A friend of mine recently had an unprotected sexual encounter. He went to a party, got drunk, and one thing led to another with a guy he'd never met before. He was concerned about HIV, but I remember his justification: "the guy was on PrEP, so I don't think there's much to worry about."
I realized that, while I knew a lot about how PrEP worked (I'll get to that!), I knew nothing about how effective it was as a prophylactic agianst HIV. Last week's excitement over a newly published Kaiser Permanente study got me to finally drill into the subject.
News coverage has ranged from dramatic over-interpretation:
In New Study, HIV Prevention Pill Truvada Is 100% Effective http://t.co/CTWlQquKdt— Slashdot (@slashdot) September 4, 2015
Truvada protected 100% of participants in new study from HIV http://t.co/T2H5wyfvJt— huffpostgay (@huffpostgay) September 5, 2015
To cautiously optimistic:
An insurer says its clients on a daily pill have stayed HIV-free http://t.co/G0l7ZpPpkG— The New York Times (@nytimes) September 7, 2015
Kaiser is well known for doing great longitudinal studies with large cohorts, so I was anxious to get my hands on the paper and read it. Being a child of the HIV/AIDS era, I was hoping for a biotechnological breakthrough!
What is PrEP?
Pre-exposure prophylaxis (PrEP) is a relatively new means of preventing HIV transmission. It involves taking a daily dose of a reverse-transcriptase inhibitor called Truvada that is typically used in the treatment of HIV-infected patients.
Retroviruses like HIV package up their genome in the form of RNA. Once their RNA is injected into a cell, they use an enzyme called reverse-transcriptase to convert their genetic code to DNA and integrate into the host cell's genome. Drugs can inhibit either the injection or the reverse-transcription process in order to slow the progression of HIV through the body. Truvada does the latter.
In an uninfected person, Truvada works in much the same way. If you become exposed to HIV, the virus is inhibited from reverse-transcribing and integrating into your genome. Pretty cool! The only catch is that you have to keep an effective dose of the drug in your bloodstream at all times. It's not enough to just pop a pill before you're ready to party.
It's true: none of the individuals on PrEP in the Kaiser study contracted HIV during the study. Great news, but in order to know how effective PrEP was, we need to compare to an equivalent control group of individuals taking a placebo. This study had no controls.
There's a very practical reason why there were no controls: this was data collected from high-risk individuals who were actively seeking PrEP. It would have been unethical to give some of them a placebo, knowing that it would put them at increased risk of infection.
The authors were upfront about this shortcoming and attempted to use a control group from the unrelated PROUD study, but there are obvious differences in the cohorts that make the comparison flawed, at best. Again, on an ethical basis I can't fault them, but it is a gigantic asterisk on any conclusion we draw from the data.
Bigger, Better, Older Studies
The other main shortcoming is the study size. The number of people in the study, the average length of PrEP use, and the total number of person-years are all a fraction of previous studies. The 2010 iPrEx trial had about ten times as many person-years of PrEP use and a proper control group to compare against (this was before PrEP was demonstrably useful as a prophylactic measure).
That data shows that PrEP has an effect, but an imperfect one. The PrEP cohort had only 36 HIV infections compared to the 64 in the placebo group. This means that Truvada provides somewhere between 15% and 63% reduction in HIV infection. Impressive, but nowhere near 100%.
The iPrEx trial has its own flaws, of course. Their cohort was international, with the largest group coming from South America. There may be cultural and economic factors that make the data less comparable to "first world" nations. The smaller PROUD study in the United Kingdom, for example, has higher estimates of efficacy, putting it at 86%.
While the Kaiser study doesn't add much to our knowledge of PrEP effectiveness, it did have some interesting behavioral findings among people that initiated PrEP:
- PrEP users were more likely to have multiple sexual partners than people who declined PrEP
- While there were no HIV infections diagnosed, 30% of PrEP users contracted some other form of STI
- 41% of surveyed PrEP users said they decreased condom use
Despite being relatively uncommon in the United States, HIV is terrifying and definitely scares me out of certain sexual exploits. Irrationally, I don't worry as much about chlamydia or gonorrhea (I absolutely should worry about these). I'd probably be more open to unprotected sex if I honestly believed I was immune to HIV.
The data suggests to me that lots of people feel immune once they start on PrEP. Headlines that outright state 100% effectiveness only re-enforce that misconception. Truvada simply doesn't meet the bar for a front-line defense against HIV infection and the CDC still recommends condom use.
I guess that's a bit disappointing. Though, to be perfectly honest, I'd rather carry a rubber in my wallet than pop an anti-retroviral pill every day for the rest of my life, anyway.