Jean-Michel Molina, MD, on Biomedical Failures of PrEP: Rare, But Serious

March 12, 2019

In a symposium at CROI 2019, Jean-Michele Molina, MD, presented on PrEP failures, highlighting elements of diagnosis, resistance and treatment.

In a symposium presentation at the Annual Conference on Retroviruses and Opportunistic Infections (CROI 2019), Jean-Michele Molina, MD, chief of the Department of Infectious Diseases at the University of Paris, presented on PrEP failures and elements of diagnosis, resistance and treatment.

Contagion® sat down with Dr. Molina for an exclusive interview about his presentation and to discuss the rarity of PrEP failures, as well as the need to thoroughly investigate these occurrences.

Interview Transcript: (modified slightly for readability)

Contagion®: What are some reasons for PrEP failures?

Dr. Molina: There are multiple reasons for PrEP failures and they could be at any point in the PrEP continuum of care. From people who may not use their pills as recommended, to a health care system that is not able to provide access to PrEP for people in need, it could be also the physicians who are not ready to prescribe PrEP or not aware that they could use PrEP for preventing HIV in high-risk patients. It could be also the test that we use sometimes that are not able to detect acute HIV infection. And, if you start PrEP in someone with acute HIV infection you will see more resistance.

So, what we think when we talk about PrEP is the failure of drugs to protect against HIV acquisition. But in fact, what we call biomedical failures, so the failures of drugs, are very rare. We only have a few cases that be reported of real PrEP failures and even those cases raise questions about were they really failures of the drugs or failures to properly initiate PrEP in these people?

Contagion®: Can you explain the link between PrEP failures and drug resistance?

Dr. Molina: So, it’s an important issue to assess the relationship between PrEP failures and resistance. What we've learned from clinical trials is that the way to see a resistance emerging with PrEP is actually to stop PrEP in someone who has acute HIV infection.

Sometimes, in people at high risk, it is kind of difficult to rule out acute HIV infection, because the test we use might not be sensitive enough to diagnose acute HIV infection. That's why you may not rely only on serologic assay you probably need to do RNA assays, as well, and more importantly to repeat this test after starting PrEP so that you would avoid maintaining someone on PrEP if he's already infected with HIV.

We know that if you start PrEP on someone with acute HIV infection then you will see resistance emerging, probably in a high proportion of these individuals. When we look now at the emergence of resistance in people on PrEP for some time, so not at the first visit after PrEP initiation, but after a couple of months, then the emergence of resistance is quite low, because the failures of PrEP are more mostly due to failure to take drugs if you don't take drugs you're not going select for resistance.

Contagion®: What are some areas of PrEP failures and resistance that need to be explored in further research?

Dr. Molina: When we are using PrEP in real life it's not like in clinical trials when you have stored specimen and you could go back to the specimen and see you know what happened. With the failures that we're going to see in the clinic now, it's going to be more difficult to understand what was going wrong, and that's why you probably need to you know investigate these cases really deeply in terms of measuring adherence, looking for resistance, repeating the assays to really try to understand what was going on.

We have relied on PrEP as a very effective tool to prevent HIV acquisition. So, if this tool is failing we need to understand what failed. Is it the failure to take the drugs? Is it the failure of the drug themselves? And, that's why it is very important to understand these failures when they occur.