CROI 2015 Program and Abstracts

Abstract Listing

Poster Abstracts

701 Revaccinating HIV+ Adults With Double vs Standard HBV Regimen: ANRS B-BOOST Trial David Rey 1 ; Cécilie Dufour 2 ; Marie-JoséeWendling 3 ; Patrick Miailhes 4 ; Philippe Sogni 8 ; Georges Haour 2 ; Marie-Louise Michel 7 ; Lionel Piroth 6 ; Odile Launay 5 ; Fabrice Carrat 2 1 University Hospital Strasbourg, Strasbourg, France; 2 Université Pierre et Marie Curie, Strasbourg, France; 3 Hôpitaux Universitaires Strasbourg, Strasbourg, France; 4 University Hospital of Lyon, Lyon, France; 5 CIC Vaccinologie, Paris, France; 6 University Hospital of Dijon, Dijon, France; 7 Institut Pasteur, Paris, France; 8 Cochin Hospital, Paris, France Background: Immune response to standard hepatitis B (HBV) vaccination is decreased in HIV-infected patients, and it has been recently shown that a double dose HBV primary vaccination regimen improved serological response. However, the immunogenicity of this regimen in non responders to a previous vaccination is unknown. Methods: In an open-label, multicenter, 1:1 parallel groups randomized clinical trial, stratified according to CD4 cell count (200-349, and > 350 cells/ μ l), 411 HIV-infected adults, CD4 T cells ≥ 200/ μ l, and previously vaccinated against HBV, without HBV markers, received a booster dose (20 μ g) of HBV vaccine. 178 of themwho did not respond to the boost were randomized to receive HBV vaccination with either 3 intramuscular (IM) standard doses (20 μ g, group A, n=90), or 3 IM double doses (40 μ g, group B, n=88) at weeks 0, 4 and 24. Subjects with anti-HBs ≥ 10 mUI/mL and ≥ 100 mUI/mL at week 28 were defined as responders (main endpoint) and high responders, respectively. Results: The median age of the population was 44 years (IQR 40-51); 78%were male; the median CD4 cell count was 512 cells/ μ l (IQR 424-682); 71% had plasma viral load < 50 copies/ml. In an intent-to-treat analysis (missing = failures), the percentage of responders and high responders were 67% and 26% in group A, 74% and 47% in group B (P=.33 and P=.002). At week 28, the geometric mean titre of anti-HBs were 20 and 60 mUI/mL in group A and B respectively (P=.0004). BMI was the only factor associated with response to vaccination (>=25 vs <25, odds-ratio=2.42; 95%CI (1.1-5.3) P=.028). Among responders at week 28, 43% and 64% in group A and B respectively, had anti-HBs ≥ 10 mUI/mL at week 72 (p=.0069), and geometric mean titre of anti-HBs were 11 and 35 mUI/mL (p=.0016) in group A and B at week 72. There were two serious adverse events associated with the vaccine (1 in each group): exacerbation of psoriasis and severe headaches. Local reactions occurred in 5% of patients in group A versus 15% in group B (P=.02). Conclusions: In HIV-1 infected adults who did not respond to a standard dose HBV vaccination, a double-dose re-vaccination regimen does not increase the response rate but provides higher level of anti-HBs titre, with longer durability, compared with a standard re-vaccination regimen. 702 Complex HBV Quasispecies Affects Immunogenicity in Acute Hepatitis B Infection Valentina Svicher 1 ; Marianna Aragri 1 ; Nicola Coppola 2 ; Claudia Alteri 1 ; Arianna Battisti 1 ; Caterina Sagnelli 2 ; Mariantonietta Pisaturo 2 ; MariaConcetta Bellocchi 1 ; Evangelista Sagnelli 2 ; Carlo-Federico Perno 1 1 University of Rome Tor Vergata, Rome, Italy; 2 Second University of Naples, Naples, Italy Background: To identify HBV RT and HBsAg quasispecies heterogeneity in patients with acute hepatitis B (AHB) and to define their clinical value. Methods: This study included 62 HBsAg+ and IgM/anti-HBc+ patients with clinical and biochemical signs of AHB (44 infected by genotype [gen] D and 18 by gen A) observed from 2000 to 2010. Ultra-deep sequencing (UDPS) was performed on plasma samples obtained at first observation. Drug-resistance and immune-escape mutations were retrieved from literature. Shannon Entropy (weighted for the intra-patient prevalence of each mutated position) was used to measure the extent of amino acid variability of HBsAg positions. Results: 75.8% of patients were male with median (IQR) age of 36(29-46)years. Median (IQR) ALT and median (IQR) serum HBV-DNA were 2,544(1,938-3,078)U/L and 5.88(4.47- 7.37)log 10 IU/ml. 61/62 became HBsAg-negative with 33/61 developing anti-HBs (marker of full immune control). By UDPS, drug resistance mutations (rtV173L/rtL180M/rtA181T/rtA194T/rtM204I) were detected in 8.1% of patients with an intra-patient prevalence ranging from 0.11% for rtA181T to 99.98% for rtL180M. UDPS also detected >1 immune-escape mutation within the a-determinant in 48.4% of patients with an intra-patient prevalence from 0.16% to 100%. Among them, vaccine- escape mutations were found only in gen D. This is the case of sG145R, sM133L, and sP120S, detected in 11.4% of patients, with an intra-patient prevalence ranging from 3.9% to 99.9% for sG145R, from 1.9% to 16.8% for sM133L, and from 100% to 100% for sP120S. Similarly, stop-codons were found in 19.3% patients (intra-patient prevalence range:1.6%-47.5%). They occurred at 11 HBsAg positions including 172 and 182 known to correlate with an increased HBV oncogenic potential. Finally, in gen D, an higher Shannon Entropy at specific HBsAg positions correlated with no anti-HBs production. Among them, positions 130 and 133 (localized in HLA class II epitope ranging aa 124-137) were found mutated only in patients not developing anti-HBs (1.98 ± 0.011 vs 0, and 1.95 ± 0.033 vs 0, respectively, P<0.05). Conclusions: A substantial fraction of AHB-patients is characterized by a complex viral quasispecies with reduced antigenicity/immunogenicity, enhanced oncogenic-potential and/or altered drug-susceptibility. These viral variants may potentially expose patients to severe and/or difficult-to-treat forms of HBV-infection (also in the setting of HBV reactivation), and may affect the efficacy of current HBV vaccination strategy. 703 Higher Rate of Hepatitis B Antigen and Anti-HBV Antibody Seroconversion Among HIV/Chronic Hepatitis B Coinfection Initiating HBV Active HAART From Thailand Anchalee Avihingsanon 1 ; Opass Putcharoen 2 ; Salyavit Chittmittrapap 2 ;Tanakorn Apornpong 1 ;Vorapot Sapsirisavat 1 ; Sasiwimol Ubolyam 1 ; Stephen J. Kerr 1 ; Kiat Ruxrungtham 1 On behalf of the HIV-NAT 105 StudyTeam 1 HIV Netherlands Australia Thailand Research Collaboration, Thai Red Cross - AIDS Research Centre, Patumwan, Thailand; 2 Chulalongkorn University, Bangkok, Thailand Background: Hepatitis B surface antigen (HBsAg) loss is considered the ideal outcome of chronic hepatitis B virus (HBV) infection. HBsAg loss was reported in 12% of subjects from a Caucasian HIV/HBV cohort. We investigated the rate and predictors of HBsAg loss and antiHBs Ab seroconversion among 213 HIV/HBV coinfected patients from Thailand. Methods: Subjects with confirmed chronic HBV infection (HBsAg positive results >6 months apart) were selected from the cohort. Serial HBV serology, HBV DNA, quantitative HBsAg and liver biochemistry were performed. Results: Of 213 subjects enrolled, median age was 42 (IQR 36 – 48) years, 69%were male. At start of ART, CD4 cell count was 242 (IQR 107-371) cells/ mm 3 . At the most recent visit, median CD4 cell count was 523 cells/mm 3 , 84% had undetectable HIV RNA, 56%were HBeAg positive and 82.4% had HBV genotype C. Median baseline HBV DNA was 7.2 (IQR 3.2-7.5) log 10 IU/mL. Loss rate of HBeAg (for HBeAg positive cases) and HBsAg were 44% and 17.4%, respectively. The incidence of HBsAg conversion was 2.93(2.13-4.05) per 100 PY. 15/37 patients (40.5%) developed antiHBsAb conversion at a median duration of 163 weeks after ART. Baseline demographic data was comparable between those with and without HBsAg loss. Median duration on ART was 9 (IQR 3-14) years, with 68.5% on ART for >5 years. However, duration of ART was longer for those with HBsAg loss (12 vs 8 yrs). Overall, 80.2% had HBV DNA <10 IU/mL at the most recent clinic visit. 27 and 8 patients were on low dose and discontinued of tenofovir, respectively, due to falling eGFR. All of these had HBV DNA < 10 IU/mL at last visit. HBsAg loss was associated with younger age [harzard ratio:HR 0.94 (95% confidence interval:95% CI 0.89-0.99), p=0.019] and normal ALT [HR 3.16 ( 95% CI 1.11-9.02)]. In a subgroup with available HBsAg that had been quantitated, levels >100 IU/mL [HR 0.02 (95%CI 0.03-0.21), p<0.001] was associated with a lower clearance of HBsAg than those with levels ≤ 100 IU/mL in adjusted analyses. Conclusions: Rate of HBsAg loss, HBeAg and antiHBsAb seroconverstion in these Asian HIV/HBV coinfected individuals initiating HBV active ART were high. Older age and abnormal ALT were associated with reduced HBsAg clearance. This population is a promising target for studies exploring intensive biomarkers for potential HBV cure.

Poster Abstracts

434

CROI 2015