HIV Replication Unlikely to Occur in Liver Cells After Long-Term Antiretroviral Therapy

Study examines the role of liver macrophages as a long-lived HIV-1 cellular reservoir.

Detectable HIV-1 found in liver immune cells, known as macrophages, are unlikely to reactivate infection on their own in individuals with HIV on long-term antiretroviral therapy (ART), according to a new study.

ART effectively suppresses the replication of the virus in patients who adhere to treatment. However, if therapy is discontinued, HIV replication can be activated and spread in the body due to viral reservoirs that are formed during infection. These persisting reservoirs remain a barrier to curing the disease.

The proof-of-principle study, published in the Journal of Clinical Investigation, aimed to determine whether liver macrophages were a true source of infection-capable HIV-1 reservoirs after ART.

“Tissue macrophages are abundant, long-lived, and susceptible to HIV-1 infection; however, their role as a long-lived HIV-1 cellular reservoir has been difficult to address in humans,” the researchers wrote in the study.

The researchers took liver tissue samples from 9 individuals with HIV-1, 7 of whom underwent liver transplantation at the Johns Hopkins Hospital, and would otherwise have had their livers discarded. Eight of these individuals were on ART for periods ranging from 8 to 140 months.

“Our study was the first, to our knowledge, in which purified liver tissue macrophages from HIV-1 infected people taking ART directly tested the idea that tissue macrophages are a long-livtd active HIV-1 reservoir,” study author Ashwin Balagopal, MD, an associate professor in the Division of Infectious Diseases at the Johns Hopkins University School of Medicine.

The researchers measured HIV-1 containing T cells and separated out the liver macrophages, finding HIV-1 to be present in the macrophages even after exposure to long-term ART. However, when the researchers attempted to stimulate the virus in the liver macrophages, the HIV-1 reservoirs were not robust enough to restart infection.

Based on the study findings, the researchers indicated that defective or inert HIV-1 can remain in the liver macrophages for up to 10 years without functioning as an HIV-1 reservoir. To search for a potential cure for the disease, the researchers suggested shifting focus more to other cell types that are more likely to serve as active reservoirs.

Although the results provide a better understanding of the role of non-T cells as HIV-1 reservoirs, more research is needed to determine the functional significance of the inert HIV-infected liver macrophages, the researchers noted.

“To find a comprehensive HIV-1 cure, it’s important to identify all of the relevant HIV-1 reservoirs in the body, since it’s possible that the virus hides in the DNA of numerous cell types and each may require different strategies to get a cure,” Dr Balagopal concluded.

References

Kandathil AJ, Sugawara S, Goyal A, et al. No recovery of replication-competent HIV-1 from human liver macrophages. The Journal of Clinical Investigation. 2018. Doi: 10.1172/JCI121678.

No “Reservoir”: Detectable HIV-1 in Treated Human Liver Cells Found to Be Inert [news release]. Johns Hopkins’ website. https://www.hopkinsmedicine.org/news/newsroom/news-releases/no-reservoir-detectable-hiv-1-in-treated-human-liver-cells-found-to-be-inert. Accessed October 1, 2018.