PrEP Resistant HIV: One-Off Case or Shocking Reality?

Truvada fails in a smaller group of the population commonly known as MSM. Recently, these cases have been more and rarer but not fully ruled out. It’s a shocking reality but something not to be feared. Still, Truvada provides protection up to 99% or more for an individual following the drug’s prescription.

It’s time to get understand the root reasons for acquiring HIV even with a committed PrEP prescription. At HIVPrEP, we explore this condition with an amiable discussion to let you know how to use the PrEP medication as well as what preventive measures to consider while using the PrEP drug.

💊When Is It Recommended to Take PrEP Medications?

It’s good to know that PrEP is prescribed to be used with other safe sex methods. A condom is the most recommended strategy to be used along with PrEP tabs when engaging in sex with a partner with unknown HIV status or when you are at a high-risk exposure for virus acquisition. Condoms can further decrease the risk of HIV.

Is PrEP right for you? Tenofovir/emtricitabine is a drug combination with the brand name Truvada. It’s a daily pill prescribed for individuals who are at very high risk for HIV. These medications lower the chances of getting infected by stopping the virus from taking hold and multiplying in your blood cells [1].

It’s prescribed for:

  • HIV-negative individuals engaging in sexual activity with an HIV-positive partner;
  • gay or bisexual/heterosexual people regularly practicing condomless sex, particularly with partners of unknown HIV status who are at an increased risk for virus infection;
  • individuals who inject drugs and have shared needles in the past 6 months.

PrEP meds are highly effective for preventing HIV, providing a protection level up to 99% (or more than 70% for individuals who inject drugs) if used as prescribed. On the contrary, the same drug is much less effective if not administered consistently or as prescribed.

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🎗PrEP Resistant HIV Strains: Research Studies

There are a few known incidences where PrEP HIV resistant (virus-resistant) to the use of tenofovir/emtricitabine. Very few men acquired the virus while on the PrEP medication with Truvada – even while adhering to the dose prescription as proven from the three test samples of hair and dried blood spots.

With enough scientific evidence to conclude this, a man can contract the virus not only because he didn’t take PrEP (TDF/FTC) as prescribed, but because some strains of virus acquisition are resistant to the two antiretroviral medications in Truvada – TDF/FTC. There is an example of two men who contracted the virus while in full compliance with Truvada [2].

Performing a sexual act with a person who has a fully suppressed virus (viral load) is virtually uninfectious. But some men can get the infection even in such conditions. This is most evident in MSMs contracting HIV from condomless sex while on PrEP (in perfect adherence to the daily Truvada regimen).

Drug resistance can happen due to multiple resistance mutations (cross-resistance), including the use of Truvada’s tenofovir and emtricitabine medicines. As a matter of fact, this condition of having a virus that is resistant to both of the antiretrovirals existing in tenofovir/emtricitabine is extremely rare.

From the research done by CROI 2018 based on King County, 0.3% (only 12 people) of the total sample population of 6,963 has high-level resistance to both the medicines in Truvada [3]. That means this percentage contracted virus not because of non-adherence but due to the fact that the virus was resistant to both emtricitabine and tenofovir.

Another study in macaques depicts that the tenofovir-resistant virus but not the emtricitabine-resistant virus can lead to a breakthrough virus infection despite the two-drug combination (TDF/FTC) for PrEP. FTC resistance with M184V/I occurs more frequently than TDF resistance with K65R in seroconverts [4].

🔍Is It a Prevailing Problem?

Even though developing resistive strains of virus acquisition can occur while using the two antiretroviral medications in Truvada – TDF/FTC, there have also been rare but confirmed cases where an individual acquired the infection while on the full drug prescription.

There is evidence of individuals who acquired the virus even with full adherence to PrEP. One is from New York City and another – a 43-year-old Canadian. Both men are in the MSM category [5].

There are also other studies that show cases of this rare PrEP failure including a man from California. Others having been observed in North Carolina, the Netherlands, and Thailand. And maybe there are other cases not known to clinicians [6].

As there are cases arising rarely, this condition is prevailing. Although the benefit of preventing HIV-1 virus infections with FTC/TDF PrEP far outweighs the possible risk of drug-resistant acquisition, we should not fear virus resistance from this drug for PrEP.

It’s important to administer PrEP only if you have been fully proven to be HIV- negative. Drug resistance is something that’s strange and if detected earlier, there is a possibility to prevent the spread of HIV-1 resistance to TDF/FTC.

📌Tips to Minimize the Risk of HIV Drug Resistance

The first step to take before starting PrEP is to make sure you are confirmed HIV-negative. Adherence to the drug’s prescription is a must. In most cases, resistance to PrEP drugs is only a risk if you are infected with the virus.

To ensure you conform to PrEP standards, an individual is supposed to test for HIV every three months in order to receive a new PrEP prescription.

Although it is required to consistently take PrEP, a person may contract HIV-1 during a break from PrEP and from not testing their HIV status prior to restarting Truvada medication.

When a person misses too many FTC/TDF doses (inconsistent taking of the drug), it may contribute to low levels of Truvada’s active substance in the body making it ineffective to fully prevent virus acquisition. In this case, the continual exercise of unprotected sex may make the virus escape the protection and finally infect the blood. Continual use of PrEP while being infected may develop virus resistance to ARV.

TDF/FTC is the only approved medication for PrEP. Although there exist drug-resistant strains of HIV, they’re very rare. Truvada still remains highly effective for both PrEP and ART.

The WHO is raising awareness and a program is active until 2021 to prevent, monitor, and effectively respond to the emergence of HIV-1 drug resistance [7].


  1. Is TRUVADA for PrEP® right for me?
  2. Second Man Contracts Rare HIV Strain While Adhering to PrEP. Benjamin RyanRetrieved October 19, 2016.
  3. How much ‘PrEP-resistant’ HIV is out there? Gus Cairns. Retrieved 09 March 2018.
  4. Should We Fear Resistance from Tenofovir/Emtricitabine PrEP? Urvi M. Parikh and John W. Mellors. Current Opinion in HIV and AIDS. 11(1):49–55, Jan 2016.
  5. PrEP Fails in Gay Man Adhering to Daily Truvada, He Contracts Drug-Resistant HIV. Benjamin Ryan. Retrieved February 25, 2016.
  6. Sixth case of rare PrEP failure reported—here’s what to know. Emily Land. Retrieved October 5, 2018.
  7. HIV drug resistance.
Logan Morris

Expert in pharmaceutical practice and antiviral medicine, founder of HIVPrEP. Main goal is to popularize HIV topics and create awareness for global masses on how to prevent the disease and how to use HIV medication safely.

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