The study aims to assess safety and tolerability of oral toll-like receptor (TLR) 8 agonist Selgantolimod (SLGN) administered for 24 weeks in participants with both CHB and HIV who have been receiving suppressive antiviral therapy for both viruses for ≥5 years and have qHBsAg level >1000 (3 log10) IU/mL at screening. The study will also evaluate if TLR8 stimulation with SLGN will reduce hepatitis B surface antigen (HBsAg) titers in the blood.

A5394 is a phase II, double-blinded, placebo-controlled trial. Forty-eight study participants will be randomized 3:1 to receive SLGN or its placebo (36 active and 12 placebo), and randomization will be stratified by HBeAg status. One-half of the study participants will be HBeAg positive (n=24) at screening, and the other half will be HBeAg negative (n=24). All participants will remain on their non-study-provided antiviral therapy throughout the study.

Inclusion Criteria:

1. HIV-1 infection
2. Effective antiviral therapy for HIV (ART) and HBV that includes TDF, TAF, TDF/FTC, TDF/3TC (tenofovir disoproxil fumarate plus lamivudine), TAF/FTC, or entecavir (ETV), for ≥5 years immediately prior to study entry. ART is defined as including a minimum of two anti-HIV antivirals.
3. CD4+ cell count ≥350 cells/mm3
4. HIV-1 RNA <50 copies/mL measured on at least two occasions at least 12 weeks apart, with no documented value >200 copies/mL, over the 12 months prior to study entry.
5. Positive or negative HBeAg
6. Negative anti-HDV
7. Current CHB infection
8. HBV DNA level <50 IU/mL measured on at least two occasions at least 12 weeks apart, with no documented value ≥50 IU/mL, over the 12 months prior to study entry.
9. Quantitative HBsAg >1000 IU/mL
10. Hepatitis C virus (HCV) antibody negative, or if the participant is HCV antibody positive, an undetectable HCV RNA.
11. Participants age ≥18 years and ≤70 years at study entry
12. Participants must agree to stay on an effective antiviral therapy for HIV (ART) and HBV throughout the study.

Exclusion Criteria:

1. Receipt of treatment for HCV within 24 weeks prior to study entry
2. Evidence of advanced fibrosis or cirrhosis (Metavir ≥F3 or equivalent).
3. Current or prior history of clinical hepatic decompensation (e.g., ascites, encephalopathy, or variceal hemorrhage)
4. History of HCC or cholangiocarcinoma
5. Malignancy within 5 years prior to study entry. NOTE: A history of non-melanoma skin cancer (e.g., basal cell carcinoma or squamous cell skin cancer) is not exclusionary.
6. History of solid organ transplantation
7. Presence of any active or acute AIDS-defining opportunistic infections within 60 days prior to study entry
8. History of uveitis or posterior synechiae
9. Breastfeeding

Individual participant data that underlie results in the publication, after deidentification

Beginning 3 months following publication and available throughout period of funding of the AIDS Clinical Trials Group by NIH

With whom? Researchers who provide a methodologically sound proposal for use of the data that is approved by the AIDS Clinical Trials Group. For what types of analyses? To achieve aims in the proposal approved by the AIDS Clinical Trials Group. By what mechanism will data be made available? Researchers may submit a request for access to data using the AIDS Clinical Trials Group "Data Request" form at: https://actgnetwork.org/submit-a-proposal/. Researchers of approved proposals will need to sign an AIDS Clinical Trials Group Data Use Agreement before receiving the data