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HIV Remission Is Not a Cure, Let's Be Clear

Cure

Earlier this year, headlines trumpeted the “cure” of a London man who’d previously been HIV-positive but is currently showing no trace of the virus after more than 18 months off antiretroviral drugs. That this feat — while notable — was hyped as a cure just shows how little the general public understands HIV and cure research.

The unidentified man had a bone marrow stem cell transplant from a donor with a rare genetic mutation resistant to HIV called Delta32 — a mutation that prevents a protein called CCR5 from rising to the surface of T cells where HIV can latch on to it. When CCR5 isn’t there to latch on to the virus, HIV is inadvertently unwelcome and thus closed off from infecting cells.

Scientists believe this genetic mutation has been inherited from ancestors who survived the massive bubonic plague outbreaks in Europe centuries ago. Perhaps 1 percent of Caucasians have the mutation, making them virtually immune to HIV. It is much rarer among Native Americans, Asians, and Africans.

Delta32 and CCR5 first became the talk of the town in HIV research nearly 12 years ago when Timothy Ray Brown (dubbed the “Berlin Patient”) was cleared of HIV after receiving stem cell transplants from a donor with the Delta32 mutation to treat cancer (as did the “London Patient”).

According to many reports, Brown’s virus has not returned, which makes him the longest functionally HIV-cured person that we know of. This is all great news, but let’s not forget some inconvenient facts.

For example, as of 2017, an estimated 36.9 million people were living with HIV — and yet Brown is the only individual who has remained free of the virus for a decade or more. And the treatment in both Brown’s and the London Patient’s cases is invasive and potentially lethal, which is why it’s only been utilized in cases where the person is fighting terminal cancer.

Other people have been “cured” before — and in every case except for Brown’s, their HIV has rebounded, usually within a few years. Eighteen months HIV-free, while remarkable, is simply not proof that one’s HIV will remain in remission.

There’s also a difference between what is called a “functional cure” and an “eradication cure.” For doctors to claim an HIV-positive person functionally cured, they need to make certain that levels of HIV are undetectable in the bloodstream and those levels don’t rebound when that person stops taking antiretroviral medication.

Today’s HIV treatment medications can suppress the virus to such low levels that it is no longer detectable in the bloodstream, and is no longer transmittable to others. This fact is at the heart of the statement undetectable equals untransmittable (U=U), which is now supported by reams of research and affirmed by hundreds of doctors, advocates, organizations, and governmental agencies like the U.S. Centers for Disease Control and Prevention.

We’re closing in on a time where daily drugs are no longer needed to keep the virus suppressed. Several long-acting HIV medications are in the pipeline and should be available in the next few years. And promising studies involving vaccines suggest they could be used to keep HIV virally suppressed for years at a time.

Even in the best-case scenarios, researchers admit that functional cures will likely last no more than a decade. A functional cure means the virus is still in the person’s system, hiding in what are known as HIV reservoirs, from which it can rebound at any point once treatment is stopped.

An eradication cure is different. It would entail the complete elimination of the virus from the body altogether. That means getting rid of every ounce of active (and dormant) HIV from the blood, organs, and reservoirs. And we’re not there yet. To be frank — we’re not even close. In fact, as top researchers told Plus in 2017, full eradication is no longer the focus of most research.

“We’ve not given up entirely on the notion of eradication,” Dr. Warner Greene, director of Gladstone Institute of Virology and Immunology and a leading cure researcher, told us. “But I think where the successes and the gains are being made is around the area of being able to reduce and control the virus.”

Despite a person being on medication and undetectable, HIV can remain dormant in reservoirs and they are the biggest barriers to eradicating HIV. Once a person gets off treatment, these cells can reawaken and start multiplying all over again, which allows viral loads to rebound and become detectable again. The period of time between when treatment stops and the virus rebounds is referred to as “sustained HIV remission.”

Ravindra Gupta, a professor and HIV biologist who co-led a team of doctors treating the London Patient, has specifically referred to him as “in remission,” explaining to Reuters, “It’s too early to say he’s cured.”

The Berlin and London patients share similar parallels in that they both received bone marrow stem cell transplants from donors with the Delta32 mutation. The procedure itself is so risky that only 38 people in the world have received them, according to The New York Times. The London Patient was number 36.

Both the Berlin and London patients also suffered through a period of “graft-versus-host” disease, which is basically a condition whereby the donor’s immune cells attack the recipient’s immune cells on contact. Brown reportedly suffered through this condition for months and was even placed in an induced coma at one point. He nearly died.

“[Brown] was really beaten up by the whole procedure,” reflected Dr. Steven Deeks, an HIV expert who has treated Brown, to The Times. “And so we’ve always wondered whether all that conditioning, a massive amount of destruction to his immune system, explained why Timothy was cured but no one else [was].”

One hopeful sign with the London Patient is that his recovery from the procedure was reported as being more like that experienced by transplant patients.

Having not taken antiretroviral drugs since September 2017 and still in remission, the London Patient is now the second person since Brown to remain virally suppressed following the procedure for over a year after stopping HIV treatment.

Scientists have previously tried to repeat Brown’s success with no luck.

In 2012, researchers reported on cases of two HIV-positive men who’d also received stem cell transplants and went into remission after the procedure — but their HIV rebounded months later. (In both cases, their donors did not have the Delta32 mutation.)

The following year, a baby from Mississippi who was born with HIV also appeared to have been cured. Scientists credited early HIV treatment as a reason why the baby remained undetectable for 27 months before rebounding. (In that case the child had not been consistently followed by researchers, so its medical history is not as well documented as that of the adult patients. And the length of time in remission isn’t considered reliable.)

Also that year, an HIV-positive 12-year-old from Minnesota received the same stem cell transplant as Brown and the London Patient. Sadly, he died of graft-versus-host disease before scientists were able to test whether or not the procedure worked in suppressing his HIV. (And it’s sort of moot as to whether he was cured of HIV, if the cure itself proved deadly. In fact, researchers have previously noted the risk of death is one reason they don’t recommend these potentially curative treatments more broadly, especially given that people with HIV can live long and healthy lives with current treatment.)

All this being said, optimism is still important — and warranted. HIV is being controlled better than ever, and someone diagnosed with HIV today has nearly the same life expectancy as their HIV-negative peers.

There has been great progress toward longer-lasting treatments and even functional cures. But we shouldn’t confuse that with the fantasy that an eradication cure is just around the corner or could be widely available to the public within a few years. Those things simply are not the case.

But the truth is, HIV activists and advocates really do think we can eradicate HIV in the U.S. It’s just that when they talk about “eradicating” HIV or “ending AIDS,” they aren’t speaking about a hypothetical cure. Instead, they are talking about a well-funded approach to eliminating HIV transmission via proven methods like access to PrEP and embracing the true potential behind U=U. If more people know their status, HIV-negative people at risk take PrEP, and people living with HIV have their viral loads suppressed, we can stop the epidemic.

Then researchers can focus on making sure those with HIV can live long and healthy lives.

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