Talk of an “HIV cure” makes for excellent click-baity headlines. But although monumental breakthroughs continue to keep HIV-positive people, researchers, advocates, and allies optimistic about eradicating the virus, let’s not confuse good news with fantasy half-truths.
In light of the recent reports about a man living with HIV being "cured," it's important to clarify a few things.
Media outlets have latched on to the word "cure" and have spread optimism to the highest office in the land, reaching President Donald Trump, who seemingly took credit for the discovery in a tweet, while quoting The New York Times, a publication he consistently calls "fake news."
“HIV Is Cured In 2nd Patient, Doctors Report.” @nytimes Such great news for so many. Tremendous progress being made!
— Donald J. Trump (@realDonaldTrump) March 5, 2019
The president's statement is ironic and hypocritical at the same time.
In 2017, shortly after the Trump administration came on board, he unceremoniously fired all of the AIDS Council members, and last December he halted a study that would use fetal tissue to discover a cure for HIV, showing that he's constantly fighting against finding a cure. But in his State of the Union speech, he seemed to set out a plan for eradicating HIV by 2030.
The truth is, HIV activists and advocates really do think we can eradicate HIV in the U.S. But 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 (undetectable equals untransmittable, aka the fact that when HIV-positive people are on treatment and virally suppressed, they cannot transmit HIV to others).
But the plan that the Trump administration has proposed is likely to fail, for numerous reasons.
This week, it was reported that a man living in London who’d previously been HIV-positive was showing no trace of the virus after more than 18 months since coming off antiretroviral drugs. That this feat — while notable — is being hyped as a cure (and that if it was, it would mean we could cure HIV in everyone) 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 so that 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, and it is much rarer among Native Americans, Asians, and Africans. A 2005 report indicated that 1 percent of people descended from Northern Europe are virtually immune to HIV.
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 man in London, now dubbed 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 remains free of the virus. There have been other people "cured" before — and in every case except for Brown's, their HIV has rebounded, usually with a few years. Eighteen months HIV-free, while remarkable, is simply not proof that one's HIV will remain in remission.
First, let me explain the difference between a functional cure and an eradication cure. For doctors to call an HIV-positive person "functionally cured," they need to make certain that levels of HIV are undetectable in the bloodstream. To some extent, this is accomplished today with antiretrovirals, HIV treatment medications that suppress the virus to such low levels that it is no longer detectable in the bloodstream and no longer transmittable to others. This idea is at the heart of U=U, which has been supported by hundreds of doctors, advocates, organizations, and governmental agencies like the U.S. Centers for Disease Control and Prevention.
Now, an ideal functional cure would be for people living with HIV to get to a point where daily drugs are no longer needed to keep the virus suppressed. We are getting there, slowly, thanks to multiple vaccines currently being studied and milestones in the pharmaceutical landscape, leading to long-acting HIV medications (pills and shots) coming to the market in the next few years.
But even in the best-case scenarios, HIV researchers admit that functional cures will likely last no more than a decade at a time. And essentially, a functional cure means that 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 eradication of the virus from the body. 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 isn't 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.”
HIV reservoirs are found throughout the body, though the most common are in T cells, and they are the biggest barriers to eradicating HIV.
Despite a person being on medication and undetectable, HIV can remain dormant in reservoirs. 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. And then you're back to square one.
Depending on the person’s immune system and genetics, HIV might take days, weeks, months, and in recent cases, years to rebound after getting off antiretrovirals. This window is referred to as “sustained HIV remission."
In every case, the virus always bounces back. The question is never if, but when?
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 parallels in that they both received bone marrow stem cell transplants from a donor with the Delta32 mutation. The procedure itself is so risky that only 38 people in the world have received it, 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. The major difference is that Brown suffered through this condition for months and was even placed in an induced coma at one point, and nearly died.
However, the London Patient didn’t seem to suffer nearly as much as Brown did after the transplant. In fact, his recovery was more “in line with current standards for transplant patients,” according to reports.
“[Brown] was really beaten up by the whole procedure,” reflected Dr. Steven Deeks, an AIDS 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.”
The London Patient hasn’t taken antiretroviral drugs since September 2017 and is still in remission, which makes him the second patient since Brown to remain virally suppressed for over a year after stopping treatment.
Scientists have 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. While the two men remained in remission after the procedure, 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.) Still, the case provided keen insight into what might trigger a rebound in the first place.
Also that year, an HIV-positive 12-year-old boy named Eric Blue 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 this 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.)
Numerous cases throughout the years had similar ends. In most successful cases, early treatment showed to be a key factor in long-term remission.
For example, in 2017 a South African child was found to have suppressed HIV without any medications for over eight years due to early treatment that was given immediately after birth. When the child turned 9, scientists discovered a small reservoir in the child's immune cells, but no evidence of it replicating.
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 is 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.
In regards to the London Patient, it’s too early to know what his ultimate contribution will be to the development of a cure. It's certainly too early to call him cured.