'Curiosity About Any Failure of PrEP Is Healthy Because It Is So Extremely Rare'

An Interview With Robert Grant, M.D., M.P.H., on the New Case of HIV Acquisition by an Adherent PrEP User

Robert Grant, M.D., M.P.H.
Robert Grant, M.D., M.P.H.

Two documented cases of a person acquiring HIV despite consistent use of pre-exposure prophylaxis (PrEP) now exist, with news of the second incidence announced at the 2016 HIV Research for Prevention conference in Chicago. Yet, top HIV prevention researchers, clinicians and advocates are emphasizing that PrEP remains an excellent strategy.

TheBody.com's prevention expert Damon L. Jacobs interviewed Howard Grossman, the doctor (and PrEP user) who cared for this patient and diagnosed his HIV infection.

Then he turned to Robert Grant, M.D., M.P.H., lead investigator for the pivotal iPrex study that first confirmed PrEP's high level of efficacy. He asked Grant to summarize this new case within the context of expanding PrEP use four years after its FDA approval and during an era of increasing knowledge and hope about HIV prevention. Grant also shared that he is working with colleagues to develop a protocol that will track people who experience the very rare event of acquiring HIV while on PrEP.

How would you summarize this second case of someone getting HIV while adherent to PrEP?

This situation appears to be a transmission to someone who was using PrEP and that the virus has some resistance to both components of PrEP: tenofovir and emtricitabine [Truvada]. The good news is that his viral load remained very low and he is doing well on therapy.

I congratulate everyone involved for staying curious, getting the needed history and specimens, and doing the lab analysis.

We now know of two individuals who acquired HIV while adhering to Truvada as PrEP. Based on these two cases out of at least 100,000 PrEP users to date (as estimated by Dr. Howard Grossman), would you still say that daily PrEP reduces an individual's chance of acquiring HIV by 99%?

At least 99%.

How common are the mutations that have overcome PrEP in these two cases out of likely millions of sex acts?

These mutations can occur in 20% to 60% of people who have a sustained viral rebound to a first line regimen containing emtricitabine and tenofovir. Yet most transmission occurs from people who are HIV undiagnosed or who have left medical care entirely. Among these groups, resistance to both emtricitabine and tenofovir is rare -- especially when we consider that, in the absence of therapy, such resistance falls to low archival levels. Such archived viral variants are typically not transmitted.

Is it sufficient for people on PrEP to use standard HIV testing?

Yes. Acquiring HIV infection is extremely rare among people who are taking PrEP as prescribed.

There are multiple advantages to more sensitive HIV tests. RNA testing is more sensitive than antigen testing, which is more sensitive than antibody testing on blood, which is more sensitive than antibody testing on saliva.

The advantages of more sensitive HIV testing include making an HIV diagnosis earlier, getting people into therapy sooner and getting better counseling about HIV status. Monitoring PrEP with more sensitive tests also has the advantage of early detection of the few rare infections that occur, especially among people who struggle to use PrEP consistently.

Yet, any HIV test is enough. I prefer to focus on finding ways to make getting and using PrEP and HIV treatment easier. Any test is good enough.

Based on this second case, will you be changing how you talk about PrEP?

I will continue to say that using PrEP is protective against getting HIV and there are no guarantees. The feeling of safety fostered by PrEP has been healing for so many people and that should be celebrated. When HIV infection occurs, it can be treated with excellent responses. This is an opportunity for us all to rethink our fears and celebrate our human connections, with or without HIV.

What would you advise providers to tell their patients who are on PrEP and now afraid it won't work?

Infection during PrEP use is rare. If infection occurs, it can be treated. In the absence of PrEP, HIV infection is much more common.

For many people, fear of HIV is driven by fear of rejection. This is a good opportunity for providers to learn about HIV treatment: that it prolongs and enhances life and that it is easier and safer than ever before. We should make sure that people know that effective treatment makes sex with partners safe.

Why are these very few cases of infection while on PrEP getting so much attention?

Early adopters want guarantees. I think curiosity about any failure of PrEP is healthy, because it is so extremely rare.

There are also some anti-PrEP attitudes that are rooted in investment in other prevention strategies, fear of intimacy, homophobia, fear of disruption and trauma. These processes are expected and call for open and compassionate discussion.

With colleagues, I am developing a protocol that will facilitate prompt evaluation of people on PrEP who are suspected to have infection. I expect to have institutional review board approval in a month.

This interview has been lightly edited for clarity and length.