PrEP has first failure

Timothy Kincaid

February 25th, 2016

There has always been the assumption that a person on pre-exposure prophylaxis could become infected with HIV if they had sexual contact with a person who had a large viral-load of a strain of HIV which was resistant to each of the drugs in Truvada. Now there is a documented case. (Poz)

Researchers have for the first time documented a case of an individual contracting HIV, a multi-drug resistant strain, while apparently adhering well to the daily regimen of Truvada (tenofovir/emtricitabine) as pre-exposure prophylaxis (PrEP). The scientists concluded that it is indeed possible for individuals who are adherent to PrEP to contract HIV when they are exposed to a virus that is resistant to both drugs included in Truvada.

While this case is concerning, experts in the PrEP field suggest that such failures of PrEP will likely remain rare.

There have been strains of HIV identified which are resistant to tenofovir and strains resistant to emtricitabine, but random sample testing has not, until now, identified any strain which was resistant to both. Such virus is very rare.

An HIV strain may become resistant to a medication if the person infected uses medication in a sporadic manner allowing the virus to combat low levels of the medication until mutations occur. This person had a virus which was resistant to several medications.

While this is only one case out of tens of thousands of PrEP users (each of whom is tested quarterly) highlights the importance of using PrEP as an added layer of protection, not as a magic bullet.

Priya Lynn

February 25th, 2016

“While this is only one case out of tens of thousands of PrEP users (each of whom is tested quarterly) highlights the importance of using PrEP as an added layer of protection, not as a magic bullet.”.

Thanks for telling it like it is.


February 25th, 2016

Countdown for AHP to declare victory???


February 25th, 2016


Just want to point out, it’s AHF not AHP. But, it will probably be by tomorrow that Weinstein will be doing a victory lap about how this proves just how right they were all along. What’s kind of funny is if you type in “AIDS healthcare foundation” the second suggestion that comes up mentions PrEP.

enough already

February 26th, 2016

I regret this man becoming infected. That he received treatment so quickly is a part of PrEP.
Nothing about this changes the fact that this cocktail is making inroads against the spread of HiV enormously faster and tremendously better than those awful condoms ever did/have/could/will.

Priya Lynn

February 26th, 2016

“Nothing about this changes the fact that this cocktail is making inroads against the spread of HiV enormously faster and tremendously better than those awful condoms ever did/have/could/will.”.

I’m not so sure about that given the tremendous cost of the drug. Also many taking it won’t be so consistant (particularly given its high cost) and this will lead to versions of HIV resistant to this drug over time as many have pointed out.

Timothy Kincaid

February 26th, 2016

Priya Lynn,

For most Americans with health insurance, there is no out-of-pocket cost. This is also, I believe, true in France.

You are correct that in Canada, PrEP is very expensive. And it may not make inroads there as quickly.

You are not correct, however, in believing that inconsistent use of PrEP can lead to drug resistant HIV strains. That’s not how it works.

HIV mutates only in the body of infected persons who are inconsistent in their medication. It does not mutate where it does not exist. PrEP users are, by definition, negative and test regularly.

Priya Lynn

February 26th, 2016

But Timothy, aren’t the two drugs that make up Truvada also used to treat people with HIV?

And wouldn’t it be possible for an inconsistent user to contract HIV, continue using Truvada, and cause the virus to mutate?


February 26th, 2016

HI Priya Lynn

That is a concern, and why one of the guidelines is to get an HIV test (often a larger STD panel) every 3 months, with discontinuance of PrEP if there is a positive test for HIV.

There was some studies on this, IIRC, and they ended up concluding that the benefit of reducing HIV infections was much greater than risk developing a drug resistant strain of HIV.

Timothy Kincaid

February 26th, 2016

yes it is possible that a person using PrEP inconsistently could seroconvert. But that would require some real inconsistency.

Some testing suggests that four days per week is nearly as effective as daily doses. So even if this PrEP user skipped every other day, they would likely not become infected.

Could this result in a mutated virus? I’m not sure. There appears to be one case in which this has occurred so it is at least possible. So I misspoke above.


February 27th, 2016

Timothy, there are recorded instances of people with undiagnosed acute infections when they started PrEP or who contracted HIV because of inconsistent adherence developing resistance to one or both of the drugs in Truvada. Fortunately it is rare and, remarkably, the resistance disappears after the use of Truvada is discontinued.

A study on what happens when Truvada is stopped was published last year and is covered by aidsmap here. From the article:

“Drug resistance acquired in rare cases of HIV infection during treatment with pre-exposure prophylaxis (PrEP) rapidly disappears once medication is discontinued, investigators report in AIDS. Use of ultra-sensitive tests performed six months after seroconversion and discontinuation of PrEP failed to find any resistant virus.”

As Oggbert wrote, concern about resistance is precisely why quarterly HIV testing is part of the protocol for the use of Truvada as PrEP. In addition Gilead is required to collect samples from anyone who acquires HIV while using PrEP to evaluate them for resistance.

Timothy Kincaid

February 27th, 2016

Werdna, thank you for the link and additional info

Priya Lynn

March 2nd, 2016

““Drug resistance acquired in rare cases of HIV infection during treatment with pre-exposure prophylaxis (PrEP) rapidly disappears once medication is discontinued…”.

You’d think they are honest and know what they’re talking about but that seems extremely unlikely to me.


March 3rd, 2016

I can see why it might seem surprising that resistance acquired due to the use of PrEP with an undiagnosed infection would disappear so quickly, but if you think about the evolutionary process by which resistance develops it actually makes a lot of sense.

Mutations appears when HIV replicates, but most of these mutations aren’t helpful and they typically make the mutated copies less fit to survive and reproduce. Exposure to the drugs in Truvada creates an evolutionary pressure conferring an advantage to copies with mutations that make them less susceptible to those drugs. The less-susceptible copies are more likely to survive and reproduce (even if they are overall less fit) and the ones that are more susceptible are less likely to survive. The longer this happens the more resistant copies there are in the viral pool. That’s how resistance develops.

In cases where people on PrEP acquire HIV they are likely to be diagnosed quickly because of the quarterly testing schedule. That means their virus hasn’t had much exposure to the drugs in Truvada so the proportion of their virus that has become resistant isn’t huge, that there’s still a fair amount of non-resistant “wild type” HIV in their viral pool.

Once you remove the drugs from the equation, the copies that have developed resistance have no advantage and the fitter wild type HIV will once again come to predominate because it’s better at reproducing. That’s what the study in AIDS found, that within 6 months the amount of resistant virus in the viral pool had fallen below the level that could be detected.

That’s obviously a fairly simplified version of how it works, but hopefully it makes sense.

Priya Lynn

March 3rd, 2016

Ummm, I don’t know… I’ve had a deep interest in and followed resistance due to pesticides, herbicides, anti-biotics, and anti-virals and that idea goes against everything I’ve learned. Even the researchers in the link you posted said that more research should be done. I find it implausible that resistance to Truvada should disappear with cessation of the drug, I think more likely there is a problem with the study itself and the handful of people looked at.


March 3rd, 2016

Priya Lynn –

This is not a particularly new concept in HIV studies.

Most mutations harm the ability of HIV to replicate more than help it – I believe that there are studies showing evidence that the K65R mutation and K65R+M184V mutation (both selected by either FTC or TDF, the drugs in Truvada) both have less replication capacity than non-resistant (“wild-type”) HIV. These resistant mutations are rather rare in the huge amount of testing that has been done, also indicating that there is no selective advantage to them (with out the pressure of medication), and it is more likely there is a selective disadvantage to them, or as werdna says, the are “less fit.”

If that is accurate, and the people in the study did not start treatment for several years (as indicated), it is likely that the wild-type (non-resistant) virus had a selective advantage over the mutations.

The question on research is that once treatment starts, will it be effective for as long as normal, or will a FTC/TDF resistant develop faster or more often than would be expected.

Priya Lynn

March 3rd, 2016

“Most mutations harm the ability of HIV to replicate more than help it “.

Not in all cases. Don’t ask me to believe something that is obviously wrong.

Priya Lynn

March 3rd, 2016

Whoops, missed the “most” part in Oggbert’s post.

Regardless, beneficial mutations do occur and are naturally selected for. You people can believe whatever you find the most desirable but you’re not going to convince me of this – it goes against everything I’ve learned about resistance to drugs.


March 3rd, 2016

Priya Lynn –

Fine, I’ll clarify for accuracy. Most mutations are probably neither harmful nor helpful. The mutations mentioned in the article that impact drug resistance to NRTIs like Truvada appear to have a selective disadvantage barring selective pressure from that class of drug.

I was able to find multiple studies showing the same thing as above. In one, people had stopped taking a NRTI (due to resistance), the drug resistant mutations (K65R and M184V) had all but vanished in testing after 10-30 weeks. In another (in lab tests, not people), the same thing occurred.

You may disagree, but these studies have been replicated multiple times and as far as I can tell, most scientists accept that the wild-type (non-resistant) strain of HIV reproduces best in the body and will out complete the mutations the article mentioned.

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