine, and 20% from Thailand. At cART initiation, median age was 5.2 (IQR 1.4–9.3) years; 35% of children aged <5 years had a CD4 lymphocyte percentage <15% in 1997–2003, which fell to 15% of children in 2011 onwards (p < 0.001). Similarly, 53% and 18% of children ≥5 years had a CD4 count <200 cells/mm³ in 1997–2003 and in 2011 onwards, respectively (p < 0.001). Median follow-up was 5.6 (2.9–8.7) years. Of 94 deaths and 237 first AIDS-defining events, 43 (46%) and 100 (42%) were within 6 months of initiating cART, respectively. Multivariable predictors of early death were: being in the first year of life; residence in Russia, Ukraine, or Thailand; AIDS at cART start; initiating cART on a nonnucleoside reverse transcriptase inhibitor (NNRTI)-based regimen; severe immune suppression; and low BMI-for-age z-score. Current severe immune suppression, low current BMI-for-age z-score, and current viral load >400 c/mL predicted late death. Predictors of early and late progression to AIDS were similar. Study limitations include incomplete recording of US Centers for Disease Control (CDC) disease stage B events and serious adverse events in some countries; events that were distributed over a long time period, and that we lacked power to analyse trends in patterns and causes of death over time.

Conclusions In our study, 3,526 children and adolescents with perinatal HIV infection initiated antiretroviral therapy (ART) in countries in Europe and Thailand. We observed that over 40% of deaths occurred ≤6 months after cART initiation. Greater early mortality risk in infants, as compared to older children, and in Russia, Ukraine, or Thailand as compared to W&CE, raises concern. Current severe immune suppression, being underweight, and unsuppressed viral load were associated with a higher risk of death at >6 months after initiation of cART.

Authors: Favarato G, Bailey H, Burns F, et al.

Published in: Eur J Public Health. 2018;28(1):55-60

Authors: European Pregnancy and Paediatric HIV Cohort Collaboration (EPPICC) Study Group in EuroCoord.

Published in: Clin Infect Dis. 2018;66(4):594-603.

Background Global data on durability of first-line antiretroviral therapy (ART) in children with HIV is limited. We assessed time to switch to second-line therapy in 16 European countries and Thailand.

Methods Children <18-years initiating combination ART (≥2 nucleoside reverse transcriptase inhibitor (NRTI) plus non-NRTI (NNRTI) or boosted-protease inhibitor (PI)) were included. Switch to second-line was defined as: (i) change across drug class (PI to NNRTI or vice versa) or within PI-class plus change of ≥1 NRTI; (ii) change from single to dual PI; or (iii) addition of a new drug class. Cumulative incidence of switch was calculated with death and loss-to-follow-up as competing risks.

Results Of 3,668 children included, median [IQR] age at ART initiation was 6.1 [1.7,10.5] years. Initial regimens were 32% PI, 34% nevirapine (NVP), 33% efavirenz-based. Median duration of follow-up from ART start was 5.4 [2.9,8.3] years. Cumulative incidence of switch at 5 years was 21% (95% CI 20, 23), with lowest incidence in Russia/Ukraine and highest in UK/Ireland. Median time to switch was 30 [15, 58] months, two-thirds of switches were related to treatment failure. In multivariable analysis, older age, severe immunosuppression and higher viral load at ART start, and NVP-based initial regimens were associated with increased risk of switch. Among those switched, 65% had viral load <400c/mL at 12-months after start of second-line ART.

Conclusions One in five children switched to second-line by 5 years of ART, with two-thirds failure related. Advanced HIV, older age and NVP-based regimens were associated with increased risk of switch.

Authors: European Pregnancy and Paediatric HIV Cohort Collaboration (EPPICC) study group in EuroCoord.

Published in: Eur J Clin Pharmacol. 2017;73(4):463-468

Authors: Schomaker M, Leroy V, Wolfs T, et al. On behalf of theIeDEA West and Southern Africa regional collaborations and COHERE in EuroCoord.

Published in: Int J Epidemiol. 2017;46(2):453-465.

Background: There is limited knowledge about the optimal timing of antiretroviral treatment initiation in older children and adolescents.

Methods: A total of 20 576 antiretroviral treatment (ART)-naïve patients, aged 1-16 years at enrolment, from 19 cohorts in Europe, Southern Africa and West Africa, were included. We compared mortality and growth outcomes for different ART initiation criteria, aligned with previous and recent World Health Organization criteria, for 5 years of follow-up, adjusting for all measured baseline and time-dependent confounders using the g-formula.

Results: Median (1st;3rd percentile) CD4 count at baseline was 676 cells/mm³(394; 1037) (children aged ≥ 1 and < 5 years), 373 (172; 630) (≥ 5 and < 10 years) and 238 (88; 425) (≥ 10 and < 16 years). There was a general trend towards lower mortality and better growth with earlier treatment initiation. In children < 10 years old at enrolment, by 5 years of follow-up there was lower mortality and a higher mean height-for-age z-score with immediate ART initiation versus delaying until CD4 count < 350 cells/mm³ (or CD4% < 15% or weight-for-age z-score < -2) with absolute differences in mortality and height-for-age z-score of 0.3% (95% confidence interval: 0.1%; 0.6%) and -0.08 (-0.09; -0.06) (≥ 1 and < 5 years), and 0.3% (0.04%; 0.5%) and -0.07 (-0.08; -0.05) (≥ 5 and < 10 years). In those aged > 10 years at enrolment we did not find any difference in mortality or growth with immediate ART initiation, with estimated differences of -0.1% (-0.2%; 0.6%) and -0.03 (-0.05; 0.00), respectively. Growth differences in children aged < 10 years persisted for treatment thresholds using higher CD4 values. Regular follow-up led to better height and mortality outcomes.

Conclusions: Immediate ART is associated with lower mortality and better growth for up to 5 years in children < 10 years old. Our results on adolescents were inconclusive.

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

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

Authors: Adedeji O Majekodunmi, Claire Thorne, Ruslan Malyuta, Alla Volokha, Robin E Callard, Nigel J Klein, Joanna Lewis, European Paediatric HIV/HCV Co-infection Study group in the European Pregnancy and Paediatric HIV Cohort Collaboration and the Ukraine Paediatric HIV Cohort Study in EuroCoord

Published in: Pediatr Infect Dis J. 2017 May;36(5):e123-e129. doi: 10.1097/INF.0000000000001478. PMID: 28403051; PMCID: PMC5380220.

Authors: Bailey H, Malyuta R, Townsend C, Cortina Borja M, Thorne C for the Ukraine European Collaborative Study in EuroCoord.

Published in: Reprod Health. 2016;22(3):13-27.

Background Perinatal depression among HIV-positive women has negative implications for HIV-related and other maternal and infant outcomes. The aim of this study was to investigate the burden and correlates of perinatal depression among HIV-positive women in Ukraine, a lower middle income country with one of the largest HIV-positive populations in Europe.

Methods Cross-sectional surveys nested within the Ukraine European Collaborative Study were conducted of HIV-positive women at delivery and between 1 and 12 months postpartum. Depressive symptoms in the previous month were assessed using a self-report screening tool. Other data collected included demographics, antiretroviral therapy (ART)-related self-efficacy, and perceptions of risks/benefits of interventions to prevent mother-to-child transmission (PMTCT). Characteristics of women with and without a positive depression screening test result were compared using Fisher’s exact test and χ2 test for categorical variables.

Results A quarter (27% (49/180) antenatally and 25% (57/228) postnatally) of participants screened positive for depressive symptoms. Antenatal risk factors were living alone (58% (7/12) vs. 25% (42/167) p = 0.02), being somewhat/terribly bothered by ART side effects (40% (17/43) vs. 23% (30/129) not /only slightly bothered, p = 0.05) and having lower ART-related self-efficacy (43% (12/28) vs. 23% (25/110) with higher self-efficacy, p = 0.05). Postnatally, single mothers were more likely to screen positive (44% (20/45) vs. 21% (18/84) of cohabiting and 19% (19/99) of married women, p < 0.01) as were those unsure of the effectiveness of neonatal prophylaxis (40% (20/45) vs. 18% (28/154) sure of effectiveness, p < 0.01), those worried that neonatal prophylaxis could harm the baby (30% (44/146) vs. 14% (10/73) not worried p < 0.01) and those not confident to ask for help with taking ART (48% (11/23) vs. 27% (10/37) fairly confident and 15 % (4/26) confident that they could do this). Of women who reported wanting help for their depressive symptoms, 82% (37/45) postnatally but only 31% (12/39) antenatally were already accessing peer counselling, treatment adherence programmes, support groups or social services.

Conclusions A quarter of women screened positive for depression. Results highlight the need for proactive strategies to identify depressive symptoms, and an unmet need for provision of mental health support in the perinatal period for HIV-positive women in Ukraine.

Authors: Turkova A, Chappell E, Chalermpantmetagul S, et al.

Published in: Int J Tuberc Lung Dis 2016;20(11):1448-1456.

Setting Centres participating in the Paediatric European Network for Treatment of AIDS (PENTA), including Thailand and Brazil.

Objective To describe the incidence, presentation, treatment and treatment outcomes of tuberculosis (TB) in human immunodeficiency virus (HIV) infected children.

Design Observational study of TB diagnosed in HIV-infected children in 2011–2013.

Results Of 4265 children aged <16 years, 127 (3%) were diagnosed with TB: 6 (5%) in Western Europe, 80 (63%) in Eastern Europe, 27 (21%) in Thailand and 14 (11%) in Brazil, with estimated TB incidence rates of respectively 239, 982, 1633 and 2551 per 100 000 person-years (py). The majority (94%) had acquired HIV perinatally. The median age at TB diagnosis was 6.8 years (interquartile range 3.0–11.5). Over half (52%) had advanced/severe World Health Organization stage immunodeficiency; 67 (53%) were not on antiretroviral therapy (ART) at TB diagnosis. Preventive anti-tuberculosis treatment was given to 23% (n = 23) of 102 children diagnosed with HIV before TB. Eleven children had unfavourable TB outcomes: 4 died, 5 did not complete treatment, 1 had recurrent TB and 1 had an unknown outcome. In univariable analysis, previous diagnosis of acquired immune-deficiency syndrome, not being virologically suppressed on ART at TB diagnosis and region (Brazil) were significantly associated with unfavourable TB outcomes.

Conclusion Most TB cases were from countries with high TB prevalence. The majority (91%) had favourable outcomes. Universal ART and TB prophylaxis may reduce missed opportunities for TB prevention.

Authors: European Pregnancy and Paediatric HIV Cohort Collaboration (EPPICC) study group in EuroCoord.

Published in: Antivir Ther. 2016; 21(4): 353-8

Authors: Ngo-Giang-Huong N, Wittkop L, Judd A, et al. For EuroCoord-CHAIN-EPPICC joint project study group.

Published in: BMC Infect Dis. 2016;16(1):654.

Authors: Aebi-Popp K, Bailey H, Malyuta R, Volokha A, Thorne C. Ukraine European Collaborative Study in EuroCoord.

Published in: BMC Pregnancy Childbirth. 2016;27;16:94

Authors: Writing group for the Kids to Adults Working Group and Data Management and Harmonisation Group in EuroCoord.

Published in: Euro Surveill.2016;21(10): 30162

Abstract Accurate ascertainment of the number of children living with human immunodeficiency virus (HIV) is important to plan paediatric and adolescent health services. In Europe, the first generation of perinatally HIV-infected survivors are transferring to adult care and their health needs are unknown. We undertook an online survey of HIV cohort studies participating in the EuroCoord Network of Excellence to ascertain the number of perinatally HIV-infected (pHIV) patients included, to compare it with those published by the European Centre for Disease Prevention and Control (ECDC) and the World Health Organization (WHO) and to assess the ability of countries to follow up pHIV patients after transfer to adult care. At the end of 2013, 16 countries in EuroCoord reported 8,229 pHIV patients in follow-up in cohorts, compared with 5,160 cumulative diagnoses reported by the ECDC in the same area. Follow-up of pHIV patients after transfer to adult care varied. It is likely that the number of diagnoses of perinatal HIV reported to ECDC is an underestimate, although this varies by country. Further work is needed to refine estimates and encourage follow-up in adult HIV cohorts to investigate long-term outcomes and improve the care of the next generation of children with HIV.

Authors: Turkova A, Giacomet V, Goetghebuer T, et al.

Published in: J Virus Erad. 2015;1(3):179-184

Methods HCV treatment data on children and young people aged <25 years with HIV/HCV co-infection were collected in a cohort collaboration of 11 European paediatric HIV cohorts. Factors associated with receipt of HCV treatment and with sustained virological response 24 weeks after treatment completion (SVR24) were explored.

Results Of 229 HIV/HCV co-infected patients, 22% had a history of AIDS and of 55 who were treated for HCV, 47 (85%) were receiving combined antiretroviral therapy. The overall HCV treatment rate was 24% (n=55) but it varied substantially between countries, with the highest rate being in Russia at 61% (30/49). Other factors associated with treatment receipt were older age [adjusted odds ratio (AOR) 5.24, 95% confidence interval (CI) 1.9–14.4, for 18–24-year-olds vs 11–17-year-olds, P=0.001] and advanced fibrosis (AOR 5.5, 95% CI 1.3–23.7; for ≥9.6 vs ≤7.2 kPa, P=0.02). Of 50 patients with known treatment outcomes, 50% attained SVR24. Of these, 16 (80%) had genotype (GT) 2,3 and 8 (29%) had GT 1,4 (P<0.001). After adjusting for genotype (GT 1,4 vs GT 2,3), females (P=0.003), patients with non-vertical HCV acquisition (P=0.002) and those with shorter duration of HCV (P=0.009) were more likely to have successful treatment outcomes.

Authors: Bailey H, Townsend C, Semenenko I, Malyuta R, Cortina-Borja, Thorne C; for the Ukraine European Collaborative Study in EuroCoord

Published in: BMC Public Health. 2014; 24(14):993

Background Poor adherence to antiretroviral therapy (ART) is associated with HIV disease progression and, during

pregnancy, increased mother-to-child transmission risk. In Ukraine, access to combination ART is expanding but data

on adherence are scarce.

Methods Cross-sectional surveys of HIV-positive women were conducted i) at delivery (on antenatal ART adherence)

and ii) during the first year postpartum (on ART adherence in the preceding four weeks). Factors associated with a

score ≤11 on the self-report Case Adherence Support Evaluation (CASE) index or ≥1 self-reported missed dose were

assessed using Fisher’s exact test.

Results Of 185 antenatal participants and 102 postnatal participants, median ages were 27.5 and 29.5 years

respectively: 28% (50/180) and 27% (26/98) reported an unplanned pregnancy, and 13% (24/179) and 17% (17/98) an

illicit drug-use history (excluding marijuana). One quarter (49/180 antenatally, 27/101 postnatally) screened positive for

depression. The proportion reporting ‘low’ ART-related self-efficacy (i.e. unable to do ≥1/5 ART-taking activities) was

20% (28/141) antenatally and 17% (11/66) postnatally. Antenatally, 14% (95% CI 10-21%) had a CASE score ≤11 and

35% (95% CI 28-42%) reported missing ≥1 dose. Factors associated with a CASE score ≤11 were unplanned pregnancy

(25% (12/48) vs. 11% (13/120) where planned, p = 0.03) and living with extended family (23% (13/57) vs. 10% (12/125)

living with partner/alone, p = 0.04). Self-report of ≥1 missed dose antenatally was additionally associated with

younger age (p = 0.03) and lower self-efficacy (50% (14/28) reported ≥1 missed dose vs. 28% (30/108) of those

with high self-efficacy, p = 0.04). Of 102 postnatal participants, 8% (95% CI 4-15%) had a CASE score ≤11 and 31%

(95% CI 22-41%) reported ≥1 missed dose. Of 11 women with low self-efficacy, 3 (27%) had a CASE score ≤11

compared with 3/55 (5%) of those with high self-efficacy (p = 0.05). Current smokers more commonly reported ≥1

missed dose postnatally (50% (13/26) vs. 25% (18/72) of non-smokers, p = 0.03).

Conclusions Our results highlight unmet needs for counselling and support. We identify some groups at risk of

poor ART adherence, including women with markers of social vulnerability and those with low ART-related

self-efficacy, who may benefit from targeted interventions.