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CHICAGO -- Pre-exposure prophylaxis (PrEP) against HIV is highly effective when it's used properly.

But it's not perfect, as illustrated by a rare case of infection with a multidrug-resistant HIV strain, according to , of the Cleveland Clinic.

The infection occurred while the patient, a gay man, was on daily PrEP with tenofovir/emtricitabine (Truvada) and in a relationship with an HIV-positive man whose virus was suppressed by therapy, Grossman told reporters at the conference here.

Analysis of the patient's proviral HIV DNA showed mutations in the reverse transcriptase gene -- K65R, M184V, K103S, E138Q, and Y188L -- that are associated with resistance to nucleos(t)ide reverse transcriptase inhibitors (including tenofovir and emtricitabine) as well as to non-nucleoside reverse transcriptase inhibitors, Grossman said.

The analysis also showed that the HIV strain carried by the man's partner was not the same as that found in the patient, suggesting a separate source, Grossman said.

Indeed, both men had twice been sexually involved as a couple with separate third parties in the weeks after the patient started PrEP and before his HIV was detected in a routine screening, Grossman said. In both episodes they had unprotected sex, he added.

Unfortunately, the outside partners could not be traced, Grossman told MedPage Today, making it impossible to pin down the source of the infection.

The case is the second with Truvada, but Grossman said the reports have to be put in the context of more than 100,000 people in North America taking PrEP.

"Those are pretty good odds," he told MedPage Today.

PrEP with Truvada is a single pill meant to be taken daily in the context of safe sex but in some situations -- with a partner whose virus is known to be suppressed, for instance -- not using condoms can be a "perfectly rational choice," Grossman said.

"With an unknown partner," he said, "the risk is that you will meet someone with resistant virus."

Aside from a reminder to people on PrEP that complete protection is not guaranteed, the case also holds a lesson for health care providers, Grossman said -- that routine testing can sometimes be misleading.

The patient had tested negative for HIV for several years, as late as December 2015. He started PrEP Jan. 1, 2016 and was adherent by self-report, which was confirmed by later testing of dried blood spot and hair.

But in early May, a routine 4th generation test for HIV was reactive, as was a nucleic acid amplification test, although a Multispot HIV 1/2 was non-reactive. Repeat testing 2 weeks later yielded identical results, but the man had no detectable viral load or impact on his immune system.

The integrase inhibitor dolutegravir (Tivicay) was added to the Truvada near the end of May.

A third round of testing in early June still found no viral load and a reactive 4th generation test, but this time both the nucleic acid amplification and Multispot tests were negative. That round -- taken in isolation -- would have prompted many doctors to rule out HIV, Grossman said.

It's highly unusual that a patient would be in the acute stage of infection without a high viral load, Grossman said. "I've never seen that before," he said.

The rare cases of breakthrough infection "should never be a reason for not offering" PrEP, commented, of the San Francisco health department.

"PrEP is still highly effective," she told MedPage Today, "but it's not 100%."

The apparently paradoxical finding of acute infection without a high viral load might possibly be explained by a lower fitness of the multidrug-resistant strain, Buchbinder said. "It might be that the virus is so impaired (by the mutations that led to resistance) that it was able to establish an infection but you're still driving it down" by taking PrEP, she said.

"What we don't know is what would have happened if (the patient) had come off PrEP," she said.

The man is currently on a regimen of Truvada, dolutegravir, and cobicistat-boosted darunavir (Prezcobix) and has maintained viral suppression, Grossman said.

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