Liver May Be Reservoir for HIV DNA in Patients With HBV Coinfection on ART

Detectable HIV RNA was found in liver samples obtained from patients with HIV and hepatitis B coinfection receiving ART, including in both hepatocytes and CD4+ T-cells.

Results of a study published in eBioMedicine found that the liver may be a potential reservoir for HIV DNA among individuals with HIV infection receiving antiretroviral therapy (ART).

Data for this prospective longitudinal cohort study were sourced from the HIV-Netherlands-Australia-Thai Research Collaboration (HIV-NAT). Researchers assessed blood and liver specimens obtained from a subgroup of patients (N=18) with HIV and hepatitis B virus (HBV) coinfection prior to and following ART initiation. The presence and levels of HIV and HBV DNA and RNA were evaluated using quantitative polymerase chain reaction testing and RNA/DNAscope, and plasma ART levels were quantified via mass spectroscopy.

Prior to ART initiation, the median patient age was 32.5 (range, 21.3-44.6) years, 94.4% were men, and 66.7% consumed alcohol less than once monthly or never. In addition, 55.5% of patients had mild liver fibrosis (grade, F0-F2), 16.7% had moderate liver fibrosis (grade, F3), and 11.1% had severe liver fibrosis (grade, F4).

After a median of 3.4 years following ART initiation, there were no patients with severe liver fibrosis. During ART, significant decreases in aspartate transaminase (P =.0394) and increases in alkaline phosphatase (P =.0086) and gamma-glutamyl transferase (P =.0248) were observed among the patients, however, levels for each remained within reference ranges.

Analysis of blood samples indicated HIV DNA decreased from 1439 to 166 copies/106 cells (P <.0001) after ART initiation. Prior to ART initiation, 53% and 47% of the patients had detectable HIV DNA and RNA in the liver, respectively. At follow-up, however, no patient had detectable HIV RNA in the liver (P <.01), though 39% had detectable HIV DNA.

Further work is needed to understand the liver as a reservoir for HIV infection other PWH…

To confirm this finding, the researchers used amplicon sequencing to evaluate 3 liver biopsy specimens obtained from patients with the highest detectable HIV DNA levels. Each specimen differed in sequence by 1 or more nucleotides and the sequences clustered away from the subtype B consensus sequence, suggesting this finding was likely not due to laboratory contamination.

Further analysis by DNAscope showed a low-level of detectable HIV DNA in 33% of the liver samples. In liver tissue, HIV DNA was detected in CD4+ T-cells and hepatocytes.

Both amplicon sequencing and DNAscope analyses indicated that 61% of the patients had detectable HIV DNA in the liver after a minimum of 2 years on ART.

Stratified by type of ART, the levels of HIV DNA in plasma and liver tissue samples were similar among patients receiving emtricitabine (P =.3180). However, levels of HIV DNA were significantly higher in liver tissue samples compared with levels observed in plasma samples among patients receiving tenofovir disoproxil fumarate and efavirenz.

Fibrosis at baseline was found to correlate with the presence of HIV DNA in liver tissue samples obtained at follow-up after ART initiation (r, 0.5221).

The major limitation of this study was the small sample size. In addition, the sensitivity for the detection of HIV DNA in the liver was significantly decreased due to the limited number of cells obtained from a standard liver biopsy.

According to the researchers, “Further work is needed to understand the liver as a reservoir for HIV infection other PWH [patients with HIV infection]…”

Disclosure: Multiple authors declared affiliations with industry. Please see the original reference for a full list of disclosures.


Zerbato JM, Avihingsanon A, Singh KP, et al. HIV DNA persists in hepatocytes in people with HIV-hepatitis B co-infection on antiretroviral therapy. EBioMedicine. 2022;87:104391. doi:10.1016/j.ebiom.2022.104391