CROI 2019 Abstract eBook

Abstract eBook

Poster Abstracts

have a role controlling HIV during chronic infection. Furthermore, we showed that Tfh1 express higher CCR5 levels compared to other TFh populations. CCR5 expressing Tfh1 are increased in treated individuals suggesting preferential infection on this subset. Our results encourage further Tfh1 studies to detail their role on HIV control and persistence

aminoacid valine, could not only be used as biomarkers for a rapid screening of future loss of virological control but also can be suggested as therapeutic targets in EC.

268 KSHV-ASSOCIATED MORTALITY IN HIV-INFECTED SOUTH AFRICANS WITH SUSPECTED TUBERCULOSIS Melissa J. Blumenthal 1 , Charlotte Schutz 1 , David Barr 2 , Vickie Marshall 3 , Denise Whitby 3 , Arieh Katz 1 , Thomas S. Uldrick 4 , Graeme Meintjes 1 , Georgia Schäfer 1 1 University of Cape Town, Cape Town, South Africa, 2 University of Liverpool, Liverpool, UK, 3 Frederick National Laboratory for Cancer Research, Frederick, MD, USA, 4 Fred Hutchinson Cancer Research Center, Seattle, WA, USA Background: Despite increasing numbers of HIV-infected South Africans receiving antiretroviral therapy, tuberculosis remains the leading cause of mortality. Approximately 25% of suspected tuberculosis is not confirmed microbiologically. We assessed whether co-infection with Kaposi Sarcoma- associated Herpes Virus (KSHV), and particularly the newly described KSHV inflammatory cytokine syndrome (KICS) contributes to mortality in HIV-infected patients with suspected tuberculosis. Methods: We conducted a cohort study of HIV-infected patients presenting to Khayelitsha Hospital, Cape Town, South Africa, with suspected tuberculosis and followed for 12 weeks. KSHV serostatus was evaluated using ELISA for KSHV K8.1 and LANA. KSHV DNA was measured in blood cells. Clinical correlatives of KSHV lytic activation were evaluated. KSHV viral load and clinical criteria for KICS were evaluated for prognostic value. Results: 682 participants were accrued, 47%men, 53%women. Median age 36 years (range: 18-80), median CD4 count 62 cells/μl (range: 0-526). 30.7% (95% CI: 27-34%) were KSHV seropositive. 10 (1.5%) had clinical Kaposi sarcoma, 5% had elevated cell-associated KSHV DNA (>100 copies/10 6 cells). Anemia was associated with antibodies against KSHV lytic antigen K8.1 (p=0.003). Overall, 22% died. In patients without tuberculosis or other microbiologically confirmed co-infections, elevated KSHV viral load was associated with mortality after adjusting for age, sex, CD4 count and ART (p=0.023, OR=6.467 [95% CI: 1.290, 32.406]). Applying KICS working case criteria, we identified six «possible KICS» patients. Five died, a significantly worse survival (p<0.0001) than other patients without microbiologically confirmed co-infections. Conclusion: Due to high mortality associated with KICS, contribution of lytically active KSHV in critically ill patients presenting with tuberculosis should be considered to avoid misdiagnosis and to determine appropriate treatment strategies. KSHV viral load testing and application of KICS criteria is warranted to identify HIV-infected South African patients with suspected tuberculosis but no microbiologically identified infection at high risk of death.

267 METABOLOMIC PROFILE ASSOCIATED WITH LOSS OF SPONTANEOUS HIV-1 ELITE CONTROL Esther Rodríguez-Gallego 1 , Laura Tarancon-Diez 2 , Verónica Alba 1 , Anna Rull 1 , Joaquim Peraire 1 , Consuelo Viladés 1 , Agathe León 3 , Norma Rallón 4 , Carmen Rodriguez 5 , Cecilio Lopez-Galindez 6 , Maria Pernas 6 , Manuel Leal 2 , Francesc Vidal 1 , Ezequiel Ruiz-Mateos 2 , for the ECRIS integrated in the Spanish AIDS Research Network 1 Hospital Universitario de Tarragona Joan XXIII, Tarragona, Spain, 2 Institute of Biomedicine of Seville, Sevilla, Spain, 3 Hospital Clinic of Barcelona, Barcelona, Spain, 4 Fundacion Jimenez Diaz, Madrid, Spain, 5 Centro Sandoval, Madrid, Spain, 6 Institute de Salud Carlos III, Majadahonda, Spain Background: Although Elite Controllers (EC) spontaneously control HIV-1 replication without antiretroviral therapy, approximately 25% of them lose virological control over time. Recently, it has been demonstrated that immunolovirological factors characterized the loss of spontaneous control. To date, no longitudinal study elucidating the metabolomic profile associated with the loss of spontaneous HIV-1 elite control has been performed. In this sense, the aim of this work was to perform a metabolomic approach to identify the underlying mechanistic pathways and potential predictive biomarkers associated with the virological loss of control. Methods: Plasma samples from EC who spontaneously lost virological control (Transient Controllers,TC, n=8), at two and one year before the loss of control, were compared with a control group of EC who persistently maintained virological control during the same follow-up period (Persistent Controllers, PC, n=8), up to two determinations were performed at one-year interval. The determination of metabolites and plasma lipids was performed by GC-qTOF and LC-qTOF using targeted and untargeted approaches. Metabolite levels were associated with the polifunctionality of HIV-specific CD8-T cell response. A multivariate analysis was performed in order to select and evaluate the performance of the potential biomarkers. Results: We were able to identify and quantify a total of 70 metabolites and 334 lipids in plasma samples. Before the loss of control, TC showed a metabolomic profile characterized by alterations in glycolysis, Krebs cycle, branched amino acid catabolism and lipid metabolism. Besides, CD8+ T-cell polyfunctionality from PC and TC before the loss of control was strongly associated with these metabolites and lipid levels (p<0.05 and r>±0.6). Finally, the aminoacid valine showed the highest discriminatory power between TC and PC (100% of sensitivity and specificity). Conclusion: Our study determined a specific metabolomic profile associated with the spontaneous loss of virological control in EC. This profile was characterized by higher immunological activation, oxidative stress and mitochondrial dysfunction. Metabolites and lipid plasma levels were strongly correlated with immunological parameters. These key metabolites, mainly the

Poster Abstracts

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CROI 2019