Pre-exposure prophylaxis for HIV: panacea or Pandora's box?

For the video version of this post, click here. Pre-exposure prophylaxis for HIV - PrEP - basically entails taking a medication, typically a combination pill of tenofovir and emtricitabine to reduce the risk of acquiring HIV. PrEP is highly efficacious, with several randomized trials demonstrating a sharp reduction in transmission rates when PrEP is used in high-risk populations. In fact, among men who have sex with men, you need to provide PrEP to about 12 people to prevent one HIV infection.  That’s a very low number needed to treat for such a costly disease.

But efficacy isn’t the same as effectiveness. Efficacy is an ideal. Clinical trials follow their patients extremely closely, ensure they are taking their medication, and select their participants very carefully.  Effectiveness is the real-world performance of a drug, and, until now, we haven’t had great data to see how PrEP would work in practice.

And there have been concerns. PrEP should be used with a condom, it doesn’t replace a condom. It can’t be taken immediately prior to risky sexual behavior - it’s a daily medication. There is a low, but real, risk of kidney dysfunction with the drug. But the real controversy surrounds a small but vocal group of physicians and AIDS activists who suggest that PrEP will ruin so-called “condom culture”, opening the door to less safe sex, increased sexually transmitted infections, and even an increase in HIV transmission rates.

That’s why this article, appearing in JAMA Internal Medicine is so important.  The study followed 557 men who have sex with men and transgender women in three clinics across the US for about a year. All were HIV negative, but at increased risk of HIV infection, and all were provided PrEP free-of-charge.

Adherence was high - over 80% of individuals had therapeutic tenofovir levels when checked. Encouragingly, adherence was highest among those who engaged in the highest risk sexual behaviors. That’s right - our patients at risk understand they are at risk.

Over the course of the study, there were 2 new HIV infections, both in men with subtherapeutic levels of the drug. Based on baseline rates we would have expected around 11.  But that impressive result is not what really matters in this study.

Rates of receptive anal sex without a condom didn’t change at all over the course of the study.  Sexually transmitted infection rates didn’t change. In other words, the availability of a drug that can really prevent HIV transmission didn’t open some time portal to 1983. PrEP did not destroy condom culture, not that condom culture is all that pervasive. This is one of those situations where we have to respect the intelligence of our patients.  Educate them clearly on how this medication is to be used, and trust that they, as consenting adults, will use the drug the right way.