CROI 2018 Abstract eBook

Abstract eBook

Oral Abstracts

Results: 457/465 (98%) patients were male, median age was 41 years (IQR 38-46). Main routes of HCV transmission were MSM (98.9%) and IVDU (1.1%). 78.3% of patients were infected with HCV genotype (GT) 1, 2.6%with GT3 and 18.6%with GT4. Median baseline HCV-RNA was 230,000 IU/mL (135,000- 474,432) and median CD4+ T cell count 574 cells/µL (547-604). 92% of all patients received cART, 91% had baseline suppressed HIV-RNA (<200 copies/ mL). Median maximum ALT was 445 U/l (402-522). Overall, in 55/465 (11.8%) AHC resolved spontaneously. In 325/465 (69.9%) treatment was initiated within 48 weeks of AHC diagnosis, in 61 cases with interferon-free DAA regimen 24 weeks after acute HCV diagnosis. SVR rate was 75.7%. 51/465 (11%) patients were HCV reinfected. 85/465 (18.3%) developed chronic HCV infection. There was no statistically significant association between spontaneous clearance and HCV transmission risk, HCV GT, HCV RNA levels nor baseline ALT or HIV parameters. Conclusion: Spontaneous clearance of acute HCV infection in the setting of HIV coinfection is a rare event. Almost 90% of acutely infected patients face a chronic course. Therefore treatment initiation needs to be considered early on to prevent onward transmission to sex partners. As a result DAA drug labels as well as clinical guidelines need to be amended to allow usage of DAA during the acute phase of HCV infection in a high-risk population. 130 INTERNATIONAL VERSUS DOMESTIC HCV TRANSMISSION IN MSM: A PERSPECTIVE FOR THE DAA ERA Luisa Salazar-Vizcaya 1 , Roger Kouyos 2 , Karin Metzner 2 , Kamila Caraballo 3 , Cyril Shah 2 , Jürg Böni 2 , Manuel Battegay 4 , Enos Bernasconi 5 , Alexandra Calmy 6 , Matthias Cavassini 7 , Herbert A. Mbunkah 2 , Olivia Keiser 8 , Andri Rauch 1 1 University Hospital of Bern, Bern, Switzerland, 2 University Hospital Zurich, Zurich, Switzerland, 3 Medical University of Warsaw, Warsaw, Poland, 4 University Hospital Basel, Basel, Switzerland, 5 Servizio di Malattie Infettive, Lugano, Switzerland, 6 University Hospitals of Geneva, Geneva, Switzerland, 7 Lausanne University Hospital, Lausanne, Switzerland, 8 University of Geneva, Geneva, Switzerland Background: Rapid scale-up of early direct-acting antiviral (DAA) therapy for hepatitis C virus (HCV) in HIV-positive men who have sex with men (MSM) is ongoing in many European countries. It is expected to abate the high incidence of HCV associated with sexual practices. But isolated public health strategies in neighbouring countries might boost or hinder each other if international transmission is frequent. Switzerland is ideally placed to study international transmission due to its small population size and its high connectivity to international transmission networks. We used molecular epidemiology for estimating the contribution to the Swiss epidemic of HCV-infections acquired by contact with MSM from abroad, as a measure of potential vulnerability to foreign public health strategies. Methods: HCV subtype 1a genomes from 29 HIV-positive MSM with incident HCV infections were sequenced using Illumina technology (study sequences). Subtype 1a accounts for 62% of replicating infections in this population. Sampling dates ranged between 1999 and 2013. We used RAxML to infer maximum-likelihood phylogenetic trees containing a 436-base-pairs fragment of the NB5B region of the study sequences and other circulating strains (including 84 from other HIV+ people in Switzerland and 220 from across Europe). We established the likely geographic origin of infection (Swiss-to-Swiss versus imported transmissions) by inferring transmission clusters and locating the study sequences in such clusters. Sufficient degree of certainty was defined as a bootstrap value above 70%. Results: Ninety-seven percent of study sequences (28/29) were located in MSM clusters. Of those, ninety-six percent (27/28) were found amongst five transmission clusters within Europe (including Switzerland; Figure-A). Swiss-to- Swiss transmission was estimated to range between 38% and 76%. German- Swiss transmission was estimated to range between 7% and 41%. Transmissions linked to other European regions ranged between 0% and 28% (Figure-B). Conclusion: Swiss-domestic transmission of HCV subtype 1a is ongoing and therefore national treatment scale-up is expected to reduce HCV-incidence. But at least a quarter of sequenced infections were likely acquired by contacts with MSM from other European countries, in particular the neighboring country Germany. Our findings suggest the need for joint European scale-up schemes. Time-updated phylogenies are valuable for assessing the impact of national DAA scale-up programs.

Oral Abstracts

131 ITAP TRIAL: MATERNAL AND INFANT EFFICACY AND SAFETY RESULTS 12 MONTHS AFTER DELIVERY Gonzague Jourdain 1 , Linda J. Harrison 2 , Nicole Ngo-Giang-Huong 1 , Tim R. Cressey 1 , Luc Decker 1 , Camlin Tierney 2 , Jullapong Achalapong 3 , Prateep Kanjanavikai 3 , Anita Luvira 3 , Ussanee Srirompotong 3 , Trudy V. Murphy 4 , Noele Nelson 4 , George K. Siberry 5 , Stanislas Pol 6 1 IRD, Chiang Mai, Thailand, 2 Harvard University, Cambridge, MA, USA, 3 Ministry of Pubic Health, Nonthaburi, Thailand, 4 CDC, Atlanta, GA, USA, 5 NIH, Bethesda, MD, USA, 6 Cochin Hospital, Paris, France Background: iTAP was a double-blind randomized clinical trial assessing the efficacy and safety of tenofovir disoproxil fumarate (TDF) to prevent perinatal HBV transmission in hepatitis B virus (HBV) chronically infected pregnant women with HBeAg (NCT01745822). We report secondary endpoints through 12 months after delivery. Methods: HBsAg and HBeAg positive women (age ≥18 years, ALT ≤60 IU/L, negative HIV and hepatitis C serology, creatinine clearance >50 mL/min) were randomized to receive TDF 300mg or placebo, once daily from 28 weeks gestation through 2 months postpartum in 17 hospitals in Thailand. Infants received HBIg at birth, and HB vaccine at birth, 1, 2, 4 and 6 months of age. After their 6-month visit, mothers were seen at 12 months and infants at 9 and 12 months. Infant HBV DNA PCR was performed at 9 months and an HBsAg test at 12 months. Results: Of the 331 (168 TDF, 163 placebo) enrolled pregnant women, 282 (85%) (140, 83% TDF; 142, 87% placebo) remained in follow-up to 12 months postpartum. Median follow-up was 63 weeks. Time to grade 3/4 or serious adverse event in women was not different by arm (Figure). At scheduled study visits, ALT was >60IU/L for 76 women on 160 occasions in TDF and 86 women on 199 occasions in placebo. Nine women of 155 on TDF and 9 of 157 on placebo had ALT >300IU/L during follow up; with 9 (6%) and 6 (4%), respectively, after study treatment discontinuation (Fisher’s exact p=0.44). All ALT elevations were asymptomatic. Of 323 live births, 286 (89%) (146, 90% TDF; 140, 88% placebo) remained on follow-up until 12 months. One infant died (placebo) shortly after birth with multiple abnormalities. No other deaths occurred. Three infants (all placebo) were HBV infected by 6 months of age. No additional HBV infections were detected between 6 and 12 months. Of 275 infants evaluated for anti-HB antibodies at 12 months, 4 (all placebo) were <10 IU/L; including the 3 with HBV infection and one without HBV infection but a declining antibody level. The proportion of infants experiencing a grade 3/4 or serious adverse event was similar by arm (see Figure). Infants’ weight, height and head circumference Z-scores at 12 months did not differ by arm. Conclusion: Results were similar to those of the primary 6-month analysis. There were no statistically significant differences between the TDF and placebo arms in infant HBV infection or any secondary safety endpoints up to 12 months postpartum.

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CROI 2018