A few people that I talked to yesterday, in the wake of the news of the first documented case of a supposed daily PrEP user who nonetheless contracted a strain of HIV with drug resistance, worried about an almost gleeful, “See, told ya so!” sentiment they were seeing in some gay men’s responses. At this point in my life, I am actively trying to avoid the unreasoned opinions of strangers, particularly when these opinions come with the smell of disregard for the community to which those who voice them belong (if not outright self-hatred). That’s to say that I didn’t really interact with any of that. But it is plausible that because PrEP is a discursive lightning rod, its detractors feel justified and some sense of happiness or pride over what many have taken to be solid evidence that PrEP is not 100 percent effective in eliminating HIV—something, by the way, that no expert I’ve ever read has ever attempted to argue. In fact, every doctor or researcher or activist or counselor that I’ve ever talked to has been extremely careful not to claim 100 percent PrEP efficacy.
The people who feel good about this news were only going to feel good about this news. That’s a shame. Moving on, to those who were agnostic about PrEP, as well as the true believers whose faith has been shaken, I would like to present just a few thoughts from some very smart people who know a lot about this stuff. This is just some perspective that I think is worth considering.
BETA Blog, reporting from the Conference on Retroviruses and Opportunistic Infections in Boston, where the case of HIV contraction in a daily PrEP user was reported, spoke with Robert Grant, MD, MPH. Grant reported the finding at CROI, and he also is the principal researcher on iPrEx, a multiyear clinical trial of PrEP use in men who have sex with men. It is from iPrEX where the 99 percent efficacy figure derives.
The prevalence of viruses that are highly resistant to both tenofovir and FTC are rare, and are even less likely to be transmitted. Among 9,222 people taking PREP in trials, this kind of virus was never once seen.
The prevalence of this kind of virus among recently infected persons is less than 1%. Maybe much less. If PrEP is not fully effective against viruses that are HIGHLY resistant to both drugs in FTC/TDF PrEP, the efficacy of PrEP when taken may decrease from 99% to 98%. Or from 99.9% to 98.9%. Or from 100% to 99%. The decimal points are not certain.
My point is that one chooses whether to focus on the glass 99% full or 1% empty.
After 32 years experience with HIV research, I have learned to never say “never.”
That’s to say, you can focus on this so far isolated incident, or you can focus on the great number of studies that prove PrEP’s effectiveness, again and again and again. For example, last year Kaiser Permanente Medical Center in San Francisco released the results of a 32-month study of over 600 daily Truvada users that found not one instance of a new infection within that group.
“There are more than 40,000 people using PrEP in the U.S. and this is one case,” offers James Krellenstein, a consultant to Treatment Action Group and a member of ACT UP New York. “That’s a pretty extraordinary success rate that is far superior to the efficacy of condoms in preventing HIV or birth control in preventing pregnancy. It’s kind of odd that we’re making such a huge deal about this one case, considering that PrEP is still the most (or second most) effective tool in preventing HIV infection that has ever been developed. No one says when a condom fails to prevent HIV acquisition, don’t use condoms. And the fact remains that people who are using condoms and not using PrEP are at much higher risk of acquiring HIV than people who are not using condoms and using PrEP.”
For a breakdown of numbers, I checked in with David Glidden, professor of biostatistics at UC San Francisco who has also served as the statistician in the iPrEx study and was instrumental in my own understanding of PrEP’s efficacy numbers. He sent me the following by email:
My “quantitative take”
- This is one case — out of > 40,000 people who have taken PrEP and research experience stretching back a decade.
- The infecting virus was very exotic and 0.44 percent of viruses infecting people are even close to similar (Chan et al, 2012). This has rarer features.
- At the same meeting where the case was presented, Kaiser Permanante presented their PrEP experience. It has seen no infections during PrEP care; however, 2 people had their coverage lapse and left the program. When they returned to the program, they were HIV+.
- I am 2 times as concerned about Kaiser data as I am about the Toronto case.
My informal “take”:
- PrEP remains the most powerful and rigorous tested HIV prevention tool ever developed. We should, by orders of magnitude, be more concerned about barriers to, ignorance of, and nihilism about PrEP. ~50,000 people are HIV infected each year — we have our work cut out for us.
I also spoke with Dr. Demetre Daskalakis who’s the assistant commissioner at the New York City Department of Health and Mental Hygiene’s Bureau of HIV Prevention and Control, and a gay health warrior. Daskalakis estimates that he has 50 patients on PrEP. He was present at CROI when Grant presented his finding. Here’s his takeaway:
Whenever there’s a biological intervention, there’s always a way to overcome it. That’s why I’m very cautious about never saying that PrEP is 100 percent anything. There’s always a possibility of figuring out a way of how to overcome it. The majority of viruses that are transmitted tend not to be resistant to the drugs in PrEP. Is it possible that someone met a virus that had enough baseline resistance to the drugs in PrEP to potentially allow for transmission? It’s possible, which is why I think rather than being like, ‘Oh my god, PrEP is over,’ the better message is, ‘Use condoms whenever possible.’ That reduces your risk of exposure. I know that’s not 100 percent, either, but a lot of the guys I have on PrEP use condoms at least some of the time. I have guys on PrEP, for instance, who use condoms with certain kinds of hook-ups and not others. Is it based on lots of data? No. But statically speaking, from my perspective, every time you use a condom, you reduce your risk no matter what, so groovy.
The other lesson this tells us is: Test for HIV every three months like you’re supposed to. We see people coming in on PrEP, and they need to get tested every three months, and it’s not really an, if, or could, or, ‘Maybe I’ll try.’ It’s that every three months of HIV testing makes sure that if they do get HIV, they can do what they did for this guy [in the study, whose HIV reportedly now is at undetectable levels in his blood] and put him on meds right away. That guy’s the dreamscape. If you get HIV on PrEP and you’re detected early on, you want to be on meds and you want to end it. You want to be undetactable and good to go. Rather than being a giant piece of bad news, this is more a reinforcement of what we already know.
Seems like this level of clarity from experts should be particularly useful during a time like this.