Publications

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.

11

Nov, 2016

Interventions to improve treatment, retention and survival outcomes for adolescents with perinatal HIV-1 in high- and middle-income countries: Moving on up.

 

Authors: Judd A, Sohn A, Collins J.

Published in: Curr Opin HIV AIDS 2016;11(5):477-486.

Purpose of review There is an increasing number of deaths among adult survivors of perinatal HIV. Multiple and complex factors drive this mortality, including problems with retention in care and adherence during adolescence, coupled with the critical period of transition from paediatric to adult care, increasing their risk of treatment failure and severe immunosuppression. We reviewed studies that evaluated the impact of service delivery interventions to improve the health of perinatally infected adolescents living with HIV (P-ALHIV) to gain insight into what might help them survive the vulnerable period of adolescence.

Recent findings Youth-focused health services and individual-level interventions may improve P-ALHIV adherence and retention in care. However, there have been few studies, many with small sample sizes and with short durations of follow-up that end before the transition period. Studies from other childhood-onset chronic diseases are similarly limited.

Summary Further studies are urgently needed to identify optimal intervention strategies to reduce mortality and poor outcomes as the adolescent population expands and ages into adult care. Until we have a more robust evidence base, programmes can develop transition plans based on best practice recommendations to optimize the health and longevity of ALHIV in adulthood.

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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2

Nov, 2016

The ZIKAction Kick-Off Meeting was a success!

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The ZIKAction Kick-Off Meeting was held in Kingston, Jamaica at the University of West Indies from October 30th to November 1st.

zikactionkomphoto

Thank you all for coming!!

This project has received funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement No 734857.

1

Nov, 2016

Kaposi Sarcoma risk in HIV-infected children and adolescents on combination antiretroviral therapy from Eastern Africa, Southern Africa, Europe and Asia.

 

Authors: The International Epidemiologic Databases to Evaluate AIDS Southern Africa, the Collaboration of Observational HIV Epidemiological Research in Europe in EuroCoord and the TREAT Asia Pediatric HIV Observational Database study group.  

Published in: Clinical Infectious Diseases, in press.

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