CROI 2017 Abstract e-Book

Abstract eBook

Poster and Themed Discussion Abstracts

Results: Antibodies to HPgV-2 were infrequently found in all subject groups tested, with the highest prevalence in HCV co-infected (3.31%). This is in stark contrast to HPgV-1 infection where all groups screened had antibodies with the highest prevalence found among HCV and HIV groups (48.76% and 41.71 %). Active cases of HPgV-2 infection, with viral loads ranging from 2.2-6.6 log copies/ml, were found primarily in samples with HCV antibodies; one has been found in an acute case, and another in a resolved HCV infection. Similar to HCV, HPgV-2 viremia was strongly associated with the presence of HPgV-2 antibodies. This is in contrast to HPgV-1 where simultaneous detection of viral RNA and E2 antibodies is predominantly exclusive. Strains identified thus far share approximately 94% nucleotide identity to one another and cluster tightly in a deep clade most closely related to bat and rodent pegiviruses. Conclusion: HPgV-2 infection occurs alongside HCV infection. Whether HPgV-2 is pathogenic on its own or exacerbates HCV-related disease will be addressed with future studies. Due to its low prevalence, high throughput diagnostic tools will facilitate global surveillance to further assess prevalence and the diversity present in this novel human virus. 584LB TDF TO PREVENT PERINATAL HEPATITIS B VIRUS TRANSMISSION: A RANDOMIZED TRIAL (ITAP) Gonzague Jourdain 1 , Nicole Ngo-Giang-Huong 1 , Linda J. Harrison 2 , Luc Decker 1 , Camlin Tierney 2 , Tim R. Cressey 3 , Jullapong Achalapong 4 , George K. Siberry 5 , Noele Nelson 6 , Nantasak Chotivanich 7 1 IRD, Chiang Mai, Thailand, 2 Harvard Univ, Boston, MA, USA, 3 Prog for HIV Prevention and Treatment, Chiang Mai, Thailand, 4 Chiangrai Prachanukroh Hospl, Chiang Rai, Thailand, 5 NIH, Bethesda, MD, USA, 6 CDC, Atlanta, GA, USA, 7 Chonburi Hospital, Chonburi, Thailand Background: Pregnant women with high hepatitis B virus (HBV) DNA load still transmit to their infants despite infant HB immunoglobulin (HBIg) and HB vaccine. Methods: This phase III, double-blind, clinical trial randomized pregnant women with HBV infection (HBsAg and HBeAg positive) to tenofovir DF (TDF) 300 mg once daily or matching placebo (1:1) from 28 weeks gestation through 2 months postpartum in 17 sites in Thailand. All infants received HBIg at birth, and vaccine at birth, 1, 2, 4 and 6 months of age. Main inclusion criteria were: age ≥18 years, confirmed ALT ≤60 IU/L, negative HIV and hepatitis C serology, creatinine clearance >50 mL/min, and no history of TDF treatment. Mothers and infants were followed until 12 months postpartum. The primary efficacy endpoint was detection of HBsAg confirmed by HBV DNA at 6 months of age. The target sample size was 156 evaluable mother/infant pairs per arm to detect a difference in HBV infected infants of 3% (TDF) vs. 12% (placebo) with 90% power accounting for one interim efficacy analysis, using a one-sided Fisher’s exact test. Analyses are based on data through 6 months postpartum. Results: From January 2013 to August 2015, 331 women (168 TDF, 163 placebo) were enrolled. Median age at enrollment was 26 years, gestational age (GA) 28.3 weeks, weight 61 kg, and HBV DNA load 8.0 log 10 IU/mL. The 322 (97%) on-study deliveries (85 Cesarean, 26%) resulted in 323 live births (including 2 twin pairs) and 1 stillbirth (TDF arm). Median GA at delivery was 38.9 weeks. Median birth weight was 3,050 g (3,028 g TDF, 3,061 g placebo). There were 21 (7%) preterm newborns (8 TDF, 13 placebo). 322 (>99%) infants received HBV vaccine a median of 1.2 hrs. after birth and 320 (99%) HBIg a median of 1.3 hrs. after birth. In the primary complete case analysis at 6 months (table), 0/147 infants had HBV infection in the TDF arm vs. 3/147 (2.0%) in the placebo arm (p=0.12). One newborn with gross abnormalities (placebo arm) died soon after birth. Following study treatment discontinuation, 9 (6%) women experienced an ALT >300 IU/mL in the TDF arm vs. 5 (3%) in the placebo arm (two-sided p=0.29). The proportions of maternal and infant adverse events, and infant growth were similar between arms. Conclusion: TDF resulted in a small non-significant reduction in perinatal HBV transmission beyond the low risk achieved with the recommended use of HBIg and HBV vaccine. It appeared safe for pregnant women and their infants and there was no evidence of impaired infant growth.

Poster and Themed Discussion Abstracts

585 EFFECTS OF TREATMENT WITH MARAVIROC A CCR5 INHIBITOR ON HUMAN HEPATIC STELLATE CELLS Salvatore Martini 1 , Angelica Perna 1 , Angela Lucariello 1 , Margherita Macera 1 , Maria Aurora Carleo 2 , Germano Guerra 3 , Vincenzo Esposito 2 , Antonio De Luca 1 , Nicola Coppola 1 1 Second Univ of Naples, Naples, Italy, 2 AORN dei Colli, Naples, Italy, 3 Univ of Molise, Campobasso, Italy Background: After an acute liver damage, tissue regeneration repairs lesions with degradation of deposed fibrotic material, while mechanisms of tissue restoration are persistently activated following several repeated injuries, inducing deposition of extracellular matrix. (ECM). Factors responsible for ECM remodeling have been identified in a pathway involving a family of zinc-dependent enzyme matrix metalloproteinases (MMPs), together with tissue inhibitor of metalloproteinases (TIMPs). Recent experimental models suggested a role of CCR5 receptor in the genesis of liver fibrosis. We evaluated the effects of the treatment with the CCR5 inhibitor Maraviroc on LX-2, a human hepatic stellate cell line (HSC), derived from normal human stellate cells spontaneously immortalized. Methods: LX-2 viability was determined using MTT [3-(4,5-dimethylthiazol-2- yl)-2,5-diphenyltetrazolium bromide]; the cells, pretreated with Maraviroc and TGF-β1, have been studied by Western blot assay to evaluate the expression of cyclin D1, p21, p53, collagen type I, ∝-SMA, TGF-β1. The expression of MMP-2, MMP9, TIMP-1 and TIMP-2 were evaluated by RT-PCRs in correlation to GADPH expression to standardize differences in the quantity of cDNA used in the PCR reaction.

CROI 2017 246