CROI 2019 Abstract eBook

Abstract eBook

Poster Abstracts

historical controls with similarly calculated T2 of 3.4 days (and from literature about 2-3 days) and pVL rebound to +0.72 log10 > pre-ART at 6 weeks, as in Group 2. Limitations include small numbers, and high variation. Strengths include coherence of a biologically large effect size on pVL rebound dynamics, on kinetics and on time to loss of activity by dosage group, suggesting dose- and exposure-related vedolizumab effects. Deeper biological study in these cases, and further data from greater numbers, doses and duration is needed to validate and confirm activity of vedolizumab in pursuit of pVL suppression after ART. Björn-Erik O. Jensen 1 , Elena Knops 2 , Nadine Lübke 1 , Annemarie Wensing 3 , Javier Martinez-Picado 4 , Rolf Kaiser 2 , Monique Nijhuis 3 , Maria Salgado 4 , Thomas Harrer 5 , Eva Heger 2 , Johanna M. Eberhard 6 , Ilona Hauber 7 , Carsten Münk 1 , Dieter Häussinger 1 , Guido Kobbe 1 1 Heinrich Heine University Hospital, Düsseldorf, Germany, 2 University of Cologne, Cologne, Germany, 3 Utrecht University, Utrecht, Netherlands, 4 IrsiCaixa Institute for AIDS Research, Badalona, Spain, 5 University Hospital Erlangen, Erlangen, Germany, 6 University Hospital Hamburg–Eppendorf, Hamburg, Germany, 7 Heinrich Pette Institute, Hamburg, Germany Background: A 49y-old HIV-infected male patient received unmodified HSCT from a 10/10 CCR5-d32 donor in Feb 2013 because of acute myeloid leukemia (AML) while in 2nd complete remission (CR). At time of HSCT proviral HIV DNA load was 1.45 log10cop/Mio PBMCs. All anticipated antibodies were detected by western blot. HIV coreceptor-usage was predicted R5 (Sanger: FPR 44.5%; NGS: 0.14% X4 at 3.5% FPR, geno2pheno), confirmed by phenotypic testing (TropChase). He had a 2nd relapse of AML in Jun/13 but after 8 courses of 5-azaC and 4 donor lymphocyte infusions CR was achieved. Immunosuppression was stopped in Oct/17. During HSCT the patient remained on ART until Nov/18 with undetectable plasma viral load. Methods: PBMC and tissues were analysed by ddPCR, qPCR and in situ hybridization in several laboratories as well as humoral and T-cell responses. Infectious virus was analysed on CD4+T-cells (qVOA, MVOA). Patient was registered to IciStem as #19. Results: Almost all PBMC samples were negative for proviral HIV-DNA by qPCR/ddPCR at multiple time points. CSF (Jul/14), rectum (Apr/15, Mar/16), ileum (Mar/16) and bone marrow (Aug/15) were negative. Further testing with 0.1 Mio cells from ileum showed in 1/4 replicates one positive droplet with LTR-, but none with gag-primers. There was also a signal in TCM 0.2 Mio cells (ddPCR 1 positive droplet, qPCR neg) and in TEM 0.36 Mio cells (qPCR 5cop/ Mio cells, ddPCR neg) while all other T-cell subsets were negative in ddPCR & qPCR. No HIV-DNA could be detected by PCR in lymph nodes of May/17, but in situ hybridization assays (RNAscope, DNAscope) detected few positive signals. Viral outgrowth assays (qVOA) in Feb/16, Mar/16 and May/16 were negative (23 Mio CD4+T-cells, IUPM<0.031/Mio cells CD4+T-cells). Mouse VOA (Apr/16: Rag2-/-γc-/-, Apr/17: NOD-SCID IL2gR-/-) were also negative. Gp160 was the only remaining band on the blot. Peptide stimulation assays revealed the presence of CCR5-negative HIV-specific CTL recognizing HLA-A2-restricted RT-epitope YV9 and HLA-B7-restricted Gag-p6 epitope YL9. Conclusion: Despite low signals in ultrasensitive assays no virus could be detected in qVOA/mVOA in the Duesseldorf patient. Taking into account the homozygous CCR5-d32 status we consider a viral rebound to be unlikely. An ATI is the only way to find out whether HIV has been eradicated by allogeneic CCR5-d32 HSCT. Therefore ART was stopped in Nov/18 after thorough discussion with the patient. Despite all plasma samples being negative after ATI longer surveillance is essential. 395 TELMISARTAN DECREASES HIV-1 RNA IN LYMPH NODES IN TREATED HIV INFECTION Netanya S. Utay 1 , Jordan E. Lake 1 , Claire Deleage 2 , Douglas W. Kitch 3 , Eunice Yeh 3 , Karin L. Klingman 4 , Michael M. Lederman 5 , Carl Fichtenbaum 6 , Daniel Douek 7 , Judith S. Currier 8 , Jacob D. Estes 2 , for the A5317 Team 394LB ANALYTIC TREATMENT INTERRUPTION (ATI) AFTER ALLOGENEIC CCR5-D32 HSCT FOR AML IN 2013

1 University of Texas at Houston, Houston, TX, USA, 2 Leidos Biomedical Research, Inc, Frederick, MD, USA, 3 Harvard University, Boston, MA, USA, 4 DAIDS, NIAID, Bethesda, MD, USA, 5 Case Western Reserve University, Cleveland, OH, USA, 6 University of Cincinnati, Cincinnati, OH, USA, 7 National Institute of Allergy and Infectious Diseases, Bethesda, MD, USA, 8 University of California Los Angeles, Los Angeles, CA, USA Background: Chronic inflammation in HIV infection can lead to lymph node (LN) fibrosis and limit CD4+ T-cell recovery. Telmisartan, an angiotensin receptor blocker and PPAR-γ agonist, is anti-inflammatory and anti-fibrotic. We previously reported telmisartan did not decrease LN fibrosis (i.e. collagen I by immunohistochemistry (IHC)) more than ART alone. We hypothesized telmisartan would decrease macrophage infiltration and HIV-1 RNA+ cells and increase CD4+ T-cells in LN. Methods: In this completed, randomized-controlled trial, adults with HIV-1 RNA <50 copies/mL on ART for ≥48 weeks received telmisartan plus ART for 48 weeks or ART alone. The number of LN HIV-1 RNA+ (vRNA+) cells was measured by RNAscope and % CD4+ T cells and CD68+CD163+macrophages by IHC at weeks 0 and 48. Statistical testing used two-sided rank-sum, signed-rank tests and Spearman correlations (α=0.05). Results: Of 44 participants, 93%were male, 50%white non-Hispanic, median age 48 years, CD4+ T-cell count 588 cells/mm ... 3 ... . Week 0 median (IQR) number of vRNA+ cells/10 ... 6 ... cells was 106 (67, 130; n=17) in the telmisartan arm and 75 (0, 118; n=13) for ART alone. By morphology, vRNA+ cells were lymphocytes. After 48 weeks, the number of vRNA+ cells/10 ... 6 ... cells changed by -48 (-88, 0; P=0.004) in the telmisartan arm and +18 (-91, 45; P=0.70) with ART alone, with P=0.28 for the between-arm comparison. Median abundance of CD4+ T cells and macrophages in the B cell follicle (BCF) and T cell zone (TCZ) did not change significantly in either arm. With pooled treatment arms at Week 0, having less LN collagen I was associated with more CD4+ T cells in TCZ (r=-0.47, P=0.004). Having more vRNA+ cells was associated with fewer CD4+ T cells in BCF (r=-0.40, P=0.03) and fewer macrophages in BCF (r=-0.38, P=0.04) and TCZ (r=-0.35, P=0.04). While not associated at Week 0, 48-week increases in CD4+ T cells in TCZ were associated with decreases in macrophages in BCF (r=-0.60, P=0.0009) and TCZ (r=-0.60, P=0.0005) in a pooled analysis. Conclusion: The number of LN HIV-1 RNA+ cells declined 45%with telmisartan added to suppressive ART. At Week 0, people with less LN fibrosis and fewer vRNA+ cells had more LN CD4+ T cells. Decreases in macrophages were accompanied by better LN CD4+ T cell recovery. Further characterization of these macrophages and the reservoir will clarify the interactions between HIV-1, LN immune cells, and their effects on fibrosis and the HIV reservoir.

Poster Abstracts

396 DEPLETION OF BLOOD PD-1+ CD4 T CELLS BY Α-PD-1 ADC SUPPRESSES HIV INFECTION IN VITRO Patricia Jacquier 1 , Craig Fenwick 1 , Song Ding 2 , Giuseppe Pantaleo 1 1 Lausanne University Hospital, Lausanne, Switzerland, 2 EuroVacc Foundation, Amsterdam, Netherlands Background: Despite the efficacy of antiretroviral therapy (ART) at suppressing HIV-1 viral replication, treatment interruption results in viral rebound in the majority of individuals. HIV resurgence is due to the persistence of a long-lived virus reservoir that is not susceptible to ART. Recent studies have shown that PD-1+ CD4 T cells serve as a major cellular reservoir for HIV-1 replication and production, thus providing a strong rationale for developing therapeutic strategies targeting the elimination of PD-1+ CD4 T cells. Methods: An anti-human PD-1 antibody (Ab) was conjugated with an anthracycline toxin to produce an antibody-drug conjugate (ADC) for the

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