CROI 2017 Abstract e-Book

Abstract eBook

Poster and Themed Discussion Abstracts

infection confers a greater risk for accelerated progression to liver disease and death. To determine the prevalence of HDV in HIV positive and negative populations in Cameroon, HDV antibodies and RNA were characterized in 1701 HBsAg positive specimens, of which 846 (49.7%) individuals were co-infected with HIV. Methods: Plasma specimens were received from consenting subjects participating in surveillance studies in Cameroon collected over 8 years from 2007 – 2015. Samples were initially screened for antibodies (IgG) to HDV using a prototype HDV serology assay developed on the Abbott ARCHITECT. HDV reactive specimens with remaining volume were diluted 1:10 or 1:100 as necessary and screened using a prototype HDV RNA viral load assay with a calculated limit of detection of 5 IU/ml as calibrated by the HDV RNA WHO standard on the Abbott m2000 instrument. HDV RNA positive specimens with viral load >4.5 Log10 IU/ml were selected for complete genome Sanger sequencing of 3 overlapping regions, and a subset of specimens were selected for HIV or HBV sequencing for classification. All viral sequences were classified by phylogenetic analysis. Results: HDV IgG antibodies were detected in 683 (40.2%) specimens, and a majority of samples exhibited evidence of chronic infection with HDV RNA detected in 68% (n=455) of the 669 tested samples with available volume. The rate of chronic HDV infection may be underestimated due to sample dilution during processing. The seropositive rate of HIV/ HBV/HDV co-infection was 16.9% (288/1701), with 61.3% positive for HDV RNA. HDV/HBV/HIV co-infected specimens included HIV subtypes A, CRF02, CRF11, D, and G and HBV genotypes A and E. HDV genotypes 1, 6, and 7 were present in this population. Conclusion: HDV seroprevalence is high in HBsAg positive Cameroon individuals (40.2%), indicating that a large portion of HBV patients in Cameroon are at elevated risk for severe hepatitis and death. Screening and diagnosis of HDV in HBV/HIV-1 carriers in Cameroon might identify individuals at increased risk for developing liver disease. 578 WITHDRAWN 579 UNCONVENTIONAL T CELLS IN A PEG-INF-2Α ADD-ON STRATEGY FOR SUPPRESSED HBV INFECTION Camilla Tincati 1 , Elvira S. Cannizzo 1 , Francesca Binda 2 , Paola Ronzi 2 , Federico A. Cazzaniga 1 , Antonella d’Arminio Monforte 1 , Giulia Marchetti 1 , Laura Milazzo 2 1 Univ of Milan, Milan, Italy, 2 Luigi Sacco Univ Hosp, Milan, Italy Background: Eradication of chronic HBV (CHB) is rarely achieved with either nucleos(t)ide (NUC) analogues or pegylated interferon (Peg-IFN), yet encouraging results in terms of HBsAg decay and HBsAb seroconversion have emerged from small studies on the combined/sequential use of the two strategies. We hypothesized this may due to the adjuvant role of Peg-IFN during viral control and in particular to its influence on unconventional T-cells (iNKT, γδT) which bridge innate and adaptive responses. We therefore explored the effects of a Peg-IFN-2α add-on strategy to suppressive treatment with tenofovir (TDF) in CHB patients on the frequency and function of iNKT and γδT cells. Methods: 30 CHB, TDF-treated subjects, with HBV suppression for at least 2 years were randomized (1:2) at baseline (W0) to either receive Peg-IFN-2α add-on therapy (Add-On; n=10) for 48 weeks (W48) or continue TDF alone (Nuc; n=20). In a subgroup of 24 CHB (10 Add-On; 14 Nuc) and 8 HBV-uninfected subjects we studied γδT and iNKT frequency and function (flow cytometry) at W0 and W12. Wilcoxon, Mann-Whitney and Kruskall-Wallis tests were used for statistics. Results: Compared to controls, at W0, CHB subjects showed fewer iNKT (p=0.04), γδT (p=0.03) and Vδ2-expressing γδT populations (p=0.001) (Table). In contrast, no differences between groups were detected in cytokine-producing iNKT and γδT cells (Table). A greater HBsAg decay occurred in Add-On compared to Nuc at W12 (p=0.016) and W24 (intention-to-treat, p=0.01; on-treatment, p=0.001); HBsAg loss with HBsAb seroconversion was achieved in 2 Add-on and none Nuc. The addition of Peg-IFN-2α accounted for the decline in iNKT frequencies (p=0.0005) and expansion of cytokine-producing subsets (iNKT+IFN-γ+, p=0.03; iNKT+TNF-α+, p=0.006) (Table). A contraction of the γδT compartment was also observed (p=0.03), without modifications in cytokine expression (Table). No changes in iNKT and γδT cell surface and intracellular phenotype was detected in Nuc (Table). Conclusion: We show that virally-suppressed CHB subjects, compared to uninfected controls, display lower unconventional T-cells with preserved functional capacity. Further, our findings of a selective increase in iNKT function vis-à-vis the conserved cytotoxic potential of γδT during a Peg-IFN add-on strategy push the boundaries of existing knowledge on the possible immune determinants of HBsAg decay in this context, suggesting a critical role of iNKT in the clinical efficacy of combined treatment for HBV. 580 INCREASED RATES OF HBV SEROCONVERSION UNDER LONG-TERM HBV ACTIVE THERAPY IN HBV/HIV Christoph Boesecke 1 , Fabian Busch 1 , Clara Lehmann 2 , Carolynne Schwarze-Zander 1 , Jakob Malin 1 , Joerg Janne Vehreschild 2 , Jan-Christian Wasmuth 1 , Gerd Fätkenheuer 2 , Jürgen K. Rockstroh 1 , for the Cologne Bonn Cohort 1 Bonn Univ Hosp, Bonn, Germany, 2 Cologne Univ Hosp, Cologne, Germany Background: Patients with HIV have a 6x higher rate of developing chronic hepatitis B following acute HBV infection. Immune reconstitution under successful ART however, may increase the likelihood of clearing HBV infection successfully after prolonged dual HIV/HBV active nucleoside therapy. Data on rates of HBsAg loss over time under HBV nucleos(t)ide therapy are sparse. Here we evaluate rates of HBV seroconversion under HBV active ART in a large German cohort with a median follow-up of at least 8 years. Methods: Non-interventional retrospective cohort at 2 German academic HIV care centres assessing rates of HBV seroconversion defined as HBsAg loss in 95 HBV/HIV coinfected patients under HBV active (tenofovir (TDF) and/or lamivudine (3TC) containing) cART. Fisher’s exact, chi-square and Mann-Whitney U test were used for statistical analysis. Results: In total, 95 patients were included. 78% patients were male, median age was 40 years (IQR 34-45). 57%were of central European, 27% of African, 9% of Eastern, 5% of Southern European descent. Main routes of HIV transmission were MSM (43%), origin from high prevalence country (24%) and heterosexual intercourse (12%). CDC stage at HIV diagnosis was C3 in 25% followed by A2 (19%). 42.9%were ART-naïve when TDF and/or 3TC containing therapy was initiated (baseline). Median CD4 cell count at baseline was 270 (140-480). 54%were HBeAg positive at baseline. 95%were HBV PCR positive at baseline. 84% received TDF, 16% TDF and 3TC. 55% received a boosted protease inhibitor, 40% NNRTI and 5% an integrase inhibitor. Median follow-up was 107 months (76-144), median CD4 gain was 165 (3-315). Overall, HBV seroconversion (HBsAg loss) occurred in 15/95 (16%) patients. Median time to HBsAg loss was 35 months (18-49). There was no significant correlation between HBsAg loss and gender (p=0.562), age (p=0.677), country of origin (p=0.274), CDC stage (p=0.585), CD4 cell count (p=0.249), CD4 gain (p=0.7), HBeAg (p=0.712), receiving TDF or TDF/3TC (p=0.576) or ART class (p=0.582). Conclusion: HBV seroconversion defined as HBsAg loss is occurring at a much higher rate in HBV HIV coinfected patients even after years on HBV active ART when compared to published seroconversion rates of 4.5% over 96 weeks from the extension phase III tenofovir trials in HBV monoinfected subjects. Positive predictors remain unclear to date but immunreconstitution under ART appears to allow better control of HBV infection. 581 MORTALITY OF HIV/HBV COINFECTED PATIENTS ON ART IN URBAN AND RURAL SOUTHERN AFRICA Jonas Hector 1 , Michael J. Vinikoor 2 , Kalo Musukuma 2 , Roma Chilengi 2 , Laura Jefferys 3 , Michael A. Hobbins 1 , Mary-Ann Davies 4 , Matthias Egger 5 , Gilles Wandeler 5 1 SolidarMed, Luzern, Switzerland, 2 Cntr for Infectious Disease Rsr in Zambia, Lusake, Zambia, 3 SolidarMed, Pemba, Mozambique, 4 Univ of Cape Town, Cape Town, South Africa, 5 Univ of Bern, Bern, Switzerland Background: Chronic hepatitis B virus (HBV) infection affects 10% of HIV+ people in sub-Saharan Africa (SSA) and is an important cause of liver disease in this population. Due to high rates of losses to follow-up (LTFU), precise mortality estimates among cohorts of patients on antiretroviral therapy (ART) in the region are scarce. We compared one-year mortality of HIV/HBV-coinfected patients on tenofovir-containing ART between rural and urban primary care clinics after systematic tracing of patients LTFU. Methods: We enrolled HIV/HBV coinfected adults initiating ART at two urban clinics in Zambia and three rural clinics in Mozambique between May 2013 and July 2015. Quantitative real-time PCR for HBV viral load was performed using the COBAS Ampliprep/TaqMan System and HBV sequencing according to an in-house protocol. Medication possession ratio (MPR; proportion of follow-up days with ART possession) was used as a proxy for adherence. All patients LTFU (>3 months without a clinical visit) were traced by phone and home visits for ascertainment of vital status. Baseline characteristics were evaluated using Fisher`s exact test and Wilcoxon rank sum tests. Mortality rates and associated risk factors were assessed using multivariable Cox proportional hazards regression.

Poster and Themed Discussion Abstracts

CROI 2017 244