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Ever since human immunodeficiency virus (HIV) was first detected in the 1980s, people have been asking one question above all others: When will there be a cure?
For many, the 1980s was a terrifying time. In 1981, cases of rare infections and cancers began showing up in men who have sex with men (MSM) in urban centers in the United States. It then took two years before the cause was determined to be a virus that affected the immune system. And it took another three years for that virus to be named HIV. Meanwhile, countless numbers of young people who had previously been healthy were becoming severely ill and dying.
For several agonizing years, not only was a cure out of reach—there wasn’t even any treatment for HIV. Uncertainty regarding exactly how the virus spread caused many to be fearful of coming into contact with HIV-positive individuals. And even when healthcare providers were willing to engage, no available antiretroviral medications existed.
Finally, on March 19, 1987, the Food and Drug Administration (FDA) approved the drug AZT as a treatment for HIV. AZT now goes by the name zidovudine, but back then it stood for azidothymidine. AZT has been called by some as “the drug that had to work” (Garfield, 1993). It was fast-tracked through the drug approval process after a phase II trial showed that fewer people were dying on AZT than off it, so the trial was stopped and the drug was made available to the public. While it wasn’t a cure, AZT at least offered people hope…the hope of surviving long enough until better treatments were discovered.
The explosion of available medications over the ensuing years stands as a testament to human ingenuity. As more information was discovered about the virus and exactly how it interacted with cells and replicated, different medications were developed that could stop the virus at nearly every step along the way. Currently, there are dozens of HIV medications that broadly fall into seven categories based on how they work. The typical treatment regimen for an HIV-positive individual is called antiretroviral therapy (ART) and involves taking two or three of these medications lifelong. While it still hasn’t equaled a cure, effective treatment can now help HIV-positive individuals lead nearly normal lives with nearly normal life expectancies.
Treatment can also help people achieve an undetectable viral load count. What this means is that levels of HIV in the blood are so low, laboratory tests can’t detect it. This is different from a cure because it still requires being adherent to medications. If somebody with an undetectable viral load were to stop taking HIV medication, the virus would multiply and would be detectable by testing again.
One of the incredible things about having an undetectable level is that evidence shows it becomes impossible to transmit the virus through sexual activity. The campaign U=U (Undetectable = Untransmittable) has been spreading this message, encouraging HIV individuals to stay adherent to medication and empowering them to live normal lives. The chances of spreading the virus from mother to child during pregnancy and breastfeeding are also significantly reduced—but are not zero— when levels are undetectable, and the same is suspected of transmission by sharing needles.
But the question still stands, when will there be a cure?
Well, for two individuals, the answer is “it already happened.” In 2008, it was reported that one patient in Berlin was cured of HIV, and in 2019, a similar announcement was made about a patient in London. These two people are currently the only ones in history to have been cured of the virus. For good measure, some people avoid using the term “cure” and instead state that HIV in these patients has gone into remission. This means that the virus is no longer detectable in the blood after remaining off of all HIV medication for an extended period of time. (There was another person, the “Mississippi baby,” who was also believed to have been cured after contracting HIV from her mother and receiving aggressive treatment; however, the virus eventually reemerged.)
The problem is, the road to achieving a cure (remission) in these patients was a difficult one and is unlikely to be replicated on a large scale. Both patients had initially been diagnosed with HIV and were receiving ART as treatment. They each then developed a form of blood cancer – leukemia in the Berlin patient and lymphoma in the London patient. The Berlin patient went through chemotherapy, radiation, and two rounds of stem cell transplantation to replace his bone marrow. The London patient went through chemotherapy and one similar transplantation. Afterward, both went off their HIV medication and have maintained undetectable levels ever since. The kicker? The stem cells that were transplanted into each of these patients had a mutation known as CCR5-delta 32, which makes the cells resistant to HIV. This spelled good news for these two patients, but stem cell transplantation can be a tricky business (and comes with a high mortality rate and the potential for many other complications). In an age when ART does a good job managing HIV infection in most people, it is unlikely CCR5-delta 32 stem cell transplantations are going to be the widely adopted HIV cure we’ve all been waiting for. (Of note, a Düsseldorf patient underwent a similar transplantation and might soon be the third person to be declared “cured” or “in remission.”)
So then, what’s coming next? Are HIV-positive individuals destined to take pills for the rest of their lives or are researchers on the path of discovery?
Part of the problem with finding a cure for HIV is how the virus works. As a retrovirus, HIV not only enters the cells it is infecting – it inserts a copy of its genetic code into the genetic code of its host. It, therefore, becomes very difficult to target HIV without damaging the entire cell.
One of the most recent studies published on the matter describes a technique of going after incorporated HIV genetic material directly (Dash, 2019). In the study, researchers combined a drug delivery method known as long-acting slow-effective release antiviral therapy (LASER ART) with a gene-editing technique called CRISPR-Cas9. The result was the successful removal of HIV DNA fragments from the cells of humanized mice (mice that are carrying human genes). While this technique likely still has years of development ahead of it, it indicates one of the ways researchers are currently trying to beat HIV.
According to Avert, a charitable organization based in the United Kingdom that envisions a world with no new HIV infections, additional possible future cures for HIV break down into four categories (Avert, 2019):
- Techniques that kill all infected cells as well as ridding the virus from any reservoirs where it may be hiding in the body.
- Techniques that change the genetics of the immune cells so the virus can’t infect them.
- Techniques that make the immune system better at fighting the virus.
- Techniques similar to what happened with the Berlin and London patients, replacing an infected individual’s immune system with a donor immune system.
Which one of these possibilities (or some additional possibility that researchers haven’t thought of yet) will ultimately win out is anybody’s guess. While a cure likely will not be available for several years, we do at least seem to be getting closer, and many are confident that that day will come. Until then, the good news is that the currently available medications have made it so that HIV can be considered a chronic condition and living with it is very manageable for most individuals.
- Avert. (2019, July 17). Is there a cure for HIV and AIDS? Retrieved from https://www.avert.org/about-hiv-aids/cure
- Dash, P. K., Kaminski, R., Bella, R., Su, H., Mathews, S., Ahooyi, T. M., et al. (2019). Sequential LASER ART and CRISPR Treatments Eliminate HIV-1 in a Subset of Infected Humanized Mice. Nature Communications, 10(1), 2753. doi: 10.1038/s41467-019-10366-y. Retrieved from https://www.nature.com/articles/s41467-019-10366-y
- Garfield, S. (1993, April 2). The rise and fall of AZT: It was the drug that had to work. It brought hope to people with HIV and Aids, and millions for the company that developed it. It had to work. There was nothing else. But for many who used AZT – it didn’t. Independent. Retrieved from https://www.independent.co.uk/arts-entertainment/the-rise-and-fall-of-azt-it-was-the-drug-that-had-to-work-it-brought-hope-to-people-with-hiv-and-2320491.html
Dr. Tzvi Doron is Board Certified in Family Medicine by the American Board of Family Medicine and is Ro's Chief Clinical Officer.