The Spleen is a "Sanctuary" for HIV Despite Successful Viral Suppression with cART

David J. Nolan, laboratory director, Bio Info Experts

David J. Nolan

As reported in a recent study published in AIDS Research and Human Retroviruses, the spleen may act as a reservoir for HIV and may contribute to viral persistence, despite the use of combined antiretroviral therapy (cART) and negative results on HIV blood tests.

“There is a lot of prior research focused on lymph nodes as HIV reservoirs during cART, which is not surprising given the number and diversity of immune cells located there,” first study author David J. Nolan, laboratory director, Bio Info Experts, told MD Magazine. “However, spleen and lung tissue have been less frequently studied. The spleen hosts one quarter of the body’s lymphocytes, as well as a diverse population of macrophages, all of which are potential targets of HIV.”

Using single genome sequencing (SGS), investigators collected 50 postmortem tissues from 5 individuals and assessed these samples for HIV nef and env sequences. At death, participants were on cART and presented with no detectable viral load in the blood (<40 HIV copies/mm³ fluid). All participants were members of the National Neurological AIDS Bank program, with the AIDS and Cancer Specimen Resource being used to obtain the tissue samples.

A total of 20 tissues were taken from the brain and 11 of these samples had a positive droplet digital PCR result. Also, a total of 9 liver and kidney tissue sections were evaluated. In total, 18 different tissue types were assayed, and maximum-likelihood phylogenies nef and env demonstrated substantial viral diversity in participants’ spleen, lymph node and lung.

Investigators observed drug resistance mutations among pol sequences in 2 participants (1/3 and 4/5 sequences); however, these mutations were not observed in the 2 other patients. In addition, maximum-likelihood phylogenies nef and env demonstrated substantial viral diversity in participants’ spleen, lymph nodes and lungs.

In some participants, similar or identical viruses appeared to cluster together, which the investigators suggested were representative of “ clonally expanding cells with identical proviral genomes.” Additionally, investigators observed very distinct viruses present on long terminal branches. Among 2 participants, the RNA virus demonstrated similar viral patterns and was scattered with DNA.

Study investigator Dr. Rebecca Rose of Bioinfoexperts explained, “infection of multiple cell types may provide an explanation for the 2 distinct phylogenetic branching patterns found in the sequence populations of the participants, consistent with ongoing evolution in long-lived cells such as macrophages and clonal expansion in T cell populations.” Dr. Rose also published a review article in the same special issue titled "Eradication of HIV from Tissue Reservoirs: Challenges for the Cure" which details current research about HIV tissue reservoirs.

In addition, the researchers suggest that both the persistence and expression of a diverse HIV population among participants who underwent successful cART could be explained by reduced drug penetration of the lymphatic tissues. Based on the results of this study, the spleen appears to be “a prime candidate for an HIV tissue sanctuary and a therapeutic target in HIV cure research.

"These observations are of high importance for HIV cure research because access to tissues from infected humans is rarely accessible,” said Thomas J. Hope, PhD, Editor and Chief of AIDS Research and Human Retroviruses and Professor of Cell and Molecular Biology at the Feinberg School of Medicine at Northwestern University. “The more we understand on how the virus persists, even with potent drug treatment, the more likely that a cure for HIV can be developed.”

REFERENCE

1. Nolan DJ, Rose R, Rodriguez PH, et al. The Spleen Is an HIV-1 Sanctuary During Combined Antiretroviral Therapy. AIDS Res Hum Retroviruses. 2018;34(1):123-125.

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