The big “C” for HIV?

March PQ Montly image
By Jonah Sacha, Ph.D., PQ Monthly

When I tell people I work in a laboratory that is developing a vaccine for HIV I often get the following response: “Didn’t we already cure HIV?” The answer is complicated, but for all intents and purposes it is a resounding no. No, we have not found the cure for HIV that millions of HIV+ people are waiting and hoping for. Yes, as of this week there are now two individuals that have been functionally cured of HIV. But these two cases are profoundly extreme, and not directly applicable to the vast majority of people living with HIV/AIDS.

If you’ve recently visited the ARPANET, or what the cool kids like to call “the internet” these days, then you’ve likely seen the news that, for the first time, a toddler has been cured of HIV. Make no mistake, this is an exciting scientific discovery and wonderful news for both the child and mother. But what are the broader implications of this finding for the AIDS epidemic? Is this simply a one-off oddity or is it an approach that can be universally applied to cure others? How excited should we truly be by this?

Before we answer these questions, let’s step back and look at the history of HIV and how “cure” almost became a dirty word in the field of HIV/AIDS research. As my colleague Dr. Burwitz wrote last month in PQ monthly, the AIDS epidemic is now 32 years old, and those 32 years have unfortunately been blighted by constant claims about a cure for HIV. Such claims raise false hope and lead to confusion. Some “cures” were simple miscalculations from well-meaning people, such as the proclamation from the US government that a vaccine would be available within two years following the discovery of HIV as the causative agent of AIDS. Other “cures” were perpetrated by frauds, like the president of Gambia, who claimed he had developed the cure for AIDS. Unfortunately most “cures” have been nothing short of sheer madness with no basis in reality, often targeted to desperate patients. For example, the health minister of South Africa once advocated lemon, beetroot, and garlic as a treatment. And keep in mind that these are only a select few examples of the countless HIV “cures” that have emerged. With this litany of supposed “cures” it’s no wonder then that the “c” word had developed into something of a taboo for HIV researchers. It used to be that if you mentioned cure, you would not be taken seriously as an HIV researcher. But all that changed in 2009 with the announcement of a single amazing case study: The Berlin Patient.

Timothy Brown, aka the Berlin Patient, is the first individual, and until this week the only one, to be functionally cured of HIV. He was diagnosed with HIV in 1995 and for years his antiretroviral medication kept him healthy, but he was diagnosed with leukemia in 2006. After multiple cancer treatments failed, his doctor decided his best chance for survival would be to undergo radiation therapy, which requires a bone marrow (i.e. stem cell) transplant for survival. Here is where it gets interesting. Instead of simply choosing a matched bone marrow donor, his doctor decided he would try something unheard of; he would try to cure his patient of both cancer and HIV. To this end, he selected a bone marrow donor who was a match and also had a rare genetic mutation, which provides natural resistance to HIV. Remarkably, this approach worked and Mr. Brown became the first verified individual to be functionally cured.

While the case of Mr. Brown is incredible, it’s important to temper excitement and realize what a profoundly extreme example this truly is. Bone marrow transplants are a major clinical procedure with mortality rates as high as 50 percent. Indeed, other attempts at this approach have failed, due to the harshness of the transplant procedure and lack of suitable bone marrow donors (Mr. Brown was amazingly lucky — one suitable donor was identified out of over 13 million!). Furthermore, it’s important to note that this is a “functional cure,” which means the virus is currently undetectable but may still be present. HIV, unfortunately, has a nasty habit of hiding out in our in DNA, only to reemerge years later. Indeed, unconfirmed reports have recently surfaced that HIV is again detectable in samples from Mr. Brown. Only time will tell whether he is well and truly cured.

In any case, Mr. Brown is no longer alone as the only individual cured of HIV. Just this week, he was joined by a two year old toddler from Mississippi. In contrast to Mr. Brown, the child did not receive a bone marrow transplant. Instead, she received triple antiretroviral drug therapy for 18 months beginning at 30 hours from birth (her mom was HIV-positive). Amazingly, HIV is not detectable in the child, despite the fact that she stopped taking drugs at 18 months of age and is now two and a half years old. However, similar to the case of Mr. Brown, excitement must be tempered. While immediate antiretroviral drug therapy is key to this exciting case, it is not applicable to the overwhelming majority of new HIV infections. New HIV patients do not often learn they are HIV-positive for weeks or months after infection. (HIV is called a lentivirus, which in latin means “slow virus,” because of the long period of time they do not cause overt disease following infection.) By then, it is too late, as HIV has established its DNA hideout.

So, to answer the questions posed at the beginning of this blog, this is an exciting finding, but unfortunately not one that can be applied across the board to cure other HIV-positive patients. However, the number of individuals that have been functionally cured has now doubled and that is reason for optimism. It means that the “c” word is no longer a taboo in HIV research. It means that it is possible to cure HIV. It means that we have to get back to work!