CROI 2020 Abstract eBook

Abstract eBook

Poster Abstracts

808 SEROSTATUS IS A MARKER FOR SUSTAINED VIRAL SUPPRESSION IN EARLY TREATED CHILDREN Gbolahan Ajibola 1 , Pilar Garcia Broncano 2 , Kenneth Maswabi 1 , Kara Bennett 3 , Michael D. Hughes 4 , Sikhulile Moyo 1 , Terence Mohammed 1 , Patrick Jean- Philippe 5 , Maureen Sakoi-Mosetlhi 1 , Oganne Batlang 1 , Shahin Lockman 4 , Joseph Makhema 1 , Daniel R. Kuritzkes 6 , Mathias Lichterfeld 6 , Roger L. Shapiro 4 1 Botswana Harvard AIDS Institute Partnership, Gabarone, Botswana, 2 Ragon Institute of MGH, MIT and Harvard, Cambridge, MA, USA, 3 Bennett Statistical Consulting, Inc, New York, NY, USA, 4 Harvard T.H. Chan School of Public Health, Boston, MA, USA, 5 NIH, Bethesda, MD, USA, 6 Brigham and Women's Hospital, Boston, MA, USA Background: Markers for sustained viral suppression over time are not available for HIV infection. We evaluated whether HIV serology was a useful marker for sustained RNA suppression or low cell-associated HIV reservoir among HIV-infected children treated very early in life. Methods: The Early Infant Treatment Study (EIT) started antiretroviral treatment (ART) for HIV-infected children at < 7 days of age. Quantitative HIV DNA was evaluated every 1-3 months in PBMCs, and at 84 weeks with repeat qualitative whole blood DNA PCR testing and dual enzyme immunosorbent assay (EIA). Children starting ART at age 30-365 days in the Botswana ART program and sampled at 24-36 months of age served as controls. Comparisons were by Wilcoxon Rank Sum testing. Results: Of 40 HIV+ children enrolled in EIT, 30 had reached 84 weeks by the time of this analysis; 14 (47%) had sustained RNA < 40 copies/mL at all visits from 24 to 84 weeks, including 12 (86%) with negative EIA at week 84, and 2 (14%) with indeterminate EIA. Among the 16 with > 40 copies/mL at one or more visits from 24 to 84 weeks, 5 (31%) had negative EIA, 10 (63%) had positive EIA, and 1 (6%) were indeterminate (Table). For a threshold of 40 copies/mL, the negative predictive value of the EIA was 71% (12/17) for sustained viral suppression from 24 to 84 weeks, and the positive predictive value was 100% (10/10) for lack of sustained suppression. For a threshold of 400 copies/mL, the negative predictive value was 100% (17/17), and the positive predictive value was 90% (9/10). Whole blood qualitative HIV DNA PCR at 84 weeks was negative for 14 (47%) children, positive for 15 (50%), and indeterminate for 1 (3%), and the DNA result was concordant with EIA testing for 73% (19/26) with interpretable results for both tests (Table). Among the first 17 EIT children with quantitative cell-associated DNA testing available at 84 weeks, the median DNA reservoir was significantly lower than among 10 control children (10.9 vs. 981.4 copies/million cells; p=<0.001). However, unlike plasma RNA, cell-associated DNA was not associated with the EIA test result at 84 weeks (p=0.63) in this first group of EIT children tested. Conclusion: HIV serostatus at 84 weeks was a marker for sustained RNA suppression among HIV-infected children treated from the first week of life, and may be useful in longitudinal follow-up. Very low viral reservoirs continue to be noted among early-treated children.

(ART). We studied NK cells phenotype and function in perinatally HIV-infected children (PHIV) enrolled in a multicenter cross-sectional study (CARMA, EPIICAL consortium), who started ART at different ages (early treated, ET ≤ 6 months; late treated, LT > 6 months to 2 years). Methods: 40 PHIV who started ART< 2 years of life and had undetectable viremia (< 50 HIV copies/ml) for at least 5 years, were enrolled in 7 European research centers. HIV-1 DNA copies/10 6 PBMCs were measured by real-time PCR. NK cells were analyzed by flow cytometry for % of CD56high, CD56dim, CD56neg subsets, receptor expression, maturation profile, degranulation capacity (CD107a expression) in the presence or not of K562 cells, and IFNγ production after stimulation or not with cytokines. Data were analyzed by Spearman correlation plots and multivariable Poisson regression model (adjusted for baseline %CD4 and RNA HIV viral load and for age at ART start as interaction term, either ET or LT) to explore the association between NK cell parameters and HIV reservoir modulated by age at ART start. Results: Later treatment in PHIV leads to a shift of NK cells to the anergic CD56neg subset that is associated with an increase of HIV reservoir size. For each 1% increase in %CD56neg, 3% upregulation of HIV reservoir is found and this effect is reduced in ET. LT display a persistent “activated” phenotype (i.e. NKp46+, NKG2D+, high Perforin expression) that is not present in ET: for each 1-unit increase in % of NKG2D+, % of NKp46+ or Perforin mean fluorescence intensity, there is an enrichment of 1%, 4% or 0,01% in HIV reservoir, respectively. Moreover, %CD107a+ and %IFNγ+ non-stimulated NK cells show a positive association with HIV DNA, but these effects are decreased in ET. Finally, among CD56dim cells, the frequencies of early differentiated and mature cells are associated with HIV DNA in a positive and inverse manner, respectively, whereas these effects were lower in ET. Conclusion: Our results demonstrate that starting ART as soon as possible after birth in PHIV preserves NK cell features. Notably, we show for the first time that an intact NK cell compartment in PHIV is associated with lower HIV viral reservoir.

Poster Abstracts

810 MARKERS OF HIV RESERVOIR SIZE IN INFECTED CHILDREN ON LONG- TERM VIRAL CONTROL Stefano Rinaldi 1 , Suresh Pallikkuth 1 , Lesley R. De Armas 1 , Rajendra Pahwa 1 , Nicola Cotugno 2 , Pablo Rojo Conejo 3 , Eleni Nastouli 4 , Kathleen Gärtner 4 , Nigel Klein 4 , Caroline Foster 5 , Anita De Rossi 6 , Carlo Giaquinto 6 , Paolo Rossi 2 , Paolo Palma 2 , Savita Pahwa 1 1 University of Miami, Miami, FL, USA, 2 Bambino Gesu Children's Hospital, Rome, Italy, 3 Hospital Universitario 12 de Octubre, Madrid, Spain, 4 UCL Great Ormond Street Institute of Child Health, London, UK, 5 Imperial College Healthcare NHS Trust, London, UK, 6 University of Padova, Padova, Italy Background: Curative strategies for HIV will need to eliminate the replication competent latent reservoir. Immune Checkpoint molecules (ICP) are promising therapeutic targets for the elimination of the HIV latent reservoir, as CD4 T cells expressing ICP have been shown to preferentially harbor latent, replication- competent HIV. T cells expressing ICP are also considered as being exhausted. T follicular helper cell subset of CD4 T cells are critical for B cell differentiation for which induction of IL-21 is favorable while IL-2 is inhibitory. Here a cohort of HIV vertically infected children and young adults under durable viral control (PHIV) were investigated for CD4 ICP, immune activation (IA) markers and function in relation to HIV reservoir size.

809 NK CELLS ARE PRESERVED BY EARLY ART IN HIV-INFECTED CHILDREN WITH LOWER RESERVOIR Sonia Zicari 1 , Margherita Doria 1 , Sara Dominguez Rodriguez 2 , Nicola Cotugno 1 , Alfredo Tagarro 2 , Pablo Rojo Conejo 2 , Eleni Nastouli 3 , Kathleen Gartner 3 , Nigel Klein 4 , Caroline Foster 5 , Savita Pahwa 6 , Anita De Rossi 7 , Carlo Giaquinto 7 , Paolo Rossi 1 , Paolo Palma 1 , for the EPIICAL Consortium 1 Bambino Gesu Children's Hospital, Rome, Italy, 2 Hospital Universitario 12 de Octubre, Madrid, Spain, 3 Great Ormond Street NHS Foundation Trust, London, UK, 4 London School of Hygiene & Tropical Medicine, London, UK, 5 Imperial College Healthcare NHS Trust, London, UK, 6 University of Miami, Miami, FL, USA, 7 University of Padova, Padova, Italy Background: HIV infection causes pathologic changes in the natural killer (NK) cell compartment that can be only partially restored by antiretroviral therapy

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