CROI 2018 Abstract eBook

Abstract eBook

Poster Abstracts

specific cytokine production by CD8 T cells and the percentage of IgG+ B cells. These data suggest that functional cellular immune responses in HIV infected infants aid in controlling the HIV reservoir size.

864 FACTORS ASSOCIATED WITH HIV DNA LEVELS IN CHILDREN STARTING ART EARLY IN INFANCY Man Chan 1 , Alfredo Tagarro 2 , Paola Zangari 3 , Bridget Ferns 1 , Caroline Foster 4 , Anita De Rossi 5 , Eleni Nastouli 6 , M Ángeles Muñoz-Fernández 7 , Diana Gibb 1 , Paolo Rossi 3 , Carlo Giaquinto 5 , Abdel Babiker 1 , Paolo Palma 3 , Pablo Rojo Conejo 2 1 University College London, London, UK, 2 Hospital Universitario 12 de Octubre, Madrid, Spain, 3 Bambino Gesu Children’s Hospitalital, Rome, Italy, 4 Imperial College Healthcare NHS Trust, London, UK, 5 University of Padova, Padova, Italy, 6 UCL Great Ormond Street Institute of Child Health, London, UK, 7 University Hospital Gregorio Marañon, Madrid, Spain Background: Future strategies aimed at achieving ART-free HIV remission are likely to target individuals with low levels of HIV-1 DNA who started ART early. We investigated factors associated with HIV-1 DNA levels in children starting ART in early infancy. Methods: 51 children with perinatal HIV aged<6 months at start of NNRTI or PI-based ART were included from 5 European sites (1 UK, 2 Spain, 2 Italy). Total HIV-1 DNA was measured in isolated PBMCs 6.3 years (median) after initial viral suppression (≥2 consecutive VL<50), whilst suppressed. Factors associated with log 10 total HIV-1 DNA were analysed using linear regression. Backward elimination was applied to reach the final multivariable model. Results: 55% children were female, 29% had previous AIDS diagnosis (73% diagnosed before or at ART start), 16%were from UK, 31% Spain and 53% Italy. At ART initiation, children were aged median [IQR] 2.3 [1.2,4.1] months, CD4% 37 [24,45]%, CD8% 28 [18,36]%, log 10 VL 5.4 [4.4,5.9] copies/ml. Median age at HIV-1 DNA determination was 7.3 [4.2,10.9] years. Time to viral suppression was 7.98 [4.6,19.3] months and following suppression, 13 (25%) children had suboptimal response [≥2 consecutive VL50-400 followed by VL<50] and/ or experienced periods of viral failure [≥2 consecutive VL≥400 followed by VL<50]. Total HIV-1 DNA was 43 [6,195] copies/10 6 PBMC. In multivariable analysis, lower total HIV-1 DNA was associated with younger age at ART start, higher proportion of time spent virally suppressed and absence of viral failure/ suboptimal response (Table 1). Although there was suggestive evidence for an association with baseline immunological data (CD4, CD4/CD8 ratio and total lymphocyte; P=0.05-0.10) and AIDS diagnosis (P<0.05), these associations failed to reach significance after adjustment. Effect of site remained significant with highest total HIV-1 DNA values in UK and Rome. Sensitivity analyses (excluding 5 children with viral failure or 6 who took ≥3 years to suppress) produced similar results. Conclusion: Our study show that even among children initiating ART<6 months of age, starting ART earlier, spending a higher proportion of time suppressed and absence of viral failure/suboptimal response was linked with lower total HIV-1 DNA. Our findings support early ART start and adherence support in children as a strategy to minimise the size of viral reservoir. Future larger independent studies will be required to confirm results.

Poster Abstracts

863 T AND B CELL RESPONSES ASSOCIATE WITH SMALLER HIV RESERVOIR SIZE IN INFANTS AFTER ART Julie Mitchell 1 , Marta Massanella 2 , Thanyawee Puthanakit 3 , Pope Kosalaraksa 4 , Piyarat Suntarattiwong 5 , Suparat Kanjanavanit 6 , Rawiwan Hansudewechakul 7 , Thitiporn Borkird 8 , Thidarat Jupimai 3 , Panadda Sawangsinth 9 , Mark de Souza 9 , Nicolas Chomont 2 , Jintanat Ananworanich 1 , Lydie Trautmann 1 1 US Military HIV Research Program, Silver Spring, MD, USA, 2 Centre de Research du Centre Hospitalier de l’Université de Montreal, Montreal, QC, Canada, 3 HIV–NAT, Thai Red Cross AIDS Research Centre, Bangkok, Thailand, 4 Khon Kaen University, Khon Kaen, Thailand, 5 Queen Sirikit National Institute of Child Health, Bangkok, Thailand, 6 Nakornping Hospital, Chiang Mai, Thailand, 7 Chiang Rai Prachanukroh Hospital, Chiang Rai, Thailand, 8 Hat Yai Hospital, Songkhla, Thailand, 9 SEARCH, Bangkok, Thailand Background: The infant immune system is characterized by reduced HIV- specific immune responses, resulting in an inability to control HIV viremia. We investigated the activation and maturation of T and B cells in HIV+ infants before and after successful antiretroviral therapy (ART). Methods: Nine HIV-infected Thai infants were included: 4 virally non- suppressed at baseline, either pre-ART (n=2) or on ART 3 weeks (median 4 mo old, range 3-5 mo), and 5 successfully treated for a median of 12 months (range 10-14 mo; median 16 mo old, range 13-19 mo). Comparisons were made with 11 acutely infected Thai adults in RV254 before or after 48 weeks of ART (n=7 and 4, respectively). Integrated HIV DNA levels in CD4 T cells were quantified by ultrasensitive PCR. CD19+CD20+ B cells and CD45RA– CD8 T cells were analyzed by flow cytometry. HIV-specific cytokine production was measured in expanded CD8 T cell lines activated by B-EBV cells pulsed with 74 dominant CRF01_AE HIV peptides. Results: Despite successful viral suppression, frequencies of activated (CD38+HLA-DR+) and proliferating (Ki-67+bcl-2lo) CD8 T cells remained elevated in infants after one year of ART (median 6.3% and 16.2%, respectively), and were higher than those measured in adults after early ART (2.3%, p=0.05; 2.9%, p=0.02, respectively). HIV DNA levels negatively correlated with HIV specific cytokine production after ART, suggesting that CD8 T cell responses are associated with a smaller HIV reservoir size (Panel A). Infants had immature B cell compartments compared to adults at baseline, with high frequencies of IgD+ (98.6% vs 46.2%) and immature transitional B cells (CD27–CD21–CD10+, 9.9%), together with extremely low frequencies of IgG+ B cells (0.3% vs 22.3%). At baseline, the frequency of immature transitional B cells tended to positively correlate with HIV DNA levels (r=1, p=0.08). Infants had HIV DNA levels that negatively correlated with the frequency of IgG+ B cells after one year of ART (r=-0.9, p=0.08, Panel B), suggesting that B cell maturation is also associated with a smaller HIV reservoir size. Conclusion: Elevated frequencies of IgG+ B cells and Ki-67+bcl-2lo CD8 T cells in infants after one year of ART reflect maturation and persistent activation of the immune system. After ART, HIV DNA levels correlated with both the HIV-

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