CROI 2019 Abstract eBook

Abstract eBook

Poster Abstracts

270 PRIMARY ROLE OF KSHV IN PATHOGENESIS OF ENDEMIC AND EPIDEMIC KAPOSI SARCOMA Salum J. Lidenge 1 , For Yue Tso 1 , Andrew V. Kossenkov 2 , Owen Ngalamika 3 , John R. Ngowi 4 , Yasaman Mortazavi 1 , Eun Hee Kwon 1 , Danielle M. Shea 1 , Veenu Minhas 5 , Julius Mwaiselage 4 , Paul M. Lieberman 2 , Charles Wood 1 , John T. West 1 1 University of Nebraska–Lincoln, Lincoln, NE, USA, 2 Wistar Institute, Philadelphia, PA, USA, 3 University Teaching Hospital, Lusaka, Zambia, 4 Ocean Road Cancer Institute, Salaam, Tanzania, 5 University of Nebraska Medical Center, Omaha, NE, USA Background: Kaposi sarcoma (KS)-associated herpesvirus (KSHV) is etiologically linked to all KS forms but mechanisms underlying KS development are unclear. The high incidence of KS in HIV-1+ individuals, epidemic-KS (EpKS), implicates immune dysregulation in co-infection; however, the lack of in-depth comparison with KSHV immune responses in African endemic-KS (EnKS) and the continued incidence of KS despite ART-mediated immune reconstitution make the pathogenetic role of HIV-1 in KS unclear. Methods: We have utilized cohorts of Zambian and Tanzanian KS patients to compare immune responses and expression patterns between EpKS and EnKS patients or asymptomatic controls. Antibody and cytokine responses were investigated in histologically and PCR confirmed EpKS and EnKS patients, versus asymptomatic controls with and without KSHV infection. KSHV-vDNA, total anti-KSHV antibody, KSHV-neutralizing antibody and cytokines were quantified. RNASeq and bioinformatics analyses were used to compare transcriptomes from biopsied KS and normal skin in both KS groups versus asymptomatic controls using DESeq2 algorithm, and FDR<5% results were considered significant. Two- tailed Mann-Whitney U-test was used to assess median differences between groups where P-value <0.05 was considered significant. Results: KSHV was consistently detected in tumors but variably detected in plasma and PBMCs from EpKS and EnKS patients. Consistent with elevated antibody-associated cytokines (IL-6, IL-5 and IL-10), total anti-KSHV and neutralizing antibody titers were higher in EpKS and EnKS patients than in controls (P<0.05). Also, titers of anti-KSHV antibody correlated with neutralizing antibody titers in KS patients (r=0.7384, P<0.0001). Despite HIV-1 co-infection in EpKS, total and neutralizing antibody titers were similar between EpKS and EnKS patients (P=0.3067). Likewise, analyses of transcriptomes from KS tissues with and without HIV-1 co-infection revealed remarkable similarities in gene expression patterns and dysregulated pathways. Conclusion: The detection of similar antibody and cytokine responses as well as transcriptomes in EpKS and EnKS patients suggest that KS results not due to co-infections like HIV-1, but rather primarily due to KSHV-induced pathogenesis, wherein HIV-1 co-infection accelerates and exacerbates disease progression. 271 METABOLIC ABNORMALITIES IN CD8 T CELLS FROM HIV+ INDIVIDUALS WITH KAPOSI SARCOMA Genevieve T. Clutton 1 , Michael McGrath 2 , Toby Maurer 2 1 University of North Carolina at Chapel Hill, Chapel Hill, NC, USA, 2 University of California San Francisco, San Francisco, CA, USA Background: A subset of HIV-infected individuals suffer from Kaposi Sarcoma (KS) despite viral suppression and CD4 recovery under anti-retroviral therapy

Poster Abstracts

269 WITHDRAWN KAPOSI SARCOMA–ASSOCIATED HERPESVIRUS IN AN HIV- INFECTED COHORT, SOUTH AFRICA Elizabeth M. Etta 1 , Lufuno G. Mavhandu-Ramarumo 1 , George Gachara 2 , Denise Tebit 1 , Wendell Miley 3 , Vickie Marshall 3 , Denise Whitby 3 , Pascal O. Bessong 1 1 University of Venda, Thohoyandou, South Africa, 2 Kenyatta University, Nairobi, Kenya, 3 AIDS and Cancer Virus Program, Frederick, MD, USA Background: Kaposi sarcoma associated herpesvirus (KSHV), is an oncogenic virus and a key determinant for Kaposi sarcoma development, particularly in individuals with prolonged immune suppression, for example HIV infected individuals. South Africa is highly endemic with HIV, with the potential for an epidemic of Kaposi sarcoma. For a better understanding of the consequence of KSHV and HIV co-infection, it is important to establish the burden of KSHV infection in South Africa, particularly in regions such as northern South Africa (Limpopo Province) which has a relatively high prevalence of HIV but where data on KSHV in the HIV population does not exist. We aimed at determining the sero-prevalence of KSHV K8.1 lytic and KSHV ORF73 latent antibodies in northern South Africa. Methods: A multi-district, cross sectional study was carried out in three thousand, five hundred and one plasma samples were retrospectively collected between September 2015 to February 2016, from HIV infected individuals from the five main districts comprising the Limpopo Province. Plasma samples were tested for antibodies to K8.1 and ORF73 antigens of KSHV by ELISA, using an in-house protocol developed by the Viral Oncology Section of the National Cancer Unit, USA. A sample was considered positive if antibodies to either of the antigens was detected. Distribution of infection was analyzed based on demographic, socioeconomic, and immunological parameters. Statistical inferences for significant differences were determined by Chi-square, at a confidence interval of 95%. P-values less than 0.05 were considered significant. Results: An overall prevalence of 18.9%was observed. Antibodies to both antigens were detected in 8.2% of the subjects. Prevalence of antibodies to the lytic antigen was significantly higher than prevalence of antibodies to the latent antigen (p=0.0001). Significant differences were observed for ORF73 antibody prevalence by ethnicity and year of sample collection (p=0.0001 and p=0.013 respectively). Although the prevalence of KSHV seropositivity in women was high for both antigens as compared to men, no significant difference was observed (p=0.921). No association was found between both antigens in comparison with the different variables (R2=0.1). Conclusion: This data has for the first time demonstrated a high seroprevalence of KSHV among the HIV infected population in northern South Africa. Infection with KSHV was observed to be associated with ethnicity. More findings are needed to conclude our findings.

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CROI 2019