Last month, the global public health effort to eradicate AIDS confronted a setback. Since 2012, people who want to protect themselves against HIV-1 infection have been able to take a daily pill, a so-called pre-exposure prophylaxis drug that kills the virus before it can take hold. But that pill may not be as powerful as we’ve hoped. In February, researchers reported that a 43-year-old Canadian man contracted HIV despite taking the drug for two years—the first documented case of its failure.
The news is eye-opening. Prior to this case, pre-exposure prophylaxis had shown to be tremendously effective. One study touted a reduced risk of infection of 92 percent. Another more recent study reported that 100 percent of its nearly 10,000 participants remained HIV-free. With those reassurances, health agencies like the CDC endorsed prophylactic drugs as an essential way to reduce the risk of contracting HIV-1. With perfect use, the drug could be up to 99 percent effective.
So was this man’s case just one of bad luck? In part, yes. He took his medication just as directed. But he was exposed to a strain of the virus that had grown resistant to Truvada, the FDA-approved drug used in pre-exposure prophylaxis. He is an outlier—the unfortunate 1 in 100. But his case also illustrates a fundamental flaw: Drugs—no matter how effective they are—may never be enough to fully eradicate HIV-1. Only a vaccine will.
Drugs—no matter how effective they are—may never be enough to fully eradicate HIV-1. Only a vaccine will.
Anti-retroviral drugs like those used in pre-exposure prophylaxis are the best tools we have to treat and prevent HIV-1 infection. But they’re not foolproof. For HIV-negative people on Truvada to prevent a new infection, the drugs must be taken like clockwork to keep the virus at bay. Adherence to the rigorous drug regimen has been described as the “Achilles’s heel of pre-exposure prophylaxis.” A person is at greater risk of infection if they miss even one in twenty doses.
Equally important for protection: People already infected with the virus must strictly adhere to their own anti-retroviral regimen. Much like missing a dose of antibiotics can create antibiotic-resistant bacteria, missing a dose of anti-retrovirals can help create strains of HIV-1 that can evade preventive treatment and fail to protect uninfected people in the future.
It’s important to remember—HIV-1 is so devastating because it attacks the very immune cells meant to keep us healthy. The virus also demonstrates the highest reported mutation rate of any biological entity, allowing it to quickly develop new defenses against drugs and host immune systems. This one-two punch means the virus is extraordinarily difficult to wipe out once infection is established.
Mutation is how viruses survive in the face of drug compounds designed to knock them out. If a patient stops taking their medication, they inadvertently create viruses that can grow at the reduced drug dosage. They may start taking their meds again, but the virus has already become resistant to that dose of drugs. So the patient needs a higher dose of drugs. Then they miss a dose again, creating increasingly drug-resistant viruses.
One study estimated that 76 percent of Americans living with HIV-1 were resistant to one or more anti-retroviral drugs.
Alarmingly, one study estimated that 76 percent of Americans living with HIV-1 were resistant to one or more anti-retroviral drugs. The end result is increased transmission of drug resistant HIV-1, and decreased effectiveness of prophylactic drugs.
So, Truvada is the best tool we have right now to prevent HIV-1 infection, and that tool has shortcomings. Public health agencies need a better long-term solution for prevention: a vaccine.
Vaccines prevent infections and reduce the need to use drugs altogether. Instead of taking years or decades of pills, a vaccine teaches the immune system to combat viruses on its own—with a single injection (or very short course of shots). Vaccines are relatively inexpensive, and have an unimpeachable record of safety and effectiveness.
These factors are precisely why scientists have poured more than 30 years of work into the search for an HIV-1 vaccine. But while researchers are optimistic that an effective vaccine is on the not-too-distant horizon, they’re still not there yet.
2009 saw the first report of a successful clinical trial for an HIV-1 vaccine in Thailand, reducing infections by over 30 percent in vaccinated subjects. It provided the first proof that a vaccine could stop HIV-1 in its tracks. Since then, research has accelerated. New scientific insights are being published nearly every day.
One such discovery is an understanding of antibodies created by our immune systems that—if present before a person is exposed to the virus—are capable of completely protecting against HIV-1 infection. These findings have allowed researchers to work toward designer vaccines that can allow uninfected people to remake these antibodies through vaccination.
An effective vaccine to prevent HIV is still a dream, but I firmly believe we have never been better positioned to make it a reality. The key is to build on the momentum we’re seeing, bring the latest technology and innovations to support the effort, and double down on investments in HIV-1 vaccine development. Vaccine research currently makes up less than 10 percent of the total yearly investment in HIV-1/AIDS in the United States. We can, and should, do better.
This can’t be an either-or discussion. Pre-exposure prophylaxis will save many lives and we should strongly support any solution that will do so. But its implementation should not come at the expense of efforts to develop a vaccine—the best chance we have to wipe out this virus for good.