CROI 2017 Abstract e-Book

Abstract eBook

Poster and Themed Discussion Abstracts

Conclusion: Neonatal MPs may be important in the pathogenesis of pediatric AIDS and serve as a target to offset HAND in children. Current pediatric cART regimens may not be sufficient, therefore, novel therapeutics need to be developed. 830 CENTRAL NERVOUS SYSTEM PENETRATION OF ANTIRETROVIRAL THERAPY IN HIV-INFECTED CHILDREN Malon V. Hof 1 , Charlotte Blokhuis 2 , Sophie Cohen 2 , Henriëtte J. Scherpbier 2 , Ferdinand Wit 3 , Marcel Pistorius 1 , Neeltje A. Kootstra 1 , Charlotte E. Teunissen 4 , Ron Mathot 1 , Dasja Pajkrt 2 1 Academic Med Cntr, Amsterdam, Netherlands, 2 Emma Children’s Hosp/Academic Med Cntr, Amsterdam, Netherlands, 3 Stichting HIV Monitoring and Academic Med Cntr, Amsterdam, Netherlands, 4 VU Univ Med Cntr, Amsterdam, Netherlands Background: Despite optimal responses to combination antiretroviral therapy (cART), HIV-infected children continue to show neurocognitive deficits with macro- and microstructural brain injury and signs of neuroinflammation. Subtherapeutic central nervous system (CNS) drug levels may contribute to neuropathology in these children. Also, chronic HIV infection has been associated with blood-brain barrier (BBB) breakdown. Pediatric data on cerebrospinal fluid (CSF) cART penetration is scarce. We evaluated cART levels in CSF and plasma and assessed whether CSF drug penetration is related to BBB function, intrathecal inflammation and immune activation in HIV-infected children on suppressive cART. Methods: This cross-sectional study included perinatally HIV-infected children between 8-18 years old from the Academic Medical Center, Amsterdam. CSF was collected from a subset of patients stable on cART in whom a lumbar puncture was indicated as part of routine patient care. CSF and plasma total drug levels were measured and CSF penetration was assessed using each drug’s CSF-to-plasma concentration ratio. BBB permeability was defined as the albumin CSF-to-plasma ratio. Intrathecal inflammation/immune activation markers included CRP, IL-6, soluble CD14 and soluble CD163. Potential associations were explored using Spearman’s rank correlation. Results: Of the 36 perinatally HIV-infected children included, paired CSF and serum samples were available from 20 cART-treated children. All participants were virologically suppressed in blood and CSF. The median CSF penetration of lopinavir (0.12%), efavirenz (0.36%) and tenofovir (1.95%) was poor compared to lamivudine (34%), emtricitabine (35%), nevirapine (48%), zidovudine (52%) and abacavir (56%) (Figure 1). CSF penetration of lamivudine, abacavir, efavirenz and lopinavir was not associated with age or BBB permeability. There was no correlation between CSF penetration of these antiretrovirals and inflammation/immune activation markers soluble CD14, soluble CD163, CRP and IL6 in CSF. Conclusion: Similar to adult patients, CSF penetration of lopinavir, efavirenz and tenofovir is poor in pediatric HIV. We found no associations between CSF penetration of cART and BBB permeability or inflammatory markers in CSF. This suggests cART-specific properties may be more important in CSF penetration than the studied host related factors. Alternatively, HIV related neuroinflammation in children might be at such a low grade, that BBB permeability remains unaltered.

Poster and Themed Discussion Abstracts

831 CURRENT TRENDS IN CHILDREN WITH HIV DIAGNOSED IN THE UK AND IRELAND Helen Peters , Kate Francis, Intira J. Collins, Ali Judd, Claire Thorne Univ Coll London, London, UK Background: Incidence of mother-to-child HIV transmission has declined to <0.5% among diagnosed HIV+ pregnant women delivering in the UK/Ireland (UK/I), however most children living with HIV in UK/I were born abroad. We describe evolving trends in the characteristics of children at diagnosis in the UK/I from 2000-15. Methods: All children (<16y) diagnosed with HIV are reported to the National Study of HIV in Pregnancy and Childhood through an active surveillance system, including infants and children born in the UK/I to diagnosed and undiagnosed mothers, plus children born abroad arriving in the UK/I with unknown or known HIV status. HIV status is reconfirmed after arrival in the latter. Children receiving paediatric HIV care in UK/I are followed in the Collaborative HIV Paediatric Study (CHIPS). We report characteristics at time of UK/I diagnosis among those diagnosed in 2000-15. Results: Overall 1,528 children were diagnosed, annual numbers peaking at 150 during 2003-4 and stabilising at 30-50 per year since 2012 (p<0.001). 53% (804/1517) were female, 97% (1369/1408) reported as vertically infected and 65% (999/1528) born abroad (mainly sub-Saharan Africa), with this proportion increasing to 73% (109/150) from 2012. Among UK/I-born children born <2005, median age at diagnosis was 9mth (IQR 3mth-3y) vs 3mth (0.5y-1y) for those born ≥2010; among children born abroad median ages were 6yr (3-9y) vs 3yr (2-3y) respectively. The proportion of children with CDC C or B symptoms at UK/I diagnosis declined from 26% (132/509) and 34% (171/509) of those diagnosed in 2000-3, to 2% (3/150) and 11% (17/150) since 2012 respectively (p<0.001, for both trends). Of children born abroad 23% (228/999) were diagnosed before entering the UK/I, increasing over time (8% in 2000-3 to 55%≥2012, p<0.001). By arrival 49% (112/228) were ART experienced [Figure], median age at ART start was 6y (IQR: 2y, 9y). Of 88/112 with known regimen, 76% initiated on a NNRTI and 14% a boosted-PI based regimen. Of patients linked in CHIPS with ART data after entry (73/88), 23% switched to a new regimen (change across drug/within PI class) within 1 year of arrival in UK/I. Conclusion: Annual numbers of newly diagnosed children in the UK/I continue to decline, with increasing proportions of children born abroad and treatment experienced at arrival. Median age at diagnosis has decreased significantly, although remains higher for children born abroad. An encouraging trend is the declining proportion presenting with CDC B/C symptoms.

CROI 2017 359