Is Natural Long-Term HIV Suppression Possible for More Patients?

Typically, people with HIV must rely on antiretroviral therapy to keep their viral levels down. However, a tiny handful of people have a natural ability to keep their viral load low without medication. Investigators at Johns Hopkins University School of Medicine recently published a paper highlighting their findings after studying 2 patients with HIV who have the rare ability to achieve viral suppression in the absence of antiretroviral therapy.

One patient, termed an “elite suppressor,” carries the genetic marker HLA-B*57. This gene allows him to maintain low viral levels without ever having taken antiretroviral therapy. The second patient, termed a “post-treatment controller,” did take antiretroviral therapy for several years but has not done so for the past decade and a half. He has no genetic markers that offer any natural protection against HIV, yet he too is able to keep his viral levels at an undetectable level. Both patients are middle-aged African-American men.

In the normal course of the disease, HIV invades immune cells called CD4+ T cells, where it replicates and eventually enters the bloodstream. Another type of immune cell, the CD8+ T cell, can kill off the infected CD4+ T cells if it’s early enough in the process; however, most CD8+ T cells are overpowered by the sheer volume of CD4+ T cells, and fail to stop the cells’ replication. As the cells replicate, they tend to mutate, meaning that HIV cells found in a single patient’s body today are likely to be different than HIV cells found in his or her body several years ago.

The investigators, however, made a different discovery when examining the HIV cells culled from the patients over a period of several years. After studying the virus isolated from the post-treatment controller in 2010 and again in 2017 (when the virus was tested 2 separate times, 6 months apart), the team found that the cells were nearly identical 7 years later. And after comparing cells isolated from the elite suppressor in 2017 with those isolated from him in 2013, the investigators again discovered that all of the virus cells were nearly identical.

The implication of the near-identical cells detected, even years later, is that the virus actually cloned itself. The cloned viruses formed a reservoir in CD4+ T cells, never entering the bloodstream. The investigators hypothesize that, when it comes to these patients, their own CD8+ T cells could be major players in keeping their viral loads under control. When the research team culled CD8+ T cells from the 2 patients and combined them with their own HIV-infected CD4+ T cells, the virus remained suppressed. When the team combined other peoples’ CD8+ T cells with the 2 patients’ HIV-infected CD4+ T cells, however, the low viral levels could not be maintained.

“CD8+ T cells from both subjects were able to inhibit replication of their own virus in their own CD4+ T cells,” Joel N. Blankson, MD, PhD, professor of medicine at the Johns Hopkins University School of Medicine and an author of the study, told Contagion®. “The elite suppressor had the genetic marker HLA-B*57, which is associated with strong HIV-specific CD8+ T cell responses in some patients. We don’t know why the post-treatment controller had strong HIV-specific CD8+ T cell responses to his own virus but not to laboratory isolates.”

Although other studies have cast doubt on the suppressive role of the CD8+ T cell, those studies differed from the current one by not isolating the HIV virus from the same subjects whose CD8+ T cell function was being examined, Rebecca T. Veenhuis, PhD, a research associate also at Johns Hopkins University School of Medicine and a coauthor of the study told Contagion®.

“If our finding holds true for other post-treatment controllers, then it suggests that this is the mechanism of control. Developing CD8+ T cell vaccines alone with treating patients early in infection could possibly lead to extended periods of post-treatment control in some subjects,” she concluded.