Publications

29

Apr, 2018

Long-term trends in mortality and AIDS-defining events after combination ART initiation among children and adolescents with perinatal HIV infection in 17 middle- and high-income countries in Europe and Thailand: A cohort study

 

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.

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29

Apr, 2018

Global Trends in CD4 Cell Count at the Start of Antiretroviral Therapy: Collaborative Study of Treatment Programs.

 

Authors: IeDEA and COHERE Cohort Collaborations.

Published in: Clin Infect Dis. 2018;66(6):893-903.

Background Early initiation of combination antiretroviral therapy (cART), at higher CD4 cell counts, prevents disease progression and reduces sexual transmission of human immunodeficiency virus (HIV). We describe the temporal trends in CD4 cell counts at the start of cART in adults from low-income, lower-middle-income, upper-middle-income, and high-income countries (LICs, LMICs, UMICs, and HICs, respectively).

Methods We included HIV-infected individuals aged ≥16 years who started cART between 2002 and 2015 in a clinic participating in the International epidemiology Databases to Evaluate AIDS (IeDEA) or the Collaboration of Observational HIV Epidemiological Research in Europe (COHERE). Missing CD4 cell counts at the start of cART were estimated through multiple imputation. Weighted mixed-effect models were used to smooth trends in median CD4 cell counts.

Results A total of 951855 adults from 16 LICs, 11 LMICs, 9 UMICs, and 19 HICs were included. Overall, the modeled median CD4 cell count at the start of cART increased from 2002 to 2015, from 78/µL (95% confidence interval, 58–104/µL) to 287/µL (250–328/µL) in LICs, from 99/µL (71–140/µL) to 234/µL (192–285/µL) in LMICs, from 71/µL (49–104/µL) to 311/µL (255–379/µL) in UMICs, and from 161/µL (143–181/µL) to 327/µL (286–372/µL) in HICs. In LICs, LMICs, and UMICs, the increase was more pronounced in women; in HICs, the opposite was observed.

Conclusions Median CD4 cell counts at the start of cART increased in all income groups, but generally remained below 350/μL in 2015. Substantial additional efforts and resources are required to achieve earlier diagnosis, linkage to care, and initiation of cART.

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28

Apr, 2018

Tr@inforPedHIV Guatemala: a big thanks to all participants

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foto-grupo-guatemala-2018The 3-day course in Guatemala has come to a close. Around 100 frontline healthcare professionals caring for HIV infected children from Guatemala, San Salvador, Ecuador, Panama, Mexico, Nicaragua and Costa Rica met in Antigua, 45 kilometres from Guatemala City, in order to acquire new knowledge and share their experience and know-how in the treatment and care of Pediatric HIV. The course agenda foresaw: epidemiology and elimination of perinatal transmission, HIV evolution and ART treatment in children and adolescents, co-infection and HIV in adolescents. Through case studies and group discussion, participants had a unique opportunity to grow professionally and advance knowledge in their countries.

We would like to thank all the faculty for their involvement and their passion in promoting scientific knowledge in the pediatric HIV field. We also wish to extend our warmest thanks to all participants, and to beautiful Guatemala for welcoming us!

27

Apr, 2018

10th annual International Workshop on HIV Pediatrics 2018 – Final call for abstract submission

 

The 10th annual International Workshop on HIV Pediatrics 2018 is fast approaching.

Do not miss the opportunity to submit an abstract on your research in the following fields:

  • Prevention of mother-to-child HIV transmission, including HIV-exposed uninfected children;
  • Antiretroviral treatment of pediatric HIV infection;
  • Complications of HIV and its treatment in children;
  • Co-infections in HIV-infected children;
  • Comprehensive pediatric HIV care;
  • HIV infection and adolescents (perinatally and behaviourally acquired);
  • Implementating science research on PMTCT and pediatric treatment programs.

Co-submission of your abstract for both the Pediatrics workshop as well as the 22nd International AIDS Conference (AIDS 2018) is possible. Abstract submission closes on Friday 4 May 2018.

For more information, please visit the website.
The workshop is scheduled on 20 and 21 July 2018, Amsterdam, the Netherlands.

26

Apr, 2018

4th HIV Exposed Uninfected (HEU) child and adolescent workshop, Amsterdam – The Netherlands, July 22nd 2018

 

The International AIDS Society’s CIPHER initiative in partnership with WHO, UNICEF, PHACS and MassGeneral Hospital for Children will host the 4th HEU Child and Adolescent Workshop in Amsterdam, the Netherlands on 22 July 2018. This is an official pre-conference of the 22nd International AIDS Conference (AIDS 2018).

The workshop will offer an exciting half-day session of expert presentations, interactive panel discussions and open dialogue on HIV-exposed uninfected (HEU) children and adolescents.

Enrollment for this pre-conference will be on a first-come first-served basis, and open only to delegates who are registered for AIDS 2018. Individuals who are interested in attending are encouraged to sign up in order to receive meeting updates. If you are not registered for AIDS 2018 and are interested in attending, or if you have any questions about the workshop, please contact the organizers at cipher@iasociety.org.

26

Apr, 2018

Plasma and CSF pharmacokinetics of meropenem in neonates and young infants : results from the NeoMero studies

 

Authors: Germovesk E, Lutsar I, Kipepr K, et al.; for NeoMero Consortium

Published in: J Antimicrob Chemother. 2018;73(7):1908-1916

Background Sepsis and bacterial meningitis are major causes of mortality and morbidity in neonates and infants. Meropenem a broad-spectrum antibiotic, is not licensed for use in neonates and infants below 3 months of age and sufficient information on its plasma and CSF disposition and dosing in neonates and infants is lacking.

Objectives To determine plasma and CSF pharmacokinetics of meropenem in neonates and young infants and the link between pharmacokinetics and clinical outcomes in babies with late-onset sepsis (LOS).

Methods Data were collected in two recently conducted studies, i.e. Neo-Mero-1 (neonatal LOS) and Neo-Mero-2 (neonatal meningitis). Optimally timed plasma samples (n = 401) from 167 patients and opportunistic CSF samples (n = 78) from 56 patients were analysed.

Results A one-compartment model with allometric scaling and fixed maturation gave adequate fit to both plasma and CSF data; the CL and volume (standardized to 70 kg) were 16.7 (95% CI 14.7, 18.9) L/h and 38.6 (95% CI 34.9, 43.4) L, respectively. CSF penetration was low (8%), but rose with increasing CSF protein, with 40% penetration predicted at a protein concentration of 6 g/L. Increased infusion time improved plasma target attainment, but lowered CSF concentrations. For 24 patients with culture-proven Gram-negative LOS, pharmacodynamic target attainment was similar regardless of the test-of-cure visit outcome.

Conclusions Simulations showed that longer infusions increase plasma PTA but decrease CSF PTA. CSF penetration is worsened with long infusions so increasing dose frequency to achieve therapeutic targets should be considered.

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26

Apr, 2018

Surveillance for control of antimicrobial resistance

 

Authors: Tacconelli E, Sifakis F, Harbarth S, et al; for EPI-Net COMBACTE-MAGNET Group

Published in: Lancet Infect Dis. 2018;18(3):e99-e106.

Abstract Antimicrobial resistance poses a growing threat to public health and the provision of health care. Its surveillance should provide up-to-date and relevant information to monitor the appropriateness of therapy guidelines, antibiotic formulary, antibiotic stewardship programmes, public health interventions, infection control policies, and antimicrobial development. In Europe, although the European Antimicrobial Resistance Surveillance Network provides annual reports on monitored resistant bacteria, national surveillance efforts are still fragmented and heterogeneous, and have substantial structural problems and issues with laboratory data. Most incidence and prevalence data cannot be linked with relevant epidemiological, clinical, or outcome data. Genetic typing, to establish whether trends of antimicrobial resistance are caused by spread of resistant strains or by transfer of resistance determinants among different strains and species, is not routinely done. Furthermore, laboratory-based surveillance using only clinical samples is not likely to be useful as an early warning system for emerging pathogens and resistance mechanisms. Insufficient coordination of surveillance systems of human antimicrobial resistance with animal surveillance systems is even more concerning. Because results from food surveillance are considered commercially sensitive, they are rarely released publicly by regulators. Inaccurate or incomplete surveillance data delay a translational approach to the threat of antimicrobial resistance and inhibit the identification of relevant target microorganisms and populations for research and the revitalisation of dormant drug-discovery programmes. High-quality, comprehensive, and real-time surveillance data are essential to reduce the burden of antimicrobial resistance. Improvement of national antimicrobial resistance surveillance systems and better alignment between human and veterinary surveillance systems in Europe must become a scientific and political priority, coordinated with international stakeholders within a global approach to reduce the burden of antimicrobial resistance.

26

Apr, 2018

Effects of clinical pathway implementation on antibiotic prescription for pediatric community-acquired pneumonia

 

Authors: Donà D, Zingarella S, Gastaldi A, et al.

Published in: PLoS One. 2018;13(2):e0193581. 

Background Italian pediatric antimicrobial prescription rates are among the highest in Europe. As a first step in an Antimicrobial Stewardship Program, we implemented a Clinical Pathway (CP) for Community Acquired Pneumonia with the aim of decreasing overall prescription of antibiotics, especially broad-spectrum.

Materials and Methods The CP was implemented on 10/01/2015. We collected antibiotic prescribing and outcomes data from children aged 3 months-15 years diagnosed with CAP from 10/15/2014 to 04/15/2015 (pre-intervention period) and from 10/15/2015 to 04/15/2016 (post-intervention period). We assessed antibiotic prescription differences pre- and post-CP, including rates, breadth of spectrum, and duration of therapy. We also compared length of hospital stay for inpatients and treatment failure for inpatients and outpatients. Chi-square and Fisher’s exact test were used to compare categorical variables and Wilcoxon rank sum test was used to compare quantitative outcomes.

Results 120 pre- and 86 post-intervention clinic visits were identified with a diagnosis of CAP. In outpatients, we observed a decrease in broad-spectrum regimens (50% pre-CP vs. 26.8% post-CP, p = 0.02), in particular macrolides, and an increase in narrow-spectrum (amoxicillin) post-CP. Post-CP children received fewer antibiotic courses (median DOT from 10 pre-CP to 8 post-CP, p<0.0001) for fewer days (median LOT from 10 pre-CP to 8 post-CP, p<0.0001) than their pre-CP counterparts. Physicians prescribed narrow-spectrum monotherapy more frequently than broad-spectrum combination therapy (DOT/LOT ratio 1.157 pre-CP vs. 1.065 post-CP). No difference in treatment failure was reported before and after implementation (2.3% pre-CP vs. 11.8% post-CP, p = 0.29). Among inpatients we also noted a decrease in broad-spectrum regimens (100% pre-CP vs. 66.7% post-CP, p = 0.02) and the introduction of narrow-spectrum regimens (0% pre-CP vs. 33.3% post-CP, p = 0.02) post-CP. Hospitalized patients received fewer antibiotic courses post-CP (median DOT from 18.5 pre-CP to 10 post-CP, p = 0.004), while there was no statistical difference in length of therapy (median LOT from 11 pre-CP to 10 post-CP, p = 0.06). Days of broad spectrum therapy were notably lower post-CP (median bsDOT from 17 pre-CP to 4.5 post-CP, p <0.0001). No difference in treatment failure was reported before and after CP implementation (16.7% pre-CP vs. 15.4% post-CP, p = 1).

Conclusions Introduction of a CP for CAP in a Pediatric Emergency Department led to reduction of broad-spectrum antibiotic prescriptions, of combination therapy and of duration of treatment both for outpatients and inpatients.

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26

Apr, 2018

Strategies for prevention of mother-to-child transmission adopted in the “real-world” setting: data from the italian register for HIV-1 infection in children.

 

Authors: Chiappini E, Galli L, Lisi C, et al.

Published in: J Acquir Immune Defic Syndr. 2018;79(1):54-61.

Background Strategies for prevention of HIV-1 mother-to-child transmission (PMTCT) have been continuously optimized. However, cases of vertical transmission continue to occur in high-income countries.

Objectives To investigate changes in PMTCT strategies adopted by Italian clinicians over time and to evaluate risk factors for transmission.

Methods Data from mother-child pairs prospectively collected by the Italian Register, born in Italy in 1996-2016, were analyzed. Risk factors for MTCT were explored by logistic regression analyses.

Results Six thousand five hundred three children (348 infections) were included. In our cohort, the proportion of children born to foreign mothers increased from 18.3% (563/3078) in 1996%-2003% to 66.2% (559/857) in 2011-2016 (P < 0.0001). Combination neonatal prophylaxis use significantly (P < 0.0001) increased over time, reaching 6.3% (56/857) after 2010, and it was largely (4.2%) adopted in early preterm infants. The proportion of vaginal deliveries in women with undetectable viral load (VL) increased over time and was 9.9% (85/857) in 2011-2016; no infection occurred among them. In children followed up since birth MTCT, rate was 3.5% (96/2783) in 1996-2003; 1.4% (36/2480) in 2004-2010; and 1.1% (9/835) in 2011-2016. At a multivariate analysis, factors associated with MTCT were vaginal delivery with detectable or missing VL or nonelective caesarean delivery, prematurity, breastfeeding, lack of maternal or neonatal antiretroviral therapy, detectable maternal VL, and age at first observation. Previously described increased risk of offspring of immigrant women was not confirmed.

Conclusions Risk of MTCT in Italy is ongoing, even in recent years, underling the need for implementation of the current screening program in pregnancy. Large combination neonatal prophylaxis use in preterm infants was observed, even if data on safety and efficacy in prematures are poor.

12

Apr, 2018

ODYSSEY B has completed recruitment with 395 children enrolled

 

ODYSSEY B, which compares dolutegravir versus standard-of-care drugs in HIV-infected children who are starting second-line treatment, has completed recruitment ahead of target. 395 children have enrolled, mostly in Africa. Enrolment into ODYSSEY A for children starting treatment for the first time continues.

In addition a pharmacokinetic (PK) substudy within ODYSSEY has been completed which will help to define simple dosing of dolutegravir in African children; data will be shared with WHO and is being requested by the FDA. Further PK work is planned.

A big thanks to all members of the ODYSSEY team (current and past) and participating sites in Germany, Portugal, South Africa, Spain, Thailand, Uganda, UK and Zimbabwe.

 


ODYSSEY is a multi-centre, randomised clinical trial to assess the efficacy and toxicity of Dolutegravir plus 2 NRTI versus standard of care among HIV positive children and adolescents. PENTA is sponsor of this study, with 700 patients to be enrolled in 30 sites in Europe, the US, Latin America, Africa and Asia.

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