A third man on the PrEP drug regimen has contracted HIV. PrEP, or pre-exposure prophylaxis, requires taking the FDA-approved antiretroviral drug Truvada, which has been proven to prevent HIV in non-infected people who take the drug everyday. From 2012 until 2016, there have been no known HIV transmissions by people who stuck to the PrEP program, but experts are still hesitant to label it 100 percent effective.

Those concerns turned out to be valid, when in February 2016, a Canadian man on PrEP contracted HIV. Later that year, another man came discovered that he had also contracted the virus. PrEP failed yet again when POZ, which focuses on HIV news, reported that a Dutch man taking Truvada tested positive for HIV last Thursday.

There’s no reason to panic yet: That’s only three cases in five years. In the cases reported in 2016, both men contracted rare, drug-resistant strains of HIV that Truvada does not protect against because it only contains two anti-HIV drugs, emtricitabine and tenofovir.

This newest case has experts more puzzled, though. Some experts speculate that the man’s sexual activity is the key to the drug’s inability to prevent infection.

At the Conference on Retroviruses and Opportunistic Infections, Dr. Elske Hoornenborg, an infectious disease specialist at the Public Health Service Amsterdam, reported that this new patient kept a diary detailing his sexual activity over the course of eight months. Over that time period, he had an exceptionally high number of partners and engaged in sex without a condom much of the time. He also reported that he was a heavy drug user at the time of his infection.

Dr. Hoornenborg thinks that his sexual history is relevant in this case because he was exposed to the virus. Because Truvada only contains those two anti-HIV drugs, it might not have been sufficient in combating such relentless levels of HIV in his body.

But as Dr. Hoornenborg told the audience at the conference, tens of thousands of people are on the PrEP regimen, and this seems to be the first case of it’s kind. She acknowledged that along with taking PrEP patients must also be coached in reducing risk-taking behaviors that might reduce Truvada’s effectiveness.

Three weeks after doctors were able to confirm that the man in question was indeed HIV-positive, they began to treat the infection, and his HIV is now undetectable.

In spite of Dr. Hoornenborg speculations, experts are still puzzled as to how this man became infected. Dr. Robert Grant, who was the head researcher on the study that initially proved PrEP’s effectiveness back in 2010, told POZ, “The good news is that the person is now doing very well on therapy,“ Grant said, "and his infection was caught early because he was in a PrEP program.”