First U.S. Failure of Truvada as PrEP Is Reported at IDWeek
A poster presentation at IDWeek, a yearly conference held by the Infectious Diseases Society of America, revealed that a 21-year-old Latinx man has acquired HIV despite consistently high adherence to pre-exposure prophylaxis (PrEP). This new report is unique for several reasons, primarily because this is the first known HIV seroconversion with verified adherence to PrEP in the U.S.
According to the report, the man initiated PrEP through a city health clinic in San Francisco. He was confirmed as HIV negative at the time he started the drug through rapid antibody testing and HIV RNA testing. He returned for follow up visits and was confirmed HIV negative at months three, six, and 10, again by antibody and RNA. Upon return at month 13 in early 2018, he tested HIV negative on a rapid test but positive with 559 copies/mL on an RNA test. A secondary test soon confirmed he was HIV positive with 1544 copies/mL. He was immediately initiated on emtricitabine/tenofovir alafenamide (Descovy), dolutegravir (Tivicay), darunavir (Prezista), and ritonavir (Norvir), and according to Robert Grant, M.D., M.P.H., of the University of California San Francisco, he has consistently maintained a suppressed viral load ever since.
The researchers were able to do identify that the man had a strain of HIV containing reverse transcriptase mutations L74V, L100I, M184V, and K103N. This suggests that he acquired a strain of HIV from a partner who used certain HIV drugs in the past but was not currently taking them. The patient's primary male partner was reported as living with HIV, not connected to medical care, and living with a strain of HIV resistant to the same mutations as the patient's strain. Upon learning of this occurrence, the partner was re-linked to care and found to have a viral load of 15,000 copies/mL at his first visit. It is not clear whether the partner would have returned to treatment if the patient had not tested positive.
Next, researchers sought to understand how this transmission occurred. Did it take place because a resistant strain of HIV broke through PrEP's protection? Or did issues of non-adherence make the patient more susceptible to acquiring this strain?
To learn this answer, researchers evaluated adherence by plasma, dried blood spotting, and hair sampling. According to Grant, "[The patient's] long hair allowed us to test by centimeters, which allowed us to go back and read drug levels from six months ago." From these measurements, researchers could see that the patient had used PrEP with strong consistency over the six-month period prior to his initial HIV-positive result. In other words, there is no doubt he had the maximal protection PrEP offers at the time of seroconversion, confirming that the resistant strain broke though.
As mentioned above, this case is unique as it is the first time a breakthrough case has been documented in the U.S. Since the U.S. Food and Drug Administration's approval of PrEP in 2012, over 180,000 people in the U.S. have used the drug without incidence. In two previous cases of seroconversion while on PrEP, it had been determined that the patients had strong adherence in the 90 days prior to testing HIV positive, but not that they were using the drug at the time of seroconversion, nor that they were confirmed HIV negative when they initiated PrEP. In no previously verified instance has a person in the U.S. acquired HIV under these circumstances.
So, what does this mean for PrEP's efficacy and viability in ending HIV transmissions? Very little, as Grant noted. "We know PrEP is greater than 99% effective," he said. "There are some cases where HIV will break through. We only have a handful of cases now, and next year, we'll probably have a handful more. Fortunately, these cases are caught early, treated, and suppressed quickly. The person goes from taking one pill a day to one pill a day. The biggest difference is stigma."
As a PrEP user myself, I admit that reading about this lends me pause. Is daily use really protecting me from HIV? Do I have a rational reason to be afraid? Will I be the next nameless patient presented on a poster board at a scientific convention on diseases? Then, I remind myself that if these transmissions were commonplace, we would have seen a lot more of them. If these resistant strains so easily "broke through" PrEP's 99% protection, we would have seen clusters of cases reported in 2015 in Toronto, where this initially occurred, and we'd be seeing a lot more of these events in San Francisco after this latest report.
However, instead of hearing about masses of HIV transmissions, PrEP seroconversions with verified adherence remains limited to three individuals in the world: one each in Toronto, San Francisco, and Amsterdam (the latter of which did not happen as a result of a resistant strain). With more than 356,700 people currently using PrEP worldwide, three cases still places HIV's protection at much greater than 99%. Or as Grant said: "We talk about these rare cases when they happen. It's not as sexy to talk about all the cases where that didn't happen, and how well PrEP protected people under the same exact circumstances."
While writing this article, I received an alert that the U.S. Centers for Disease Control had reported that 80,000 deaths in the U.S. were attributed to the flu during the 2017-2018 season. I use this as a reminder that HIV transmissions on PrEP are scary, yet infinitesimal compared with other dangers in the world. Instead of fearing and stigmatizing sexual connections, perhaps we can learn from these reports how to mitigate risk, practice reasonable caution, and increase empathy for others. Or, as Grant reflected: "Maybe we can use these cases to talk about reducing stigma and loving people living with HIV. It is really sweet when people enjoy sex, whether or not there is HIV present. That is humanity's real victory over HIV."