CROI 2017 Abstract e-Book

Abstract eBook

Poster and Themed Discussion Abstracts

phylogenetic trees. Drug resistance mutations were not detected in DSC shedding pol specimens. Due to the unexpectedly low yield of SGA sequences, the 13 CVL that tested positive for RNA were retested by Abbott and only 2/13 (15%) specimens tested positive. Conclusion: Intermittent DSC HIV RNA shedding from the GT when HIV replication was suppressed in plasma was detected infrequently. In cases where DSC shedding was phylogenetically characterized we found primarily monotypic RNA and DNA sequences from subjects known to have diverse HIV quasispecies prior to ART, which suggests DSC shedding may come from clones of cells that produce virions. None of our findings suggested ongoing HIV replication in the genital tract, but rather suggest that inflammatory signals may have induced cell to produced virions. 225 PREDICTORS OF IMMUNE RECOVERY AFTER ART IN VERY ADVANCED DISEASE Pablo F. Belaunzaran-Zamudio 1 , Alejandro Olmedo 1 , Irini Sereti 2 , Yanink Caro-Vega 1 , Adam Rupert 3 , Alondra López 1 , Ian Sanne 4 , Juan Sierra-Madero 1 , Michael M. Lederman 5 1 Instituto Nacional de Ciencias Medicas y Nutrición Salvador Zuirán, Mexico, Mexico, 2 NIAID, Bethesda, MD, USA, 3 Leidos Biomed Rsr, Inc, Frederick, VA, USA, 4 Univ of the Witwatersrand, Johannesburg, South Africa, 5 Case Western Reserve Univ, Cleveland, OH, USA Background: In the CADIRIS trial ART naïve patients with CD4 <100/uL were studied to examine the effect of CCR5 antagonism on occurrence of IRIS. In this analysis we aimed to identify baseline biomarkers as predictors of immune recovery (IR). Methods: We measured plasma levels of interferon-γ, interleukin (IL)-1b, IL-6, IL-8, IL-10, IL-12p70, IL-17, tumor necrosis factor-α (TNFα), C-Reactive Protein (CRP), serum amyloid A (SAA), P-selectin, interferon-inducible protein (IP)-10, Leukotriene B4 (LTB4), soluble (s) CD14, sCD40 ligand, sCD163, Von Willebrand Factor (vWF), fibrinogen, proteins C and S, D-Dimer, and hydroxyvitamin D before ART initiation. Immune recovery (IR) was defined as reaching CD4>200cell/uL during 48-week follow-up after ART initiation. Results: We studied 267 Mexican and South African patients enrolled in the CADIRIS trial (133 received placebo and 134 maraviroc). One hundred and twenty-nine subjects (48%) had a CD4 measurement >200cells/uL during follow-up (48 weeks). The distribution of patients with immune recovery was not different between treatment arms (placebo 58 (44%) and maraviroc 71 (53%), p=0.1). Lower levels of CRP (OR 9.8 per mg/l, p=0.01), SAA (OR 0.99 per mg/L, p=0.04), IL-8 (OR 0.97, p=0.04), and sCD163 (OR 0.99 per ng/mL, p=0.03) were associated with increasing odds of reaching a CD4 count ≥200 cells/µL during follow-up. In multivariate analyses, including age, baseline HIV-RNA, CD4, CRP, IL-8 and IL-17 and sCD163 in a logistic model we observed significant, inverse relationships between increasing age (OR 0.96 95%CI 0.94-0.99 per increasing year, p=0.04), baseline CRP (OR 0.98 95%CI 097-0.99 for every mg/dL increase, p=0.04) and sCD163 levels (OR 0.98 95%CI 099-0.99 for every ng/mL increase, p=0.04) the likelihood of adequate immune recovery. Conclusion: In chronically HIV-infected patients initiating ART in advanced disease, increasing age, high CRP and sCD163 levels were inversely associated with the probability of achieving adequate immune recovery during the first year after ART initiation 226 PARADOXICAL CD4 DECLINE ON ART: A NOVEL, RARE AND PERPLEXING IMMUNOLOGIC OUTCOME Andrea Lisco 1 , Itzchak Levy 2 , Jason Brophy 3 , Claire Deleage 4 , Chun-Shu Wong 1 , Adam Rupert 5 , Caryn G. Morse 6 , Shanna Chan 7 , Jacob D. Estes 4 , Irini Sereti 1 1 NIAID, Bethesda, MD, USA, 2 Academic Med Cntr Hosp, Tel Aviv, Israel, 3 Children’s Hosp of Eastern Ontario, Ottawa, Canada, 4 Frederick Natl Lab for Cancer Rsr, Frederick, USA, 5 Leidos Biomed Rsr, Inc., Frederick, MD, USA, 6 NIH, Bethesda, MD, USA, 7 Winnipeg Regional Hlth Authority, Manitoba, Canada Background: The goal of antiretroviral therapy (ARV) is to suppress HIV-1 replication and restore CD4 T cells. Immune activation, lymphoid tissue fibrosis and impaired homeostatic signaling have been associated with poor CD4 recovery. Here, we report on HIV-infected individuals, who had a paradoxical decline in CD4 despite ARV-mediated plasma HIV suppression. We defined such immunological outcome as extreme immune decline (EXID). Methods: Demographic, clinical and virological characteristics were analyzed for EXID subjects (n=5), and compared to immunological responders (IR, defined as CD4 > 270 cells/μL after 2 years on ARV, n=15) and immunological non-responders (INR, defined as CD4 < 270 cells/μL after 2 years on ARV, n=8). PBMCs were immunophenotyped by flow cytometry. Plasma cytokines and anti-cytokine autoantibodies were measured by ELISA and multiplex-bead array. Continuous variables were compared by Mann–Whitney test. Results: All EXID subjects were infected with a non-B HIV-1 subtype and 4 out of 5 (80%) were African. No subjects were on tenofovir/didanosine-based regimens and 80% of EXID subjects had received ≥3 different ARV regimens. After median ARV duration of 2 years, EXID subjects had a median CD4 decrease of 170 cells/μL, while IR and INR had a median increase of 183 cells/μL and 388 cells/μL, respectively (p=0.02, Figure 1A). The proportion of naïve CD4 cells was different between the EXID, IR and INR (4%, 15%, 33%, respectively, p<0.05). Although, the fraction of HLA-DR/CD38/CD8 T cells was different between IR and INR subjects (29% vs 19%, p=0.01), EXID had a similar proportion of these cells compared to IR or INR subjects (23%, p>0.05). No difference was noted in plasma levels of inflammatory cytokines between EXID and HIV-negative controls (HC), while TNFα, IL-8 and IP-10 were increased in INR compared to HC (p<0.03, Figure 1B). IL-7 was increased in EXID compared to HC (p<0.01), but not in IR or INR compared to HC (p>0.05, Figure1C). Anti-cytokine autoantibodies were absent in plasma of EXID subjects. Genetic screening for primary immunodeficiencies was performed in 2 EXID subjects and was unrevealing. Conclusion: EXID can occur in absence of lymphoproliferative diseases or myelotoxic nucleoside analogues combinations and may be associated with non-B HIV subtype. EXID is a distinct entity from previously described INR, and is not linked to higher immune activation or increased level of inflammatory cytokines but is accompanied by an increase in homeostatic cytokines.

Poster and Themed Discussion Abstracts

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CROI 2017