COMMENTARY

A Precaution About PrEP in HIV Prevention

Paul E. Sax, MD

Disclosures

November 12, 2018

Hi. This is Dr Paul Sax from Brigham and Women's Hospital and Harvard Medical School.

Today I'd like to review a couple of new findings about pre-exposure prophylaxis (PrEP) for HIV. The first is a study[1] that has been presented before, but now it's been published, demonstrating that with the introduction of widespread PrEP in New South Wales, Australia, there was a marked reduction in the number of new HIV diagnoses. Specifically, there were 3700 participants in an 8-month period who started PrEP in 2016. They had excellent adherence and only two individuals became infected during this time. These were high-risk men who have sex with men. In the entire region there were 295 new diagnoses before the intervention and 221 after the intervention, which is a 25% relative risk reduction. My colleagues in Australia say that they very rarely see new diagnoses these days, and it really does show that on a population basis, the introduction of PrEP to a high proportion of the individuals at risk really can reduce incidence. That is finding number one.

The second thing I wanted to mention is a cautionary note. It was another case of PrEP failure that was presented at ID Week.[2] Remember, this intervention is not 100% effective. The failure case was a 21-year-old man who had been started on PrEP the year before he presented. When he presented he had a newly detectable HIV viral load at a very low level. This was confirmed when he came back and started antiretroviral therapy. His baseline genotype, importantly, had resistance mutations as follows: the M184V mutation, the L74V mutation, and the K103-end mutation. The M184V mutation confers resistance to emtricitabine, which is part of PrEP. The virus was checked phenotypically and found to be susceptible to tenofovir, which is the other part of PrEP, but remember that the L74V mutation can have some impact on tenofovir's susceptibility also. This is another case of PrEP in an individual who acquired a virus that was resistant to at least half the components of TDF/FTC, which is what is used for PrEP right now.

Notably, all of the other PrEP failure cases except for one have been individuals who acquired a drug-resistant virus. In this case, they confirmed that the individual was taking his PrEP by using hair samples to test for drug levels. They were able to find and test the source individual's virus and found that it had the same resistance mutations.

On the good-news side, if you expand PrEP in a population at risk, you can markedly reduce the incidence of HIV infection. On the other hand, this is not 100% effective and we should still counsel our patients that there is a small risk that they could still acquire HIV if they have unprotected sex.

That's a summary on two recent findings about PrEP. Thank you for listening, and I'll see you next month.

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