Researchers have discovered that clonally expanded human immunodeficiency virus (HIV)-infected cells can persist and produce new virus over many years in patients receiving combination antiretroviral therapy (cART). Thus, any cure for HIV infection will have to attack these cells to permanently clear the virus, according to an article posted on the Medical Xpress website. The new study was published in the Proceedings of the National Academy of Science.
Although medical research has resulted in the transformation of HIV infection from a terminal disease to a manageable condition, no vaccine, drug, or therapy can permanently cure an infected patient. Failure to adhere to a strict regimen of combination antiretroviral drugs invariably results in the recurrence of detectable HIV. One reason is the ability of latent virus to persist in cells and re-emerge in response to imperfectly understood stimuli, the Medical Xpress article says.
In the new study, published in the Proceedings of the National Academy of Sciences, researchers at the National Institutes of Health, the National Cancer Institute, and other centers have established for the first time that reservoirs of infectious HIV-1 persist in CD4+ T cells that are clonally expanded––that is, a population of many cells that have been produced by a single cell. These T-cell clones contain active virus that can begin to proliferate after cART has been stopped.
The results were derived from the study of a single HIV-positive African-American patient who was diagnosed with the virus in 2000. The researchers conducted virological, immunological, and anatomical analyses of the patient from the time that he began cART until he died 13 years later from cancer. Before the publication of the study, it was unknown whether the identical viruses found in the blood cells of HIV patients were infectious.
“This result shows that cells containing replication-competent HIV-1 proviruses can clonally expand and persist in vivo, presenting a challenge for achieving a cure of HIV infection,” the researchers state in their article.
It is not known which CD4 subtypes contain viable HIV (most latent reservoirs do not contain replication-competent virus), and the researchers note that further study is required to establish the mechanisms of HIV production during persistence and clonal expansion. Nor does the present study establish whether these expansions are the result of homeostatic proliferation or a response to an antigen, the researchers note.
“To develop successful curative strategies, a better understanding is needed of the fraction of the replication-competent reservoir that is composed of clonally expanded cells and how to specifically target and eliminate them,” they conclude.