Has Anyone Gotten HIV When They Were on PrEP?

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Pre-exposure prophylaxis (PrEP) was initially approved by the U.S. Food and Drug Administration (FDA) in July 2012 due to its exceptional ability to prevent new HIV acquisitions. One of the persisting fears people may have when starting PrEP is wondering whether a risk remains of contracting HIV while on PrEP without using an additional barrier method (i.e., condoms) that we've become accustomed to seeing as the gold standard definition of "safe sex."

The Research Behind PrEP

Truvada (tenofovir/FTC) as PrEP was approved on the data from two research studies -- iPrex and PARTNER -- that took place between 2007 and 2010. At the time of the FDA approval in 2012, zero new HIV cases had been found among the individuals who took Truvada as prescribed in the research trials.

Despite these outstanding outcomes, it was still anticipated that the regimen would not protect all individuals, even when taken as prescribed. As Robert Grant, M.D., M.P.H., principle investigator of the iPrex study, reminded us: "PrEP is highly effective when used, although there is no guarantee that PrEP will work all the time. We do not make guarantees in medicine, and after 30 years working in HIV research and clinical care, I have learned to 'never say never.'"

More than six years after the FDA approval, we do have a small number of cases worldwide where people using PrEP have contracted HIV. Researchers are seeking to learn from these cases and gain insights into how PrEP can most effectively be used.

Importance of Getting HIV Tested Before Starting PrEP and Going Forward

The updated 2017 PrEP guidelines published by Centers for Disease Control and Prevention (CDC) offer a protocol of medical and ethical best practices for offering and prescribing PrEP. Of great importance is the guideline that you are confirmed HIV negative through an antigen and/or antibody HIV test before starting PrEP. In some cases, a provider may wish to do an additional test 30 days after starting PrEP. Both of these tests are there for your protection, as starting PrEP while already having HIV could result in developing a strain that is harder (or resistant) to treat.

It is recommended that you use PrEP daily while you are at risk of acquiring detectable HIV. Your provider will likely ask you to be tested for HIV every three months, as well as to receive screening for syphilis, gonorrhea, and chlamydia quarterly (or more often if needed).

When getting tested for sexually transmitted infections (STIs), you will most likely be offered a swab in your throat, your rectum, your vagina. People with penises will be asked to submit a urine sample. This is called "multi-site testing," which maximizes the identification of infection in any of the sites where STIs can be found. Multi-site testing is done because an STI in your rectum would not show up in urine or in other areas, thus with limited testing it would not get properly treated.

Additionally, every six months, your prescriber will order a blood test to monitor kidney functioning. This may sound like a lot of work, but all of these tools exist so you can use PrEP as safely and comfortably as possible while minimizing any potential risk for you and your partners.

How Can Providers Tell Someone Is Taking PrEP as Prescribed?

There are ways a provider can explore whether you're taking PrEP as prescribed. In most cases, they will simply ask you about taking your medication and any obstacles you may have to using it consistently. Some research trials and clinical demonstration projects use methods such as measuring pill counts in bottles, tracking pharmacy refills, and testing blood plasma. The newer technology of dried blood stain (DBS) testing, which first became available in 2011, allows researchers to see a timeline of adherence going back four to eight weeks. Even newer advances in hair analysis can show a time of adherence going back approximately 90 days. Although DBS tests and hair analyses are not commercially available, they can be accessed through an ongoing study at University of California, San Francisco. The SERO PrEP Initiative is a resource provided by Grant's laboratory for people who may have become HIV infected after receiving PrEP, and it offers confirmatory lab tests and other services free of charge.

When providers and patients follow established protocols, meet with each other regularly, and communicate openly and honestly, then PrEP can play a significant role in lowering HIV rates among individuals, groups, and larger communities. But exactly how well does it work, and why does it occasionally fail?

At least 463,000 individuals are now using PrEP worldwide, according to the March 2019 Global PrEP Tracker report, and only three incidents have been reported where individuals with verified adherence to the drug acquired HIV. Three additional cases have been reported with unconfirmed adherence, and three are currently under investigation. TheBody intends to be a fact-based resource for empirically driven research updates as they become available in these cases and for additional reports in the future.

Cases of Seroconversion on PrEP With Verified Adherence

  1. Location: Toronto, Canada
    Gender: Cisgender male
    Publicly reported: February 2016
    Received resistant strain? Yes
    Adherence confirmed by dried blood stain (DBS) test? Yes
    Description: A 43-year-old gay man seroconverted after two years on PrEP. Dried blood spotting tests demonstrated greater than adequate adherence at the time of seroconversion. His strain suggested that he acquired a virus resistant to the same medications found in the drug Stribild (elvitegravir/cobicistat/FTC/tenofovir).
    Read more in this article on TheBodyPro.

  2. Location: Amsterdam, Netherlands
    Gender: Cisgender male
    Publicly reported: February 2017
    Received resistant strain? No
    Adherence confirmed by DBS? Yes
    Description: A 50-year-old gay man in a PrEP demonstration project seroconverted HIV eight months after starting PrEP. Dried blood spotting tests demonstrated greater than adequate adherence at the time of seroconversion. He did not acquire a strain of HIV that is resistance to medications.
    Read more in this article on TheBodyPro.

  3. Location: California, United States
    Gender: Cisgender male
    Publicly reported: October 2018
    Received resistant strain? Yes
    Adherence confirmed by dried blood stain (DBS) test? Yes, as well as hair sampling
    Description: A 21-year-old Latinx man acquired HIV between months 10-13 of using PrEP. He had been confirmed as HIV negative at initiation, as well as months 3, 6, and 10. Through hair sampling it was verified he had more than adequate adherence from the previous 6 months. His strain of HIV was resistant to the same medications as his primary partner. His viral load was quickly brought down to undetectable.
    Read more in this article on TheBodyPro.

Cases of Seroconversion on PrEP Without Verified Adherence

  1. Location: Kenya or Uganda, Africa
    Gender: Cisgender male
    Publicly reported: January 2015
    Received resistant strain? Yes
    Adherence confirmed by DBS? No
    Description: Age unknown of a heterosexual man who was a participant in the PARTNERS PrEP trial. His strain contained virus variants with M184V, which is resistant to Emtriva (emtricitabine, FTC). Adherence could not be confirmed given dried blood spotting was not yet available, and "blood plasma is a poor indicator of adherence, no one can say how many tablets were used per week, only that at least one tablet was used in the days before each clinic visit." Also, "tenofovir [Viread] levels were assessed only every 3 months, and thus missed doses and intermittent use cannot be ruled out."
    Read the full study published in the Journal of Infectious Diseases.

  2. Location: New York, United States
    Gender: Cisgender male
    Publicly reported: October 2016
    Received resistant strain? Yes
    Adherence confirmed by DBS? No
    Description: A gay man in his 20s tested positive for a multi-resistant strain of HIV four months after initiating PrEP on Jan. 1, 2016. Adherence at the time of HIV acquisition could not be verified due to missed doctor appointments. Dried blood spotting and hair sampling submitted on June 9, 2016, confirmed strong adherence to PrEP 30-60 days prior, but this sample did not cover the window of time in which he is believed to have acquired HIV (either February or March 2016).
    Learn more in this webcast of a presentation on the case at the 2018 HIVR4P conference.

  3. Location: North Carolina, United States
    Gender: Cisgender male
    Publicly reported: March 2018
    Received resistant strain? Yes
    Adherence confirmed? No
    Description: A 34-year-old gay man tested positive for a multi-resistant strain of HIV 13 months after initiating PrEP in February 2016. He was not confirmed as HIV negative before initiating PrEP. He admittedly stopped using PrEP for 61 days on his own (May-July 2016), then restarted, all without any confirmatory testing. Dried blood spotting and hair sampling was taken at the time of his first HIV-positive result on Apr. 17, 2017, and confirmed strong adherence to PrEP in the 90 days prior. But no monitoring or HIV testing took place between February 2016 and January 2017, and therefore, "We can't really tell if he was infected with a multi-drug resistant (MDR) virus (making this a PrEP failure) or whether resistance emerged on ongoing two-drug PrEP after HIV infection had already occurred."
    Read more in this article on TheBodyPro.

  4. Location: Pattaya, Thailand
    Gender: Cisgender male
    Publicly reported: June 2018
    Received resistant strain? Yes
    Adherence confirmed? Yes, adherence was confirmed for the last 6 of the 8 weeks the patient used PrEP but his HIV status at time of initiation is uncertain.
    Description: A 28-year-old cisgender man initiated PrEP on March 16, 2016, at the same time a third-generation HIV antibody test showed HIV negative results. Further third-generation HIV anitbody tests showed HIV negative on April 22 and May 13. However, an RNA test on May 13 revealed an HIV-positive result which was soon confirmed. As third-generation antibody tests have a window period of three to twelve weeks, the actual timeline of seroconversion cannot be determined, and it is unknown if he was actually HIV negative at the time he began using PrEP.
    Read more in this article on TheBodyPro.

  5. Location: Sydney, Australia
    Gender: Cisgender male
    Publicly reported: March 2019
    Received resistant strain? No
    Adherence confirmed? No
    Description: A 27-year-old cisgender man self-reported that he acquired HIV while using the "on-demand" (or intermittent dosing) schedule. One of the doctors advised on the case shared, "I don't think we can say that we know how he acquired HIV, or even when he acquired it." No further evidence or facts are known.
    Read more in this article I wrote for Plus.

Cases Under Investigation

  1. Location: Melbourne, Australia
    Gender: Cisgender male
    Publicly reported: May 2017
    Received resistant strain? Unknown
    Adherence confirmed? Unknown
    Read more in this article on the Australian media site SBS.

  2. Location: North Carolina, United States
    Gender: Cisgender male
    Publicly reported: January 2018
    Received resistant strain? Yes
    Adherence confirmed? Unknown
    Read more at PrEPFacts, a large Facebook group I manage.

  3. Location: Washington state, United States
    Gender: Cisgender male
    Publicly reported: March 2018
    Received resistant strain? Yes
    Adherence confirmed? Unknown
    Read more in this article on Public Health Insider.

If you or your provider believe you have acquired HIV while adhering to PrEP, please contact the researchers at the SERO PrEP Project so they can learn more from your experience and offer their treatment advice. It also advisable for your doctor to report your case promptly to your country's drug regulatory agency (in the U.S., the FDA) and to Gilead, the manufacturer of Truvada. The more people communicate, the more we will understand.