EPPICC

18

Jun, 2017

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.

12

Dec, 2016

Prevalence of depressive symptoms in pregnant and postnatal HIV-positive women in Ukraine: a cross-sectional survey

 

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.

 

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20

Nov, 2016

Tuberculosis in HIV-infected children in Europe, Thailand and Brazil: paediatric TB-HIV EuroCoord study

 

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.

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12

Nov, 2016

Safety of darunavir and atazanavir in HIV-infected children in Europe and Thailand

 

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

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

Background Surveillance for mid- and long-term antiretroviral therapy (ART) toxicity in children is important for informing treatment guidelines. We assessed the safety of darunavir (DRV) and atazanavir (ATV), commonly used as second-line protease inhibitors following lopinavir/ritonavir, in Europe and Thailand.

Methods Cohorts contributed individual patient data on adverse events (AE) in those aged <18 years taking DRV and ATV, respectively, to 02/2014. Rates of Division of AIDS (DAIDS) grade ≥3 laboratory AEs were calculated.

Results Of 431 patients on DRV and 372 on ATV, 317 (74%) and 301 (81%), respectively, had weight and dose data available, of whom 56 (18%) and 33 (9%) took the drugs at a non-approved age or dose. Median age at DRV and ATV start was 14.8 years (IQR 12.8-16.1) and 13.5 years (11.4-15.2); 43% and 26% had received ≥8 ART drugs previously. Overall rates of grade ≥3 AEs for absolute neutrophils, total cholesterol, triglycerides, pancreatic amylase, lipase and alanine aminotransferase (ALT) were ≤3/100 person-years (PY) on approved doses of both drugs, but 66/100 PY (95% CI 52, 84) for bilirubin after <12 months on ATV declining to 32/100 PY (95% CI 23, 44) after >24 months. Five serious drug-related clinical AEs were reported in four patients on ATV (one discontinued) and three in three patients on DRV (all discontinued), and did not substantially differ in those on approved compared to non-approved doses. Proportions on the drugs at last follow-up were 89% (383/431) for DRV and 81% (301/372) for ATV (including 73/92 with grade ≥3 hyperbilirubinaemia).

Conclusions AEs were few in number and comparable for the two drugs, with the exception of high rates of hyperbilirubinaemia for ATV; few patients discontinued due to toxicity.

8

Nov, 2016

Prevalence and effect of pre-treatment drug resistance on the virological response to antiretroviral treatment initiated in HIV-infected children – a EuroCoord-CHAIN-EPPICC joint project.

 

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.

Background Few studies have evaluated the impact of pre-treatment drug resistance (PDR) on response to combination antiretroviral treatment (cART) in children. The objective of this joint EuroCoord-CHAIN-EPPICC/PENTA project was to assess the prevalence of PDR mutations and their association with virological outcome in the first year of cART in children.

Methods HIV-infected children <18 years initiating cART between 1998 and 2008 were included if having at least one genotypic resistance test prior to cART initiation. We used the World Health Organization 2009 resistance mutation list and Stanford algorithm to infer resistance to prescribed drugs. Time to virological failure (VF) was defined as the first of two consecutive HIV-RNA > 500 copies/mL after 6 months cART and was assessed by Cox proportional hazards models. All models were adjusted for baseline demographic, clinical, immunology and virology characteristics and calendar period of cART start and initial cART regimen.

Results Of 476 children, 88 % were vertically infected. At cART initiation, median (interquartile range) age was 6.6 years (2.1–10.1), CD4 cell count 297 cells/mm3(98–639), and HIV-RNA 5.2 log10copies/mL (4.7–5.7). Of 37 children (7.8 %, 95 % confidence interval (CI), 5.5–10.6) harboring a virus with ≥1 PDR mutations, 30 children had a virus resistant to ≥1 of the prescribed drugs. Overall, the cumulative Kaplan-Meier estimate for virological failure was 19.8 % (95 %CI, 16.4–23.9). Cumulative risk for VF tended to be higher among children harboring a virus with PDR and resistant to ≥1 drug prescribed than among those receiving fully active cART: 32.1 % (17.2–54.8) versus 19.4 % (15.9–23.6) (P = 0.095). In multivariable analysis, age was associated with a higher risk of VF with a 12 % reduced risk per additional year (HR 0.88; 95 %CI, 0.82–0.95; P < 0.001).

Conclusions PDR was not significantly associated with a higher risk of VF in children in the first year of cART. The risk of VF decreased by 12 % per additional year at treatment initiation which may be due to fading of PDR mutations over time. Lack of appropriate formulations, in particular for the younger age group, may be an important determinant of virological failure.

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27

Apr, 2016

High prevalence of herpes simplex virus (HSV)- type 2 co-infection among HIVpositive women in Ukraine, but no increased HIV mother-to-child transmission risk

 

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

Background Over 3500 HIV-positive women give birth annually in Ukraine, a setting with high prevalence of sexually transmitted infections. Herpes simplex virus Type 2 (HSV-2) co-infection may increase HIV mother-to-child transmission (MTCT) risk. We explored factors associated with HSV-2 seropositivity among HIV-positive women in Ukraine, and its impact on HIV MTCT.

Methods Data on 1513 HIV-positive women enrolled in the Ukraine European Collaborative Study from 2007 to 2012 were analysed. Poisson and logistic regression models respectively were fit to investigate factors associated with HSV-2 seropositivity and HIV MTCT.

Results Median maternal age was 27 years (IQR 24–31), 53 % (796/1513) had been diagnosed with HIV during their most recent pregnancy and 20 % had a history of injecting drugs. Median antenatal CD4 count was 430 cells/mm3 (IQR 290–580). Ninety-six percent had received antiretroviral therapy antenatally. HSV-2 seroprevalence was 68 % (1026/1513). In adjusted analyses, factors associated with HSV-2 antibodies were history of pregnancy termination (APR 1.30 (95 % CI 1.18–1.43) for ≥2 vs. 0), having an HIV-positive partner (APR 1.15 (95 % CI 1.05–1.26) vs partner’s HIV status unknown) and HCV seropositivity (APR 1.23 (95 % CI 1.13–1.35)). The overall HIV MTCT rate was 2.80 % (95 % CI 1.98–3.84); no increased HIV MTCT risk was detected among HSV-2 seropositive women after adjusting for known risk factors (AOR 1.43 (95 % CI 0.54–3.77).

Conclusion No increased risk of HIV MTCT was detected among the 68 % of HIV-positive women with antibodies to HSV-2, in this population with an overall HIV MTCT rate of 2.8 %. Markers of ongoing sexual risk among HIV-positive HSV-2 seronegative women indicate the importance of interventions to prevent primary HSV-2 infection during pregnancy in this high-risk group.

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10

Mar, 2016

Children and young people with perinatal HIV in Europe: epidemiological situation in 2014 and implications for the future

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

Published inEuro 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.

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18

Dec, 2014

Adherence to antiretroviral therapy in pregnancy and during the first year post-partum in HIV-positive women in Ukraine

 

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.

 

 

 

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18

Jul, 2014

Uptake and outcomes of HCV treatment in children and young adults with HIV/HCV co-infection in Europe

 

Authors: Turkova A; for the European Paediatric HIV/HCV Co-infection Study Group in the European Pregnancy and Paediatric HIV Cohort Collaboration in EuroCoord.

Published in: 20th International AIDS Conference (AIDS 2014), July 20th-25th 2014, Melbourne, Australia.

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18

Jul, 2014

Children living with HIV in Ukraine: response to antiretroviral therapy (ART) and duration of first-line regimens

 

Authors: Bagkeris E, Bailey H, Malyuta R, Volokha A, Thorne C

Published in: 6th International Workshop on HIV Pediatrics, July 18th-19th  2014, Melbourne, Australia.

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