Hepatitis B Replication Persistent in HIV Coinfection Treated With Tenofovir-Based ART

Although hepatitis B replication commonly persists in patients with HIV coinfection receiving tenofovir-based ART, most patients eventually achieve suppression.

More than 25% of patients coinfected with virologically-suppressed HIV and chronic hepatitis B virus (HBV) experienced an HBV replication event after 2 years of tenofovir-based antiretroviral therapy (ART), according to results of a study published in Clinical Infectious Diseases.

Data for this longitudinal, observational cohort study were sourced from the Swiss HIV Cohort Study. The subset of study patients (N=222) with chronic HBV and HIV coinfection who had received at least 4 years of tenofovir-based ART prior to October 2019 were evaluated for HBV replication events. Patients self-reported ART adherence using standardized questionnaires. Chronic HBV was defined as 2 reactive hepatitis B surface antigen test results more than 6 months apart. Persistent HBV viremia was defined as an HBV viral load of at least 20 IU/mL, and suboptimal ART adherence was defined as an HIV viral load of at least 200 copies/mL. The primary outcome was HBV suppression (<20 IU/mL) at 2 years and at the final follow-up visit. Risk factors for HBV replication were evaluated using multivariable logistic regression.

Among patients included in the analysis, the median age was 41 (IQR, 36-47) years, 19% were women, 21% had sub-Saharan African ancestry, 73% had a previous AIDS-defining condition, and 40% were naive to ART prior to tenofovir-based ART initiation.

At the start of tenofovir-based ART, 47% of the patients had CD4 counts of more than 350 cells/µL, 59% had high-level HBV viremia (>2000 IU/mL), 26% low-level viremia (range, 20-2000 IU/mL), and 15% were suppressed. In addition, 14% of the patients had hepatitis D virus (HDV) coinfection, of whom 67% had replicating HDV at baseline.

After 2 years of tenofovir-based ART, HBV viremia was noted in 27% of the patients, among whom 10% had high-level viremia. Stratified by HBV viremia level, the percentage of patients with adequate tenofovir-based ART adherence was higher among those without HBV viremia vs those with HBV viremia (98% vs 92%; P =.03).

The risk for persistent hepatitis B viremia at 2 years was found to be associated with high-level HBV viremia at baseline (odds ratio [OR], 1.38; 95% CI, 1.20-1.57). Further analysis showed that this risk was decreased among patients who self-reported adequate adherence to tenofovir-based ART (OR, 0.04; 95% CI, 0.01-0.33), those with HDV coinfection (OR, 0.07; 95% CI, 0.01-0.59), and those with CD4 counts higher than 350 cells/µL at baseline (OR, 0.41; 95% CI, 0.19-0.90).

[I]t will be crucial to understand why a minority of individuals do not reach suppression, including by conducting genome-wide HBV sequencing analyses and immunological studies.

At the latest follow-up visit (median follow-up, 8.4 years), HBV replication was noted in 32 (16%) patients. There were also 61 patients with HBV replication at 2 years, 14 (23%) of whom had persistent viremia. Of these patients, 86% had high-level viremia at tenofovir-based ART initiation, 79% were men, 57% were previously diagnosed with an AIDS-defining condition, 50% had received lamivudine or emtricitabine-based ART prior to baseline, and 21% had sub-Saharan African ancestry.

Among 161 patients with HBV suppression at 2 years, 18 (11%) had incident HBV replication at the latest follow-up visit.

This study may have been limited by its reliance on self-reported data to determine ART adherence.

For future studies, “it will be crucial to understand why a minority of individuals do not reach suppression, including by conducting genome-wide HBV sequencing analyses and immunological studies,” the researchers concluded.

Disclosure: One author declared affiliations with industry. Please refer to the original article for a full list of disclosures.


Hofmann E, Surial B, Boillat-Blanco N, et al. HBV replication during tenofovir therapy is frequent in HIV/HBV-coinfection. Clin Infect Dis. Published online October 15, 2022. doi:10.1093/cid/ciac823