A Melbourne man participating in a trial of PrEP sparked fear about possible resistance to the antiretroviral medication after testing positive for HIV last week.

Hundreds of thousands of people currently use Pre-Exposure Prophylaxis (PrEP) daily to protect themselves from contracting the virus, as it has proven to reduce HIV transmission by up to 99%.

There have only been two confirmed cases of men becoming infected with a drug-resistant strain of the virus while properly taking the medication, one in Toronto and one in New York, with another report out of Amsterdam that is still being investigated.

The fourth report now comes from the infected Australian man, which was documented at a Melbourne clinic during a PrEP study that has a wait list of over 600 people.

University of Melbourne professor Sharon Lewin told The Age that doctors will now analyze the man's usage of the drug, in addition to studying the virus itself for resistance, but that it doesn't negate the proven effectiveness of the medication overall.

"I don't think there is any reason for alarm here," Lewin said. "PrEP works and any rare cases of failure need to be investigated fully so we fully understand why this can very rarely happen."