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819
ANALYSIS OF HBsAg ISOFORMS DURING AND AFTER NAPBASED
COMBINATION THERAPY IN THE REP 301, REP 301-LTF
AND REP 401 STUDIES
Michel Bazinet1, Mark Anderson2, Victor Pântea3, Gheorghe
Placinta4, Iurie Moscalu5, Valentin Cebotarescu3, Lilia
Cojuhari3, Pavlina Jimbei6, Liviu Iarovoi4, Valentina Smesnoi6,
Tatiana Musteata6, Alina Jucov7, Jeffrey Gersch2, Vera
Holzmayer2, Mary Kuhns2, Gavin Cloherty2 and Andrew
Vaillant1, (1)Replicor Inc., (2)Abbott Diagnostics, Abbott
Park, IL, USA, (3)Department of Infectious Diseases, Nicolae
Testemiţanu State University of Medicine and Pharmacy, (4)
Department of Infectious Diseases, Nicolae Testemitanu
State University of Medicine and Pharmacy, (5)Spitalul Clinic
Republican, Moldova, (6)Toma Ciorbă Infectious Clinical
Hospital, (7)Nicolae Testemitanu State University of Medicine
and Pharmacy of the Republic of Moldova
Background: In HBeAg negative HBV mono-infection, NAP
combination therapy achieved 78% virologic control (HBV DNA
≤ 2000 IU/mL, normal ALT [VC]) with 39% further achieving
functional cure (HBsAg < 0 05 IU/mL, HBV DNA target not
detected, normal ALT [FC]) (REP 401 study, NCT02565719)
Retrospective inclusion of participants with HBeAg negative
HBV / HDV co-infection receiving suboptimal NAP-based
combination therapy (REP 301 study, NCT02233075 and
REP 301-LTF study, NCT02876419) yielded combined HBV
outcomes of 18/52 (35%) FC, 19/52 (36%) VC and 15/52
(29%) rebound (R) The goal of this study was to analyze
the dynamics of S-HBsAg, M-HBsAg and L-HBsAg during
and after NAP therapy in the REP 301 / 301-LTF and 401
studies Methods: Frozen serum samples (n=1153) from all
52 participants in the REP 301 / REP 301-LTF and REP 401
studies were analyzed using the Abbott research use only
(RUO) assays for HBsAg isoforms (large [L], medium [M] and
total [T]) T-HBsAg was used to assess total HBsAg present
From this population of HBsAg, the presence of M-HBsAg
and L-HBsAg was determined The relative change over time
in S-HBsAg relative to the other isoforms was inferred by
the change in the ratio over time of T-HBsAg to M-HBsAg
Measurements with S/Co < 1 were excluded from the ratio
/ trend analysis Results: qHBsAg reduction from baseline
> 2 log10 IU/mL was observed in 40/52 participants A more
rapid reduction of S-HBsAg relative to the reduction of other
HBsAg isoforms occurred in 37/40 of these participants,
consistent with the selective targeting of SVP assembly and
secretion by NAPs Selective S-HBsAg loss was not observed
in 11/12 participants with qHBsAg reduction ≤ 2log10 from
baseline, suggesting the more moderate HBsAg responses
were due to suboptimal inhibition of SVP assembly At the
end of follow-up, all HBsAg isoforms were detectable (S/
Co > 1) in 0/18 (FC), 17/19 (VC) and 15/15 (R) participants.
Conclusion: Selective effects on S-HBsAg clearance during
NAP therapy are consistent with selective inhibition of SVP
assembly and secretion on human HBV infection during NAP
therapy Suppression of all HBsAg isoforms during follow-up
in participants establishing functional cure indicate the control established is profound. |
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