Worried About That PrEP-Resistant Strain of HIV? The Doctor Who Discovered It Has Some Advice.

Truvada, the drug combo currently used as PrEP.

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Last week, David C. Knox, a physician and researcher based in Toronto, caused a small earthquake in the world of queer sexual health. Knox offered a presentation at the Conference on Retroviruses and Opportunistic Infections in Boston in which he revealed the first known case of a patient contracting HIV despite confirmed adherence to PrEP—the HIV prevention strategy that currently comprises taking a daily pill (Truvada) that blocks the virus from taking hold after an exposure. Although PrEP has been proven to prevent the transmission of HIV with 99 percent efficacy, this particular case has been discussed as the unfortunate one percent: The highly uncommon strain of HIV the patient encountered showed various levels of resistance to many drugs, including those in Truvada.

But is the one percent figure—and the relative confidence it still affords—totally accurate? What variables are in play? And if the percentages are not as simple as they seem, how would that information help PrEP users take further control of their sexual health? I spoke with Knox to find out.

“The thing that’s so amazing about PrEP is that these are people who are taking charge of their sex lives and sexual health and are getting STI and HIV testing every three months,” Knox began, referring to the quarterly surveillance testing required as part of the PrEP regimen. (The frequent testing is a good thing in itself, considering reports from physicians who are seeing increases in STIs like gonorrhea, chlamydia, and especially syphilis among men who have sex with men.) But increased personal responsibility aside, does the unsettling case that Knox observed mean that PrEP is less effective than we thought?

Not really. According to Knox, there are four things that must occur in order for seroconversion to take place if someone is properly adhering to PrEP. The individual must have sex with an HIV-positive partner who has a PrEP-resistant strain of the virus; his partner must have a “high viral load,” usually indicating that he is not on treatment or that treatment is failing; the two must then engage in condomless, or “bareback,” sex; and finally, the individual must contract the virus from the sexual act itself, an occurrence that is itself weighted by a range of variables, including sexual position (topping is generally less risky than bottoming), the presence of injury, and increased susceptibility due to other STIs. For all of these factors to align at once in a given encounter—especially and most importantly the presence of drug resistance—is highly unlikely; and of course, some of them, like condoms or specific acts, are ostensibly under the participants’ control. Even so, now that a PrEP-thwarting strain of HIV has been identified, the specific question of barebacking is worth reevaluating. All things being equal, if somebody who adheres to PrEP comes into contact with a resistant strain while engaging in bareback sex, would the risk of contracting the virus be the same as it is for somebody who’s engaging in bareback sex but not on PrEP?

“There’s zero data on that,” explained Knox. “We don’t know. It’s a very tricky question. There’s no answer for it, yet. There might never be, in fact.”

This data would be a significant factor in one’s decision to have, or to continue to have, bareback sex while on PrEP. Given that there’s only been one reported case in the literature with its particular profile, the PrEP-resistant strain is thought to be incredibly rare. But cities can be their own ecosystems when it comes to STIs; could a strain like this begin circulating among particular communities, even among PrEP users who thought they were protected? “Absolutely that’s a possibility,” said Darrell Tan, who was the senior author on Knox’s paper and who leads the PrEP-atory5 study out of St. Michael’s Hospital in Toronto. It is important to note that this doesn’t mean that this strain is spreading now, just that such a situation is possible.

The truth is, despite PrEP’s powerful efficacy stats, there’s still a lot to learn. “The thing that we don’t know yet is how frequent this type of resistance pattern is in the community,” Knox said of the “breakthrough” strain. “That’s data that we need to be looking for and start monitoring. How frequent are these mutations that we see in HIV? So, that’s really the outstanding piece that we need to start looking at.” Gathering this data will require a concerted public health effort.

“Best case scenario is that if someone does become HIV positive, whether or not it’s from a resistant strain or non-adherence or whatever, while on PrEP, you catch that virus very, very quickly, and we put the patient on medications to make their viral load suppressed very quickly,” said Knox. “That’s a really, really good thing, not just for the patient themselves but also to prevent transmission of the virus to other people.”

“Worst case scenario, if this is something that is circulating in Toronto right now, this strain of HIV, then we might see it again in the future in other patients who are taking PrEP,” he added. “[B]ut you have to underscore, this is exceedingly rare, so rare that it’s the first documented case ever.” 

Even as he advised against immediate alarm, Knox did sound a note of caution. “Up until this case was released on Thursday, if you looked at everything that people talked about online,” Knox said, “the studies that they quoted they were saying if you take this medication every single day, you don’t have to worry because there have been no reported breakthrough infections of HIV…until Thursday. But we’ve been speculating for a very long time that this could potentially occur because we are preventing HIV the same way we treat HIV with the exact same medication, so there’s an inherent problem there.”

While the science is evolving, the takeaway is that this case simply helps us better understand the full risks involved in the sexual choices we make. It’s a way for those who are already taking control of their sexual lives and health with PrEP to take even more control. The unknowns regarding relative contraction risk and the prevalence of the PrEP-resistant strain should not discourage men who are taking PrEP or those who are considering taking it. In combination with condoms, it is by far the most effective tool in the prevention of HIV and, according to the CDC, has the potential to prevent an estimated 48,000 new HIV infections in the United States by 2020, even if current testing and treatment rates don’t improve.* We’re still exploring new drugs and technologies for PrEP, and there are sure to be more lessons along the way.

As for those already on the regimen, Knox had one piece of advice: “Keep using PrEP, and use condoms wherever possible.”

*Correction, Mar. 4, 2016: This post originally misstated the number of new HIV infections PrEP could prevent in the U.S. by 2020 without other changes in treatment and testing, according to the CDC.