CROI 2015 Program and Abstracts

Abstract Listing

Poster Abstracts

Conclusions: Key RAVs for HCV protease inhibitors are present in the majority of the HCV/HIV coinfected population prior to therapy. Correlation of Q80K with fibrosis stage suggests that compartmentalization within the liver may contribute to persistence of mutations less fit than wildtype. The prevalence of V36M and Q80K appears to be increased following therapy with PegIFN /ribavirin suggesting that pressure from non-targeted therapies could lead to selection. 699 Compensatory Mutations in HCV NS5A/B Coevolve in Patients Failing NS3 Inhibitors Velia Chiara Di Maio 1 ;Valeria Cento 1 ; Daniele Di Paolo 2 ; Sergio Babudieri 3 ; GloriaTaliani 4 ; Giustino Parruti 5 ; Giuliano Rizzardini 6 ; Mario Angelico 2 ; Carlo Federico Perno 1 ; Francesca Ceccherini-Silberstein 1 1 University of Rome Tor Vergata, Rome, Italy; 2 University Hospital of Rome Tor Vergata, Rome, Italy; 3 University of Sassari, Sassari, Italy; 4 University of Rome La Sapienza, Rome, Italy; 5 Pescara General Hospital, Pescara, Italy; 6 Hospital Sacco of Milan, Milan, Italy Background: The monocistronic structure of HCV genome may imply a coevolution of all genes during protease inhibitors (PI) failure. Our aimwas to analyze baseline to failure evolution of NS3/NS5A/NS5B in PI-failing patients. Methods: Twenty patients (15 GT1a; 5 GT1b) experiencing virological-failure with peg-IFN/riba+boceprevir (5), +telaprevir (13) or +simeprevir (2) were analyzed. NS3-protease, NS5A and NS5B sequences were obtained in all patients at baseline and at PI-failure, by population sequencing. Results: Subtyping information was confirmed by phylogenetic analysis of NS3, NS5A and NS5B sequences. Baseline NS3 (3GT1a=A421V, 1GT1b= A421V). Only one GT1a patient showed natural resistance simultaneously in NS3 (Q80K) and NS5A (L31M). At failure, all 15 GT1a and 4/5 GT1b patients presented major NS3 1=T54S+R155K; 1=T54A+R155T; 1=V55A+R155T; 3=R155K; 1b: 1=T54A+V170A; 1=F43C+T54S+A156T; 1=T54S+A156T+V170A; 1=A156T). NS5A/NS5B RAVs detected at baseline were still present and no other RAVs developed outside the NS3 region. However, 18/20 patients developed de novo NS5A mutations. Putative IFN-resistance associated NS5A-mutations remained unaffected by treatment-failure. Comparing baseline/failure sequences, statistically significant differences in entropy were observed only in NS3 RAV positions. Among GT1a patients, covariation analysis across all 3 genes showed several patterns of significantly associated mutations: NS3 Q80K was significantly associated with NS5A D441G (p=0.002,phy=0.87), as well as with NS5A R311Q and NS5B S506T (p=0.02,phy=0.70, for both cases). Instead, a negative association was observed for NS3 R155K and NS5B S506T (p=0.03,phy=-0.78). Interestingly, 2/3 GT1a patients with NS5B S506T failed without developing the classical NS3 R155K, but with the development of NS3 R155M and NS3 R155T+V55A, respectively. Conclusions: This proof-of-concept study shows that mutations in NS5A and NS5B may coevolve with NS3 RAVs during PI-treatment, potentially acting as compensatory mutations for viral fitness. RAVs were detected in 6/20 patients, all GT1a infected (1=V36L+Q80K, 4=Q80K, 1=R155K). In addition, 3/20 patients presented NS5A RAVs (1GT1a and 1GT1b=L31M, 1GT1b=Q54H) and 4/20 NS5B RAVs to non-nucleosidic inhibitors RAVs. Prevalence of resistance mutations changed according to subtype (1a: 1=V36L+R155M; 8=V36M+R155K/T; mutations (median[IQR] number=2[1-3]) and/or NS5B mutations (median[IQR]number=1[1-2]). 2 patients didn’t show any evidence of de novo NS5A/NS5B 2:30 pm– 4:00 pm Other Hepatitis Viruses: HBV, HDV, HEV 700 Hepatitis B Vaccine Response in Children Attending Rwanda Military Hospital Judy T. Orikiiriza 1 ; Louis Mujuwisha 2 ; Elizabeth Karlsson 3 ;Vincent Mutabazi 4 ; Johan Normark 3 1 Infectious Diseases Institute Makerere College of Health Sciences, Kampala, Uganda; 2 University of Rwanda, Kigali, Rwanda; 3 Umea Infectious Diseases Institute, Kigali, Sweden; 4 Rwanda Biomedical Center, Kigali, Rwanda Background: Hepatitis B virus (HBV) vaccine is protective in over 85% thus in most low resource settings (LRS) governments have endeavored to prioritize HB vaccination. There is paucity of information in LRSs concerning impact of HBV vaccination in pediatrics. Our general objective was to assess the humoral response to Hepatitis B vaccine in pediatric patients attending Rwanda Military Hospital. Methods: This was a prospective cross sectional study at Rwanda Military Hospital from October 2013 –December 2013. Children aged 3.5 months -18 years were enrolled consecutively after fulfilling the study criteria. A standardized questionnaire was used to capture demographic parameters of participants. Blood samples were removed to carry out HBsAg, antibodies to the HBsAg and HIV. Data was entered and analyzed using STATA version 1 2. Ethical approval was sought from the Institutional Review Board at RMH and College of Medicine and Health Sciences School of Medicine University of Rwanda. Results: Three hundred and four children were analysed, with a male: female ratio of 1.4:1, age range of 3.5 months to 18 years with a mean age of 7.88 years (SD= ± 5.5 years). Prevalence of HBV infection was 12/248(4.8%) and mean age of HBV infected children was 12.7 years (age range: 2.75-18 years). It was highest 9/12(75%) in >11-18 years age group with a male: female ratio of 10:2. HIV prevalence was found to be 1.6%with no HBV-HIV co-infection. Reported vaccination rate by the primary care taker was found to be 214/304(70.4%), 108/247(35.5%) were found to have Abs HBsAg titer >10IU that conferred protection. Protective vaccination titers were found to be 61.9% and 10.3% for ages between 3.5 months-11 year, >11year-18 years respectively. Of those reported to be vaccinated 59.9% had adequate Abs HBsAg titers and the proportion of Abs HBsAg levels decreased with increasing age with a p value<0.001. Conclusions: Abs to HBsAg wane with age amongst the vaccinated group and the commonest age group with high HB infection was in the older age thus there is need for providing HB vaccination boosters for the older age group to maximise HB prevention strategies. There is need to provide HB treatment beyond the HIV positive people as our study clearly demonstrates that those infected by HBV were all HIV negative. A larger study is recommended to determine the predictors of low HB antibody titers in our children and to come up with the appropriate timing for booster doses so that more relevant vaccine programs are rolled out. THURSDAY, FEBRUARY 26, 2015 Session P-N11 Poster Session Poster Hall

Poster Abstracts

433

CROI 2015