CROI 2016 Abstract eBook

Abstract Listing

Poster Abstracts

835 Clinical Outcomes in Adults With Perinatal HIV After Transfer From Pediatric Care Rebecca L. Hope 1 ; Ali Judd 2 ; Caroline Foster 3 ; Katia Prime 4 ; PatTookey 5 ; Eva Jungmann 6 ; RussellViner 5 1 IDEO.org, Oakland, CA, USA; 2 Med Rsr Council Clinical Trials Unit at Univ Coll London, London, UK; 3 Imperial Coll Hlthcare NHS Trust, London, UK; 4 St George’s & Queen Mary’s Hosp, London, UK; 5 Univ Coll London, London, UK; 6 Mortimer Market Cntr, London, UK Background: With improved survival, increasing numbers of adolescents with perinatal HIV (PaHIV) are transitioning from pediatric to adult care, but there are few published data on clinical outcomes in adult care. This longitudinal retrospective cohort study investigated retention in care, mortality and clinical outcomes in young PaHIV adults after transfer to 4 large adult HIV clinics in London, UK. Methods: Adult care data for 211 PaHIV adults at the 4 hospitals (collected 2011-2013) were combined with their pediatric data from the Collaborative HIV Paediatric Study (CHIPS). Mean CD4 and the proportion with viral load <50c/mL were compared pre- and post-transfer. Linear and logistic regression models with random effects investigated the effect of clinical, demographic and socioeconomic factors on CD4 trajectories, viral load, and non-attendance (not seen ≥12 months) and/or death, in the post-transfer period. Results: Median age at last follow-up was 21.9yrs [IQR 19.8,23.6] and median duration of follow-up was 15 years [11,18]. Most (89.6%) were on antiretrovirals. Median age at transfer was 17.6yrs [16.6,18.4] and median follow-up post-transfer was 3yrs [1.4,5.0]. Half (56%) attended ≥1 pediatric and adult transition clinics during transfer and 43% switched hospitals for adult care. Transfer was associated with increased virological suppression from 43% at 12 months pre-transfer to 44% at transfer and 63% at last visit (n=211, χ 2 trend p<0.001). Although mean CD4 decreased from 450c/mm3 in the 2 years pre-transfer to 420 in the 2 years post-transfer (p<0.001), the rate of decline slowed after transfer (from 28.3c/mm3/year to 22.8c/mm3/year post-transfer, p<0.001, Figure). Older current age (β=26.2) and non-progression during childhood (β=246.5) were multivariate predictors of higher CD4 in adult care, and male sex (β =-81.0) and virological failure at transfer (β =-286.2) predictors of lower CD4 (all p<0.05). Those who switched hospital for adult care had higher odds of non-attendance (26/211) and/or death (9/211) (aOR=5.3, 95%CI 2.0, 13.7). Conclusions: Viral suppression in PaHIV patients in 4 adult HIV clinics in London improved after transfer from pediatrics. Although mean CD4 decreased after transfer, the decline in immune function was steeper in the 2 years pre-transfer, suggesting a critical time for adherence interventions during transition preparation. Staying at the same hospital had a positive effect on attendance/survival in adult care, suggesting the importance of continuity of care.

836 Strong IFN-g Responses and Limited HIV Reservoirs in Adolescent Virologic Controllers

Jason Brophy 1 ; Fatima Kakkar 2 ; Hinatea Dieumegard 3 ; Amelie Pagliuzza 4 ; Ari Bitnun 5 ; Lindy Samson 1 ; Stanley Read 5 ; Nicolas Chomont 6 ; Hugo Soudeyns 7 ; for the EPIC4 Study Group 1 Children’s Hosp of Eastern Ontario, Ottawa, ON, Canada; 2 Univ de Montréal, Montréal, QC, Canada; 3 CHU Sainte-Justine, Montréal, QC, Canada; 4 CRCHUM, Montreal, QC, Canada; 5 Hosp for Sick Children, Univ of Toronto, Toronto, ON, Canada; 6 Univ de Montréal, Montreal, QC, Canada; 7 CHU Sainte-Justine, Montreal, QC, Canada Background: Insights from the “Mississippi baby” and Visconti cohort have shed light on the benefits of early ART after primary HIV infection to limit reservoir size. We describe two cases of pre- and post-treatment control in perinatally HIV-1-infected youth. Methods: Routine virologic and immunologic parameters were monitored since diagnosis. Study investigations included: HIV reservoir assessments (TILDA and qRT-PCR for total and integrated DNA); cell-mediated immune responses (CMI); and HLA typing. CMI were assessed using pooled clade-matched HIV-1 Gag peptide panels in matrix format and IFN-g ELISpot and expressed as spot-forming units (SFU) per 10 6 PBMC. Results: Case 1, diagnosed at age 10 years, had an initial viral load (VL) of <50 c/mL, but was positive for HIV DNA (clade C). Subsequently, she had only 2 detectable VLs of 71 and 57 c/mL at age 12 and 17 years respectively, with the remainder below detection. Now 17 years, her CD4 counts have been normal throughout. Case 2 was diagnosed at age 11 months, at which time VL was 128,400 c/mL (clade D); nadir CD4 count was 1170 cells/mL (18%). She received dual ARV therapy until age 3 years without virologic suppression, followed by 3-drug cART which led to suppression. Treatment was interrupted at age 12 years with ongoing suppression (<50 c/mL) for 5 years. Now 18 years, over the past year VLs have been consistently detectable up to 300 c/mL, with intermittent adherence to cART initiated for a single CD4 count of 326 cells/mL. TILDA in both cases showed low positivity at 1.5 cells/10 6 CD4+ T cells. Total and integrated HIV DNA measurements were 479 and 102 copies/10 6 CD4+ T cells for Case 1 and 1076 and 564 for Case 2. Both subjects exhibited strong IFN-g responses (Case 1: 97-7032, Case 2: 0-5103 SFU/10 6 PBMC) and breadth of antigen recognition (22/22 and 13/14 peptide pools recognized, respectively). These CMI are in the top quartile compared to chronically infected children and adults. Case 1 possessed no HLA genotypes predictive of elite control; Case 2 possessed one HLA-B*81 haplotype. Conclusions: In contrast to the recently reported French adolescent post-treatment controller who had weak CMI, these youth (one an elite controller, the other a post-treatment controller) demonstrated HIV-specific CMI that are substantively larger and broader than those observed in pediatric or adult patients with viral suppression on cART. These results underscore the potential impact of enhanced CMI in virologic remission in perinatally infected youth. 837 Kinetics of Cell-Associated HIV DNA During Viral Suppression in HIV-Infected Children Matias Moragas ; Debora Mecikovsky; Solange Arazi Caillaud; Paula Aulicino; Rosa Bologna; Luisa Sen; Andrea Mangano Hosp de Pediatría SAMIC Prof Dr Juan P. Garrahan, Buenos Aires, Argentina Background: Although the success of combined antiretroviral therapy (cART) to control viral replication, HIV erradication has not been yet achieved. One of the major known obstacles is the establishment of viral reservoirs very early after infection. The aim of this study was to determine the decay in the level of cell-associated HIV-DNA (CA-HIV-DNA) in children with sustained virological suppression (VS) for many years on cART. Methods: The research was conducted in an academic pediatric hospital including 37 HIV-infected children by vertical transmission with more than 2 years on VS, defined as plasma viral load below the limit of detection of the available assay. CA-HIV-DNA levels were quantified by a semi-nested real time PCR with Taqman probes targetting LTR-gag region in PBMCs. Samples were tested at pre-cART, at 2 and 4 years (± 6 months) on VS. Clinical, virological and inmunological data were collected. Mann-Whitney test and with Pearson´s or Sperman correlation coefficient were used for data analysis.

Poster Abstracts

350

CROI 2016