# Adherence and Intracellular Pharmacology of Tenofovir and HBV Suppression in People with HBV/HIV Coinfection

> **NIH NIH R21** · UNIVERSITY OF FLORIDA · 2021 · $185,275

## Abstract

Program Director/Principal Investigator (Last, First, Middle):
ABSTRACT
Hepatitis B virus (HBV) and human immunodeficiency virus (HIV) share common modes of transmission. As a
result, people with HIV (PWH) are disproportionately affected by chronic HBV. Globally, an estimated 2.7
million PWH have HBV coinfection. In high endemic areas such as Africa, up to 25% of PWH also have HBV
coinfection. In the United States, 5 to 10% of PWH have HBV coinfection. Persons with HBV/HIV coinfection
have a higher risk for liver cirrhosis, hepatocellular carcinoma (HCC) and liver related death compared to those
without HIV. The risk of life-threatening complications due to HBV is strongly related to the level of viral
replication. Thus, the goal of treatment is to achieve sustained virologic suppression. In HBV/HIV co-infected
patients, tenofovir (TFV) disoproxil fumarate (TDF) or TFV alafenamide (TAF) plus emtricitabine (FTC) or
lamivudine (3TC) is recommended as essential components of antiretroviral therapy (ART). Tenofovir is the
most potent nucleotide analogue for HBV treatment. While TFV resistance leading to suboptimal therapy is
extremely rare up to 8 years of use, incomplete suppression of HBV replication on TDF-based therapy is
common. The reason(s) why some HBV/HIV co-infected individuals fail to achieve undetectable HBV viremia
despite full suppression of HIV on TDF-based ART is also unknown. We propose that higher levels of ART
adherence and/or drug exposure at the site of viral replication is needed for HBV suppression than for HIV.
The efficacy of TFV is dependent on intracellular concentrations of the active phosphate anabolite, TFV
diphosphate (TFVdp). We hypothesize that insufficient intracellular TFVdp concentrations will be the central
mechanism associated with HBV non-suppression, and covariates of intracellular TFVdp pharmacokinetics
(PK) would predict risk of unsuppressed HBV. The primary goal of this project is to determine the contribution
of TFVdp PK and/or medication adherence to suboptimal HBV suppression on TDF-based ART. We will
accomplish our goal through the following specific aims: 1.) Determine the relationship between TFVdp
concentrations in DBS and PBMCs and HBV suppression in HIV/HBV co-infected patients on TDF-containing
ART; 2.) Determine demographic and genetic covariates of intracellular TFVdp concentration and HBV
virologic suppression in HIV/HBV co-infected patients on TDF-containing ART. Defining the covariates of TFV
PK and virologic response (PK/PD) for HBV could inform individualized strategies to optimize HBV treatment
response. Discoveries from this project could form the basis for developing and testing adherence-based or
genotype-guided interventions to optimize HBV outcomes in HIV co-infected patients.
OMB No. 0925-0001/0002 (Rev. 01/18 Approved Through 03/31/2020) Page Continuation Format Page

## Key facts

- **NIH application ID:** 10136513
- **Project number:** 5R21AI147384-02
- **Recipient organization:** UNIVERSITY OF FLORIDA
- **Principal Investigator:** Awewura Jacob Kwara
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $185,275
- **Award type:** 5
- **Project period:** 2020-04-01 → 2024-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10136513

## Citation

> US National Institutes of Health, RePORTER application 10136513, Adherence and Intracellular Pharmacology of Tenofovir and HBV Suppression in People with HBV/HIV Coinfection (5R21AI147384-02). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10136513. Licensed CC0.

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