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LBP33
Analysis of HBsAg levels, HBsAg isoforms, HBsAg immune
complexes, HBV pregenomic RNA and HBcrAg dynamics during
and after NAP-based combination therapy in the REP 301-LTF and
REP 401 studies
Michel Bazinet1, Mark Anderson2, Victor Pantea3, Gheorghe Placinta3,
Iurie Moscalu4, Valentin Cebotarescu3, Lilia Cojuhari3,
Pavlina Jimbei5, Liviu Iarovoi3, Valentina Smesnoi5, Tatiana Musteata5,
Alina Jucov3,4, Jeff Gersch2, Vera Holzmayer2, Mary Kuhns2,
Gavin Cloherty2, Andrew Vaillant1. 1Replicor Inc., Montreal, Canada;
2Abbott Diagnostics, Illinois, United States; 3Nicolae Testemiţanu State
University of Medicine and Pharmacy, Department of Infectious
Diseases, Chișinău, Moldova; 4ARENSIA Exploratory Medicine,
Republican Clinical Hospital, Chișinău, Moldova; 5Toma Ciorbǎ
Infectious Clinical Hospital, Chișinău, Moldova
Email: [email protected].
Background and aims: After completion of NAP-based combination
therapy with pegIFN and follow-up in the REP 301-LTF study (3.5
years) and REP 401 study (48 weeks), combined HBV outcomes were
functional cure (HBsAg <0.05 IU/mL, HBV DNA target not detected,
normal ALT [FC]) in 18/52 (35%), virologic control (HBV DNA
≤2000 IU/mL, normal ALT [VC]) in 19/52 (36%) and rebound (R) in
15/52 (29%) of participants. The goal of this study was to analyze the
relationship between HBV outcome and experimental virologic
markers of HBV infection.
Methods: Frozen serum samples (n = 1153) from all 52 participants in
the REP 301/REP 301-LTF and REP 401 studies were analyzed by the
following:
1. Abbott ARCHITECT HBsAg NEXT (analytical sensitivity 0.005 IU/
mL).
2. Abbott research use only (RUO) assays for HBsAg isoforms (large,
medium, small).
3. Abbott RUO assay for HBsAg/anti-HBs immune complexes
(HBsAg IC).
4. Abbott RUO assay for pregenomic HBV RNA (pgRNA).
5. Fujirebio HBcrAg (LLOQ 3log10 U/mL).
Results: All participants experiencing HBsAg loss (<0.05 IU/mL)
during therapy (28/52) rapidly became negative with HBsAg Next.
HBsAg <0.005 IU/mL was confirmed at the end of follow-up in 18/18
functional cure and 1/1 virologic control participants with previous
HBsAg <0.05 IU/mL.
A more rapid reduction of S-HBsAg relative to the reduction of other
HBsAg isoforms occurred in 39/40 participants with HBsAg decline
>2 log10 from baseline, consistent with targeting SVPs. At the end of
follow-up, HBsAg isoforms were detectable in 0/18 (FC), 17/19 (VC)
and 15/15 (R) participants. HBsAg IC (relative luminescence units or
RLU) were in the positive range in 30/52 participants at baseline and
at the end of follow-up in 0/18 (FC), 5/19 (VC) and 10/15 (R)
participants.
At baseline, HBV RNA and HBcrAg were present in 42 and 34
participants. HBV RNA loss on therapy occurred in 5/ 14 (FC), 5/16
(VC) and 1/12 (R) participants. HBcrAg < LLOQ on therapy occurred in
5/9 (FC), 7/15 (VC) and 3/10 (R) participants. At the end of follow-up,
both HBV RNA and HBcrAg were > LLOQ in 1/18 (FC), 15/19 (VC) and
13/15 (R) participants.
Conclusion: Functional cure of HBV infection following NAP-based
combination therapy is profound, with HBsAg <0.005 IU/mL and both
HBV RNA and HBcrAg < LLOQ. NEXT negativity and the absence of
HBsAg IC RLUs in the positive range at the end of follow-up in FC
participants suggests efficient reduction in integrated HBV DNA. |
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