3:380,000,000! AIDS cure rate sets new record

Author: Ren Pingsheng

Source: Health World

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3 out of 38,000,000!

This could potentially become the global proportion of HIV-infected individuals who have been cured. Although this figure is only 1/38 million higher than before, it remains undeniably encouraging.

On July 7, local time, the official website of *Science* reported that an HIV-infected individual known as the "São Paulo Patient" appears to have cleared all traces of the HIV virus from their body through a combination of medical treatments.

Screenshot from the official website of *Science*

This 36-year-old male AIDS patient stopped all treatment in March 2019 after undergoing a particularly aggressive regimen combining antiretroviral (ARV) drugs with nicotinamide (vitamin B3). Sixteen months later, HIV was no longer detectable in the patient's blood.

The report stated that most patients who stop HIV treatment after being suppressed by ARV therapy for a period of time see the virus in their bodies rapidly rebound to high levels within weeks. However, in the case of the "São Paulo patient," not only did the HIV virus fail to rebound after treatment was halted—but even the antibody levels dropped to extremely low levels, suggesting that the patient may have cleared HIV-infected cells from both lymph nodes and the gut.

This means that the "San Francisco patient" has become only the third HIV-cured case worldwide—and the first patient cured entirely through medication.

"The 'San Paolo Patient'—An Intriguing Treatment"

The aforementioned research findings were completed by the research team led by Ricard Diaz from the Federal University of São Paulo in Brazil.

Existing research has shown that eliminating HIV is particularly challenging, as the virus integrates its genetic material into human chromosomes, allowing it to enter a dormant state and evade immune surveillance. These silent-infected cells can persist indefinitely, thanks to their stem-cell-like properties, enabling them to replicate themselves. Researchers have proposed several therapeutic strategies aimed at eradicating cells harboring latent HIV infections, yet none of these approaches has proven effective so far.

Díaz's team recruited the "São Paulo patient" and four other HIV patients who had already achieved infection control through ARV therapy in 2015, with the goal of comparing different HIV cell-host exposure strategies.

Researchers had these 5 patients take two additional ARVs on top of the three they were already receiving, hoping to completely eliminate any HIV that might have evaded standard treatment. Afterward, the researchers introduced nicotinamide therapy as an added measure.

Theoretically, nicotinamide can stimulate HIV-infected cells to "wake up" the latent HIV hidden within them. As these cells begin producing new HIV particles, they will either self-destruct or become more vulnerable to attack by the immune system.

After 48 weeks, 5 participants resumed their regular three ARV treatment regimens within 3 years and subsequently discontinued all medication.

It was discovered that HIV rapidly rebounded in four of the individuals, but the "São Paulo patient" has shown no signs of recurrence for 66 weeks, and HIV was not detected in his blood. Furthermore, a more sensitive test involving mixing his blood with HIV-susceptible cells yielded no evidence of newly infected cells.

Interestingly, during the nicotinamide supplementation period, the "São Paulo patient" was the only one among the five individuals who tested positive for HIV in both standard blood tests.

Díaz believes this indicates that the "latent" HIV within infected cells has been activated, ultimately leading to the transient phenomenon of HIV production.

Díaz said, "Perhaps this strategy doesn't work for everyone—maybe it really did eliminate HIV, though we're not entirely sure. Still, I think it's possible."

Only two cases worldwide have been cured.

Since the United States reported its first AIDS case in 1981, approximately 38 million people worldwide have been infected with HIV. Among them, only two cases have ever been cured.

HIV has long been regarded as a 20th-century infectious disease challenge, as the virus features a prolonged latent period and can infiltrate the bone marrow, where hematopoietic stem cells reside—leading to contamination even in newly produced blood. Although effective inhibitors have been developed to keep the infection from progressing further, patients who stop taking these medications risk reactivation of the dormant virus, ultimately causing the disease to worsen again.

Precisely for this reason, bone marrow transplantation has become the only method to eliminate HIV—first, the problematic bone marrow is completely destroyed using intense radiation, and then healthy, virus-free bone marrow is transplanted in its place.

Currently, only two HIV patients worldwide have been successfully cured: the "Berlin Patient" and the "London Patient." Both underwent bone marrow transplants that eliminated HIV from their bodies and provided them with new immune systems capable of fighting off HIV infection. The "Berlin Patient," after receiving a bone marrow transplant in 2006, has remained off antiretroviral therapy for many years—with no sign of HIV reappearing in his system.

However, bone marrow transplantation has a very low matching probability and is an expensive, complex procedure that may cause severe side effects—making it an impractical treatment option for the 38 million HIV carriers worldwide.

This has also brought the treatment case of the "São Paulo patient" into sharp focus. If confirmed, this would mark the first successful case of treatment achieved without bone marrow or stem cell transplantation.

Several uncertain factors

Although the treatment case of the "São Paulo patient" has shown a promising outlook in fighting AIDS, several factors remain uncertain.

First, the "São Paulo patient" has indeed stopped taking ARVs after discontinuing treatment. To confirm this, Diaz plans to check whether the man's blood still contains ARVs.

Another unknown factor is how long after being infected with HIV the "São Paulo patient" began taking ARV treatment.

Research shows that a small group of people who start ARV treatment shortly after becoming infected with HIV are more likely to maintain viral control over a longer period if they stop taking their medication.

"The 'San Paolo Patient' was diagnosed with HIV in October 2012 and began treatment two months later. Like most people living with HIV, he cannot pinpoint exactly when he became infected, though he suspects it may have been in June 2012."

Another issue that requires further investigation is that it remains unclear how nicotinamide reactivates dormant infected cells.

When HIV's genetic material is tightly wrapped around histone proteins in the chromosome, it remains dormant—but to produce viral copies, it must unwind. Diaz pointed out that evidence suggests nicotinamide can trigger this unwinding in distinct ways.

Sharon Lewin, a researcher at the Peter Doherty Institute of Infection and Immunity in Melbourne, Australia, finds the man's HIV antibody response intriguing. However, she emphasizes that this is not a convincing controlled experiment.

Lewin said, "I'd be absolutely thrilled if we could see multiple participants achieve long-term remission in clinical trials. That's precisely where real progress is needed in this field."