People who like to “trust their immune system” may take comfort from the fact that someone appears to have eliminated HIV entirely from their body without the use of anti-retroviral drugs. People who understand statistics may pay more attention to the fact this is only the second time this is known to have happened. Scientists hope, however, to apply lessons from this remarkable case to help those without such a super-charged body defense system.
HIV has the capacity to hide from the immune system, and from treatments, in so-called “viral reservoirs”. This means that even if a highly effective treatment program stops, an infected person becomes vulnerable again, leaving most people with HIV needing to take antiretrovirals for the rest of their life.
Two people have been cured of HIV entirely through stem-cell treatment programs that are not considered widely applicable. A third cure has been reported, but remains in dispute. However, last year an individual, known as the San Francisco patient, was found to have eliminated their HIV reservoir simply through having an exceptional immune system. A report in the Annals of Internal Medicine suggests this case was not a one-off or a detection error. Instead, it has occurred a second time.
The new miracle individual is known as the Esperanza Patient, a 30-year-old woman whose partner died of AIDS. She was initially diagnosed with HIV in 2013 and went on antiretroviral therapy (ART) while pregnant in 2019, but was untreated before and afterward. Over four years, Dr Xu Yu of the Massachusetts General Hospital and co-authors sequenced 1.2 billion of the patient's blood cells and 500 million tissue cells. Yu could find no HIV genome in a state to reproduce, even if the immunity that had controlled it were to slip. In particular, the virus was not detected in 150 million CD4+ T cells, usually the prime reservoir. However, one hypermutated viral sequence was found, proving the original infection diagnosis had not been an error.
Elimination of the virus is called a "sterilizing cure”. “These findings, especially with the identification of a second case, indicate there may be an actionable path to a sterilizing cure for people who are not able to do this on their own,” Yu said in a statement. Nevertheless, the paper notes "Absence of evidence for intact HIV-1 proviruses in large numbers of cells is not evidence of absence of HIV-1 infection. A sterilizing cure of HIV-1 can never be empirically proved."
The San Francisco and Esperanza Patients are both extreme examples of “elite controllers”, whose immune systems can prevent HIV from reaching dangerous levels without requiring ART. It is known more run-of-the-mill elite controllers work their magic through particularly potent killer T cells (an appropriate name in current circumstances).
Yu is exploring the possibility of commonality between these two patients' killer T cells. “We are now looking toward the possibility of inducing this kind of immunity in persons on ART through vaccination, with the goal of educating their immune systems to be able to control the virus without ART,” she said.
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