Overview

If you take PrEP daily as directed, it is close to impossible to contract HIV. In almost every case where someone tested HIV-positive after starting PrEP, the reason was either (a) they did not take the medication as directed or did not take it at all, or (b) they were already HIV-positive when they started PrEP.

However, no medical intervention is 100% effective, including PrEP. There are three documented cases, out of about 300,000 PrEP users, where someone contracted HIV despite adhering to PrEP. Their doctors are confident that these three people took adequate doses of Truvada (at least four times per week) – in two of the three cases this was confirmed through blood tests. But they still tested HIV-positive. These are rare exceptions to the overwhelming effectiveness of PrEP.

How did this happen? Two of these men contracted extremely rare strains of HIV that had resistance to both of the drugs in Truvada. [Note 1] The third contracted a non-resistant strain of HIV, in a case that involves many unusual factors and is still under investigation. [Note 2]

It’s important to note that even an infection with a resistant strain of HIV is treatable. All three of the patients mentioned above responded well to treatment, and their viral loads were undetectable within weeks – meaning they cannot transmit HIV sexually to anyone else. Like most people living with HIV, these men can expect to live normal, healthy lives.

Truvada-resistant HIV

The medication we call Truvada contains two different drugs: tenofovir (TDF) and emtricitabine (FTC). A strain of HIV that is resistant to both these drugs could potentially break through the protection of PrEP. This is a very unusual circumstance: in studies of two cities, only about 0.001% of new HIV cases involved strains that were resistant to both TDF and FTC [Notes 3, 4].

A resistant strain alone is not enough to put a PrEP user at risk. HIV, whether resistant or not, can only be transmitted sexually if the HIV-positive partner has a detectable viral load. Furthermore, the same mutations that make HIV resistant to medications can reduce their capacity to replicate, spread, and cause disease. Many factors have to coincide for an infection to take place. There are only two documented cases of an adherent PrEP user contracting a resistant strain of HIV.

There is no indication that Truvada-resistant strains of HIV are becoming more widespread, or that PrEP is becoming less effective. These cases are likely to remain very rare.

Infection with Non-resistant HIV

One patient in a PrEP study contracted HIV that was not resistant to the drugs in Truvada, despite adhering well to daily PrEP. This had never before been observed, and researchers are investigating the case, focusing on several unusual factors.

As part of the study, the man kept careful records of his sexual behavior. He reported an average of 56 anal sex partners per month, including about 30 episodes of condomless sex per month. On average he had condomless sex on 16 days per month, averaging 3.7 partners on each of those days. He reported recreational drug use, including mephedrone, GHB/GBL, ketamine, cocaine and amphetamine. He injected ketamine twice but said he used sterile needles, which suggests the HIV was contracted sexually, not by needlestick.

It’s worth noting that the man reported similar sexual activity before starting PrEP and did not take additional risks because of PrEP. Rather, he sought out PrEP through the research trial because he was concerned that his behavior put him at high risk for contracting HIV. Researchers are grateful to him for his cooperation in the study, which may help reveal important new information about how HIV infection occurs and how PrEP blocks it.

What Does this Mean for You?

Scientists have estimated that PrEP reduces the risk of HIV infection by about 99% when taken daily. These three cases, out of about 300,000 users worldwide, still place PrEP’s risk reduction figure at well over 99%. (Note that “99% efficacy” does NOT mean that 1% of PrEP users will get HIV. The actual figure is a tiny fraction of that). [Note 5] As more and more people start taking PrEP, we can expect to see a small number of exceptional cases like these – it is a simple matter of statistics. These cases are not surprising, they are likely to remain rare, and they cast no doubt on the effectiveness of PrEP.

Let’s keep some perspective. It’s human nature to focus on bad news while overlooking the good. The news media tend to reinforce this bias. There are hundreds of reports about plane crashes – but you’ll never read: “Nearly 1 billion passengers flew safely in the U.S. last year; only nine died.”

By any measure, PrEP is extraordinarily effective — more effective than many preventive treatments and vaccines (measles: 93-97%; mumps: 78-88%; flu: 51-79%). [Note 6] Many thousands of infections are *avoided* every year by PrEP users – these are people who would have become HIV-positive without PrEP, but didn’t. PrEP played an important role in a 40% reduction in HIV infections – over the course of a single year – among gay men using sexual health clinics in London. [Note 7] In the U.S., the CDC estimates that by 2020 PrEP, along with increased testing and treatment, could reduce the total number of new HIV infections by 70%. [Note 8] After years of stubbornly high infection rates (currently about 40,000 a year in the U.S.), that’s good news indeed.

Discussions of "PrEP Failure" in the PrEP Facts Group

PrEP Facts focuses on empowering members and providing them with accessible, up-to-date, scientifically vetted information. Rumors are often poorly sourced, provoke argument and discord and can be an opportunity for trolls to disrupt the group. As mentioned above, when a rumor spreads of “someone getting HIV while on PrEP,” there is a high likelihood that this is not a case of medication failure, but of human error. When such anecdotal reports are shared in the PrEP Facts group, they may meet with skeptical questions until they have been scientifically confirmed – a process that can take many months. This is not a judgment on an individual reporting that he or she got HIV while on PrEP. It’s just how science works.

If You Test HIV-positive while on PrEP

In the unlikely event that you believe your PrEP regimen has failed, it is important for your doctor to report your case promptly to your country’s drug regulatory agency (FDAin the United States ) and Gilead if you take brand-name Truvada, or the manufacturer of whichever generic version you may be taking. Leading scientists who were involved in developing PrEP are studying these rare cases in an effort to make PrEP more effective in the future. We urge you to contact them as well so they can learn more from your experience and offer their treatment advice. They need to be informed quickly in order to gather evidence before it fades. The PrEP Facts admins are ready to provide other resources and support during a difficult time. The (very few) PrEP users who have had this experience are also ready to offer their support (ask the admins to connect you). But remember: if you are adhering properly to PrEP, this is very, very unlikely to happen to you.