Like us, you’ve heard and read the accounts of guys testing positive for HIV while taking PrEP. Their stories are told inside bars and clubs, spread from person to person, but most of all, posted on the internet for all to see. They make sure to tell us that not only have they tested poz while using this medication, but they also know of “lots of other guys” who have had the same experience. These stories are told with such emotion and conviction that the casual recipient of this information believes it without a doubt. But there is one big problem with their tales; they are lies. Every single one of them is a liar. Yeah, we said it!
Since PrEP was announced as a medication to prevent the spread of HIV, it has lived in a home built on controversy and fearmongering. Truvada whores were our newest community villains, shy of those horrid Barebackers. PrEP detractors consider those who take this medication lazy party bois who want to have as much condomless sex as possible. The theory, which proved to be correct, is that the STD infection rate within our community would rise.
In reality, PrEP is most prescribed and recommended for those guys who are already known to have high-risk sex, including a lack of condom usage and multiple partners. Their use of PrEP leads to an increase in overall STD testing and treatment, which could explain the rise in infections reported.
The plain truth of the matter is PrEP works! It is 99% effective in stopping HIV infection through sexual intercourse. Anyone who tells you differently is a pure, simple, dirty, lying liar who lies. This is not to say that there are not those who have contracted HIV while using PrEP or that there are not some who honestly believe that they fall into this category.
When it comes to PrEP failure, there are two reasons. The first, and the most common, is user error. The second, which concerns most people, but is so rare that it should not, is PrEP failure.
So, let’s talk about what’s going on.
What is PrEP?
By now, you should know what PrEP is and how it works, but if you don’t, click here for more information. For this article, you need essential information about the two medications that make up the formula for PrEP. These would be emtricitabine and tenofovir. Together they are more commonly known under the brand name Truvada. In 2012, it became the first drug approved by the Food and Drug Administration to prevent HIV-negative people from contracting HIV through sexual intercourse. These medications have been used separately and together to fight HIV infection in those living with the virus for much longer. So, no, PrEP is not a new medication, and it has been highly tested and proven, over and over again, by multiple agencies across the globe.
Humans are imperfect creatures that make mistakes and errors; sometimes, these are small and easily corrected, and sometimes, they have a much larger footprint. Once we agree that guys are human and will make mistakes when prescribed PrEP, failure on this medication makes more sense.
The two most common dosing for PrEP is once daily and so-called On Demand Dosing, where the individual takes the medication before and after sexual contact, which is growing in popularity. Both have the same effectiveness in preventing HIV infection, and the differences are more about diminishing user error and addressing possible side-effects and cost concerns.
To be very clear, PrEP is just like any medication. If you do not take it EXACTLY as your doctor prescribes, you will not receive the product’s full benefits as the manufacturers intended and tested for. This would not be the fault of PrEP but of the guy using it, and this is the case with almost every single person who has contracted HIV while “on PrEP.”
Along with individual user error is something we call “systemic breakdown.” This is when the error occurs not just with the user but also with the established protocols for ensuring the person being prescribed PrEP is the correct candidate and follow-up prescribing and testing are conducted. In effect, the doctors can fuck up too.
Because HIV is not like any virus we have encountered, our treatment and prevention methods must also be new and innovative. PrEP is designed to prevent HIV from entering healthy cells. But, to work efficiently, those cells must be free of HIV in the first place. To address this need, protocols have been created to reduce ineffective treatment and drug resistance cases.
The CDC has developed guidance for providing PrEP to those most at risk for HIV infection. (SPOILER ALERT: THIS INCLUDES YOU).
Screening is the first phase in the delivery of PrEP. The screening phase includes the steps of engagement, navigation, and an initial clinical evaluation. Screening is often the most time-intensive phase within the PrEP Care System.
- Engagement includes an HIV risk assessment to identify persons who may benefit from PrEP. It also provides education about PrEP basics, including how PrEP works, the importance of medication adherence, and medication side effects.
- Navigation services should be offered at the time of PrEP engagement to guide persons in need of PrEP to clinical services and insurance options that will pay for PrEP. If the client does not have insurance, navigators or clinic staff should assist the client in obtaining insurance or accessing medication assistance programs.
- The initial clinical evaluation is the final step in the screening phase and is performed by a medical provider. It occurs before prescribing PrEP and includes a brief history, including signs or symptoms of acute HIV or sexually transmitted diseases (STDs), history of kidney disease, a medication review, and an assessment of indications for PrEP. The provider also should conduct an HIV blood test, evaluate kidney function, check hepatitis B virus (HBV) and hepatitis C virus (HCV) serology, and test for STDs.
II. PrEP Initiation
Where the initial clinical evaluation is an assessment of indications for PrEP, including a review of laboratory values, PrEP initiation refers to when the PrEP medication is prescribed.
For locations where laboratory testing results, including an HIV test, are available on the same day as drawn, the initiation phase may occur on the same day as the initial clinical evaluation. When it is impossible to rule out HIV and normal renal function on the same day as the initial clinical evaluation, it is recommended to initiate PrEP within seven days of the HIV test to minimize the risk of HIV acquisition between the time of HIV testing and PrEP initiation. The U.S. Public Health Service’s Preexposure Prophylaxis for the Prevention of HIV Infection in the United States – 2017 Update pdf icon[PDF – 2 MB] provides additional instruction on ruling out HIV infection before starting PrEP.
At the time of PrEP initiation, PrEP basics are reviewed, and PrEP medication is prescribed. Medication can be provided directly by the clinic or a prescription to an outside pharmacy. Paying for PrEP is part of this phase, and some insurers may require prior authorization to cover the cost of medication or services. Medication can be accessed through drug assistance programs, like Ready, Set, PrEPexternal icon. Ready, Set, PrEP provides medicine for those without drug prescription coverage or insurance.
According to PrEP clinical practice guidelines:
- Every three months:
- Conduct HIV blood test
- Conduct a symptom review of STDs, acute HIV infection, and side effects
- Conduct HIV risk behavior assessment
- Screen for STDs in sexually active adults and adolescents with signs or symptoms of an STD and in men who have sex with men (MSM) at high risk, defined as those with a recent bacterial STD or those with multiple sex partners
- Provide adherence counseling and answer questions
- Provide a new 3-month prescription for PrEP
- Every six months:
- Screen for STDs in sexually active adults and adolescents who do not meet the criteria for more frequent screening
- Assess kidney function
A systemic breakdown can occur at any point during the above practice guidelines, but most often, if it occurs, it will happen during the screening process or one of the follow-up visits. Both will involve not discovering that the guy has been infected with HIV at some point before initial usage or a self-prescribed break in use. For example, The BodyPro published the case of a 34-year-old gay white man in the U.S. who received an HIV-negative result from an antigen/antibody test, which has an average window of 21-28 days.
Two months (or 62 days) after receiving these results, the man’s doctor gave him a 30-day prescription for tenofovir/emtricitabine, with 11 refills. No further confirmatory testing was conducted to ensure that the man had not acquired HIV during the unknown three-month window (November 2015-February 2016) or after initiating PrEP.
The man reported discontinuing use in May 2016 “due to perceived lack of risk,” then restarted on his own two months (61 days) later. At no point in this process was he ever tested for HIV, nor did he receive any monitoring from his provider. His HIV status and adherence patterns are undocumented during this entire seven-month period.
When PrEP does really fail
Nothing in life is perfect, including medications. For this reason, no doctor or scientist would ever claim that one is 100% effective. PrEP, when used correctly, is as close as we will most likely ever get. But, let’s dive into that possible 1%.
Just like a car that overheats, scientists have found that there is a limit to PrEPs’ ability to fight off HIV infection. The bar is crazy high, but one guy did fly over it.
A man in Amsterdam contracted HIV despite reporting excellent adherence to daily oral pre-exposure prophylaxis (PrEP) using tenofovir/emtricitabine (TDF/FTC, Truvada), according to a study presented at CROI 2017 in Seattle.
“A 50-year-old MSM (man who has sex with men) became HIV positive eight months after starting PrEP. The patient tested negative for HIV at the start of PrEP, at one month, three months, and six months.”
“The patient reported an average of about 50 anal sex partners per month before diagnosis, and he also reported having condomless anal sex on about 50% of the days before diagnosis. The median number of sex partners per day with condomless anal sex ranged between two to five each month. Additionally, during his time on PrEP, the patient experienced two instances of rectal gonorrhea and one instance of rectal Chlamydia. He also reported using drugs during sex, including amphetamine, cocaine, mephedrone, and ketamine.”
“The presence of an aberrant immune response under appropriate serum TDF levels raises the possibility that a very high HIV exposure, possibly in combination with inadequate TDF levels in the gut mucosa, may have led to infection,” the researchers hypothesize. However, it remains unknown why and how the patient seroconverted.”
“This underscores the importance of regular HIV testing in PrEP users and being aware of potential atypical seroconversion patterns,” the study authors conclude.”
Dried blood spots were collected at months six and eight, both of which showed adequate levels of tenofovir, suggesting good adherence to PrEP.
Unverified PrEP adherence
Contrary to PrEP detractors (READ: haters), there are many protocols to address medication adherence issues and procedures to quickly assist anyone believed to have contracted HIV while using the medication.
The SERO PrEP Initiative is a resource Grant’s laboratory provides for people who may have become HIV infected after receiving PrEP. It offers confirmatory lab tests and other services free of charge. At least 650,000 individuals are now using PrEP worldwide, according to the August 2020 Global PrEP Tracker report, and four incidents have been reported where individuals with verified adherence to the drug acquired HIV. A few additional cases have been reported with unconfirmed adherence or are currently under investigation.
As discussed earlier, adherence to PrEP is critical to receiving the most significant intended benefits and outcomes. But not everyone, for whatever reasons, can do so. When this happens, HIV infection can occur. That is not the end of the story, though. Once the infection has been confirmed, medical providers assess the situation and, if necessary, the individual’s full details and accounts will lead to greater study and research.
In the most basic terms, what this means is that if your friend, who claims to have contracted HIV while on PrEP, had done so while adequately using the medication as directed, he would have become one of the very rare case studies presented to the world at one of the yearly Conferences on Retroviruses and Opportunistic Infections (CROI). If not, he was one of the guys who failed while on PreP but was NOT failed BY PrEP.
Like in every area of life, there are outliers and those who fall into a grey category. Regarding PrEP, these will be individuals who converted to HIV positive while using PrEP but their faithful adherence can neither be confirmed nor invalidated.
As of the beginning of 2021, there are seven (7) cases worldwide, and the history of PrEP usage falls within this framework. You can read about them HERE. What they all have in common is the inability of doctors/scientists to pinpoint either the exact period of infection, the amount of HIV within the user’s system at the time of infection, and/or the veracity of the statements made by the user regarding his adherence to PrEP.
At this time, three (3) cases were reported to have been due to PrEP failure informally that are either unconfirmed or under investigation.
Verified PrEP adherence
Yes, we know; this is the information you truly care about. How many millions of guys worldwide have contracted HIV while on PrEP that the “lamestream media” refuses to report?
You are correct if you believe guys have been contracting HIV while using PrEP as prescribed. But, these numbers are not being hidden by anyone. On the contrary, each year, the numbers, if they exist, are reported in multiple outlets devoted to HIV infection and/or Infectious Diseases. It is essential that these stories be told and that we, as a community, understand the truth about PrEP. To be crystal clear, as of this writing, there have been a grand total of four (4) individuals in the entire world that have contracted HIV while having verified PrEP adherence. One of them, the gentleman from Amsterdam, was discussed earlier. The other three fall into the “resistance” category.
What is PrEP Resistance?
A 43-year-old gay man in Toronto adhered to pre-exposure prophylaxis (PrEP). Presented at CROI 2016 on Feb. 25, this is the first documented “PrEP failure” case. As reported by The BodyPro.
PrEP did not prevent infection in this instance because the person was exposed to a strain of HIV that had become resistant to several antiretroviral medications. These medications included (but were not limited to) tenofovir and emtricitabine, the two antiretrovirals in Truvada, which is currently the only PrEP regimen approved in the U.S.
It is estimated that well below 1% of people living with HIV are resistant to these two medications; even fewer also have a detectable viral load. Even if a person had this rare strain, if their viral load were undetectable, it would be extremely unlikely — borderline impossible, research has found — that they could transmit the virus to anyone.
Amount of PrEP resistance around us
Fearmongers will have you believe that PrEP resistance is common, but they would be lying. As published by AIDSMAP:
A study presented at the recent 25th Conference on Retroviruses and Opportunistic Infections (CROI 2018) aims to quantify how many people with HIV there might be in the community who both have a detectable HIV viral load and also have significant resistance to tenofovir and emtricitabine, the two drugs currently used in pre-exposure prophylaxis (PrEP).
The University of Washington in Seattle researchers found that in King County, which contains Seattle, no more than 0.3% of the local HIV-positive population had viral loads over 10,000 copies/ml and high-level resistance to tenofovir and emtricitabine.
However, an even smaller proportion of newly diagnosed people – just three cases in ten years, or one in 606 of those diagnosed – had primary drug resistance, i.e., actually became infected with tenofovir/emtricitabine-resistant HIV, and this is more likely to reflect the maximum frequency of people who could acquire drug-resistant HIV from someone else despite being on PrEP.
Susan Buskin and colleagues from Public Health Seattle and the University of Washington searched through drug resistance test records from 2003 to the end of 2017 to establish the frequency of high- and low-level resistance to tenofovir and emtricitabine. They also did four rounds of tests in 2016 and 2017 to establish how many people had “substantial” blood viral loads (viremia) of over 10,000 copies/ml and how many had low-level viremia of 1000-10,000 copies/ml.
They then counted how many people had both viremia and drug resistance together and used sequential testing to see how many had persistent viremia.
Out of 6963 people on King County’s database diagnosed with HIV, 3881 (56%) had a drug resistance test. Of these, 246 (6%) had high-level tenofovir/emtricitabine resistance, while at the last round of viral load tests, 310 had significant viremia or roughly 5% of people diagnosed. More news from the United States
However, only 12 people (0.3% of those with resistance tests, or one in 323) had both high-level resistance and significant viremia.
What about those who are undiagnosed with HIV?
If you are sexually active, you need to have regular tests for STDs, including but not limited to HIV. We recommend every three months. In the United States, a significant portion of people living with HIV are undiagnosed. These people do not know about their infection, so their ability to pass it on to others is very high, especially when they have been initially exposed. This is because HIV viral load counts are usually the highest, and thus most contagious, during this time frame because the body has not yet created antibodies to fight the virus.
About 1.2 million people are living with HIV in the US, but about 240,000 don’t know they are infected. Each year, about 50,000 people get infected with HIV in the US. As of 2017, the latest figures available and published by the CDC, 51% of those Americans known to be living with HIV DO NOT HAVE AN UNDETECTABLE VIRAL LOAD and are thus still able to transmit the virus. These figures are significantly higher than in comparable first-world nations.
Effectively, we are looking at three (3) issues, not one. First, those people who do not know that they are living with HIV, then those who do know but have not reached undetectable levels, and finally, of the prior two categories, how likely are they to have a strain of the virus that is resistant to PrEP?
The bad news
We don’t know what we don’t know. We can not research those who refuse to be counted. This is why it is imperative that we have the most significant number and percentage of our community tested for HIV and other STDs as often as possible, but also make sure that those who do test positive can have proper access to care and treatment as to become undetectable as quickly as possible.
The good news
Like in real estate, much of this information comes down to location, location, location. Whether you are in the United States, The European Union, Latin America, or Asia will dictate your possible exposure to HIV and your access to PrEP. More and more countries are finding ways to make the drug accessible and affordable to those most in need. Testing for HIV is increasing, and so is the knowledge about Undetectable equals Uninfectious (U=U). All of these measures are beginning to affect the HIV rates worldwide, but something new is being researched about PrEP usage that is worth noting.
In a symposium at CROI 2019, Jean-Michele Molina, MD, presented on PrEP failures, highlighting elements of diagnosis, resistance,+ and treatment.
“It’s an important issue to assess the relationship between PrEP failures and resistance. We’ve learned from clinical trials that the way to see a resistance emerging with PrEP is actually to stop PrEP in someone with acute HIV infection.”
We also know that there is a significant difference between someone developing resistance to PrEP while using it and someone encountering a sexual partner with a strain of the virus already resistant to the medications within PrEP. The former has yet to be experienced, and the latter is the form of infection we have seen.
Finally, every single person known to have contracted HIV while using PrEP, either verified or not, was placed on effective HIV treatment and is doing well. PrEP resistance does not result in those infected without medication treatment options or positive outcomes.
Before you Go
On so many levels, we have the ability to not only slow down the number of HIV infections but also the variant strains that are resistant to PrEP. Both involve getting tested regularly for HIV and, if positive, taking your medications correctly and as directed. Mutations come from those who are not consistent with their regimens.
With all of this being said, the most incredible power we have is spreading facts and not fear about HIV prevention, treatment, those who choose to take PrEP, and those living with HIV. The lies and disinformation circulating might seem funny and harmless, but 40 years of fighting this virus should teach us they are not.
If you or your provider believe you have acquired HIV while adhering to PrEP, don’t hesitate to get in touch with the researchers at the SERO PrEP Project so they can learn more from your experience and offer their treatment advice. It is also advisable for your doctor to report your case promptly to your country’s drug regulatory agency (in the U.S., the FDA) and Gilead, the manufacturer of Truvada. The more people communicate, the more we will understand.