CROI 2016 Abstract eBook

Abstract Listing

Poster Abstracts

326 CD4/CD8 Ratio and K/T Ratio Predict Yellow Fever Vaccine Response in HIV+ Patients Vivian I. Avelino-Silva 1 ; KarinaT. Miyaji 1 ; Marcos S. Freire 2 ; Ana M. Sartori 1 ; PeterW. Hunt 3 ; HuangYong 3 ; Ester C. Sabino 1 ; Dayane A. Costa 1 ; Juliana Z. Dias 1 ; Esper G. Kallas 1 1 Univ of Sao Paulo Med Sch, Sao Paulo, Brazil; 2 Fundação Oswaldo Cruz, Rio de Janeiro, Brazil; 3 Univ of California San Francisco, San Francisco, CA, USA Background: Weaker immune responses to Yellow Fever vaccine (YFV) in HIV-infected persons may be influenced by chronic immune activation. Indoleamine 2,3-dioxygenase-1 (IDO) catabolizes tryptophan (T) to kynurenine (K) and other metabolites that may contribute to proliferative lymphocyte defects, microbial translocation and immune activation in treated HIV infection. Low CD4/CD8 ratio is strongly associated with IDO activity and may also be a marker of adaptive immune dysfunction in this population. Methods: We prospectively assessed YFV viremia and YF-specific antibodies (NAb) in HIV-infected (CD4>350) and –uninfected adults on days 0, 3, 5, 7, 14, 28, 56, 84, and 365 after YFV. We assessed CD4/CD8 ratio, GBV-c viremia and IDO activity (as measured by plasma K/T ratio) as potential predictors of NAb in the first year after YFV with linear mixed models. Results: Among 12 HIV-infected and 45 -uninfected participants, median age was 33 and 43 years old, and most were men. Groups had similar percentages of previous YFV. Compared to HIV-uninfected participants, those with HIV had lower median CD4 counts (722 vs 941 cells/mm 3 , P=0.003), lower CD4/CD8 ratios (0.7 vs. 1.6, P<0.0001), a trend toward higher K/T ratio (36 vs. 31 nM/µM, p=0.06), and a higher prevalence of detectable GBV-C viremia (66.7% vs. 26.7%, p=0.016). HIV status was not associated with the occurrence or levels of YFV viremia, or with the occurrence of adverse events after YFV. HIV status was not associated with difference in NAb titers in the visits up to day 84, but predicted lower NAb titers at 1 year after YFV (fold-change 0.32, 95% CI 0.13 to 0.83, p=0.021), independent of sex, age and previous YFV. Among HIV-infected participants, higher CD4/CD8 ratio predicted higher NAb titers; for each 10% increase in CD4/CD8 ratio, post-baseline NAb titers were 14% higher (95% CI 1 to 26, p<0.03). Similarly, higher K/T ratio predicted lower Nab titers; for each 10% increase in K/T ratio, post-baseline antibody titers were 21% lower (95% CI 5 to 37% lower, p=0.02). GBV-c viremia was not associated with difference in NAb titers. Conclusions: Despite similar responses in the initial 3 months, NAb to YFV were less durable among HIV-infected persons. CD4 + /CD8 + ratio and K/T ratio at vaccination predict NAb among HIV-infected participants, suggesting immune activation and/or dysfunction impairs YFV response in this population. 327 Steady State and Post-Vaccination TFH Dynamics in HIV Patients TreatedWith cART Eirini Moysi 1 ; Louis Edward Gonzalez 2 ; Lesley De Armas 3 ; Joseph P. Casazza 4 ;Varghese K. George 5 ; Rajendra Pahwa 2 ; Suresh Pallikkuth 3 ; Richard A. Koup 4 ; Costantinos Petrovas 6 ; Savita Pahwa 2 1 Univ of Miami, Miller Sch of Med, Bethesda, MD, USA; 2 Univ of Miami, Miller Sch of Med, Miami, FL, USA; 3 Miller Sch of Med, Univ of Miami, Miami, FL, USA; 4 VRC, NIAID, NIH, Bethesda, MD, USA; 5 Univ of Miami, Miami, FL, USA; 6 NIH, Bethesda, MD, USA Background: HIV infection dramatically changes the lymph node (LN) tissue architecture and the dynamics of tissue resident immune cells, potentially affecting the ability of HIV infected individuals to respond to subsequent antigenic challenge. The dynamics of circulating and LN-resident CD4 T cell and B cell populations in cART HIV patients after trivalent seasonal influenza immunization were assessed. Methods: LN-derived cells and PBMCs from healthy controls and virologically suppressed HIV+ patients were obtained pre- and post- vaccination and analyzed using multiparametric flow cytometry assays and multiplexed confocal imaging. Fluidigm gene expression analysis was performed to assess the effect of vaccination on the transcriptional profile of follicular CD4 T cells. Actively transcribed virus in sorted LN-cells was analysed by PCR assays. Results: Pre-vaccination frequencies of follicular CD4 T helper cell (T FH ) between healthy donors and cART HIV+ patients at steady state were collectively similar but were highest in those with the greatest increase in antibody titers post-vaccination. This profile was also reflected at tissue level when relevant populations were investigated with imaging assays. There was a trend for lower T FH frequencies post-vaccination in HIV+ compared to HIV- individuals while B cell frequencies remained the same post-vaccination both in LN and PBMC. The transcriptional profile of T FH revealed differentially expressed genes (DEGs) between HIV- and cART treated donors. Furthermore, our transcriptional analysis revealed that vaccination had a greater impact on T FH compared to non-T FH CD4 T cells. In line with the lower frequencies of T FH , actively transcribed virus in the T FH compartment was reduced after vaccination. Conclusions: Vaccination predominantly alters the frequency and phenotype of follicular CD4 T-cells in the draining LN of HIV infected patients on cART in a manner consistent with the development of IgG antibody titers. The underlying mechanism of follicular CD4 T cell mobilization warrants further investigation as it could bear implications for the rational design of HIV vaccines. 328 WITHDRAWN 329 Impaired Responses to Vaccine in HCV Infection Are Related to Baseline Inflammation Carey L. Shive 1 ; Chelsey Judge 2 ; Robert Kalayjian 3 ; Melissa Osborn 3 ; Kenneth E. Sherman 4 ; Carl Fichtenbaum 4 ; Daniel Popkin 2 ; Scott M. Sieg 2 ; Benigno Rodriguez 5 ; Donald Anthony 1 1 Cleveland VA Med Cntr, Cleveland, OH, USA; 2 Case Western Reserve Univ, Cleveland, OH, USA; 3 MetroHlth Med Cntr, Cleveland, OH, USA; 4 Univ of Cincinnati, Cincinnati, OH, USA; 5 Case Western Reserve Univ Sch of Med, Cleveland, OH, USA Background: Chronic HCV and HIV infection are associated with impaired responses to HAV/HBV vaccines. HAV and HBV infections augment hepatic damage in HCV-infected individuals and HIV disease progression is associated with HBV and HCV coinfection. Understanding why these populations fail to respond effectively to neo-antigen vaccines is necessary to guide strategies to improve these prophylactic vaccine responses. Methods: This study was designed to examine HAV/HBV vaccine responsiveness in untreated HCV (n=15), untreated HIV (n=24), and uninfected (n=10) participants. Baseline levels of soluble factors of inflammation were measured by ELISA and HAV and HBV antibody titers were measured at wk1, 3, 8, and 24 after vaccination with the HAV/HBV vaccine, Twinrix. Results: The proportion of HIV-infected participants who failed to respond to vaccine with an antibody response within 8 weeks post-vaccination to HAV (20%) and HBV (62%) was greater than the proportion of HCV-infected participants (HAV 0%, HBV 21%) or uninfected controls (HAV 0%, HBV 20%). We found that baseline plasma levels of IP10 and IL-6 were elevated in HCV (p=<0.001) and HIV-infected participants compared to uninfected controls, and in HCV-infected participants plasma levels of IP10 inversely correlated with week 8 antibody responses to HAV (r= -0.762 p= 0.037). Plasma levels of IL-6 inversely correlated with week 8 HBV antibody responses (r= -0.728 p= 0.004). Despite elevated plasma levels of IP10 and IL-6 in HIV-infected participants, levels did not correlate with vaccine antibody response, likely because of the low proportion of participants responding to the vaccine. In HCV-infected participants plasma levels of soluble CD163 (sCD163) were elevated at baseline compared to plasma levels in uninfected controls and untreated HIV- infected participants. Soluble CD163 correlated inversely with week 8 HBV antibody levels in HCV-infected participants (r= -0.643 p=0.015). Conclusions: Elevated baseline levels of soluble factors of inflammation are predictive of poor vaccine response to HAV/HBV neo-antigen vaccine during chronic HCV infection. 330 Persistence of HIV-Infected Alveolar Macrophages After Suppressive ART Feiyu Hong ; Heather M. Michael; Shulin M. Qin; Lawrence Kingsley; Deborah McMahon; Meghan E. Fitzpatrick; Alison Morris; JohnW. Mellors Univ of Pittsburgh, Pittsburgh, PA, USA Background: Although HIV-1 infection in macrophages is documented among viremic individuals, there is no conclusive evidence for long-term HIV persistence in these cells during suppressive ART. Here, we analyzed highly-purified alveolar macrophages (AM) for evidence of HIV-1 infection and transcriptional activity in vivo .

Poster Abstracts

125

CROI 2016