Anthony Fauci Traces the HIV Research Path to U=U

Anthony Fauci, M.D.
Terri Wilder

In the nearly 40 years since the discovery of HIV, probably no researcher has been more central to U.S. research than Anthony S. Fauci, M.D. And, as the director of National Institute of Allergies and Infectious Disease (NIAID), the International AIDS Conference is often a busy time for him. At this year's AIDS 2018 in Amsterdam, Fauci spoke to TheBodyPRO after his remarks to the U=U Preconference, in which he detailed the scientific research that lead us on the path to the discovery that undetectable equals untransmittable (U=U).

You can read Fauci discussing NIAID's research approaches to HIV remission and functional cure in part 1 of this conversation.

Terri Wilder: You gave a presentation at the U=U preconference.

Anthony Fauci, M.D.: I did.

TW: This was U=U: Celebrate, Activate, and Implement! You traced the science from the beginning up to the U=U messaging.

AF: Right.

TW: So, in light of everything that's going on in the world of HIV, where do you think that U=U fits into even the work that you do at the National Institutes of Health?

AF: The point that I made -- and I took a different approach. Because people say, you know, if you look at treatment as prevention (TasP), and you look at people whose viral load goes below detectable level in recent studies, that if you do prospective observational studies, you find out that tens and tens of thousands of condomless acts of sex are not associated with infection. Zero, really.

What I did with the audience is I said: "This didn't start in 2013. This actually started from the very, very beginning."

I started off with the fundamental concept of how easy is it, or how difficult is it, to transmit. And that was a few slides, which showed that, even prior to [antiretroviral treatment] (ART), prior to anything, this isn't an easily transmittable disease because the virus has to find an activated T cell, and that's not the easiest thing in the world.

When you look at the likelihood per exposure to get infected, even in a gay man, you know, it's like 38 per 10,000 exposures. In a heterosexual, insertive penile-vaginal intercourse, it's like four out of 10,000. That doesn't mean that we should be practicing risky behavior -- because there are 77 million people who've gotten infected and 36 million people living with HIV. But, inherently, this is not an easily transmittable virus like measles, which -- everybody gets measles when you walk in the room. Or like gonorrhea, which has got a high attack rate. So, I started there.

Then, I said, let's look at the pre-ART era. And in the pre-ART era, we've noticed on many studies -- and the first study that noticed that was from my group by a guy in my lab named Tom Quinn, who does work in the Rakai district of Uganda, who showed that, when he followed serodiscordant couples long before the era of ART, he found that the likelihood of transmissibility was directly related to the level of virus. So, if you had a high level of virus, you had a high likelihood of getting infected. If, just by natural control, you had a low level of virus, you have a very low chance. That was the pre-ART era.

Then, I went into the ART era and showed, even before you measured level of virus, just being on ART prior to sensitive assays for the virus, the people who were on ART had much less chance of transmitting virus to their sexual partner. That was on ART, but not measuring viral load.

Then, you graduate to the next level. When we were measuring viral load, it became clear that [with] people on ART, the lower the viral load, unquestionably, the lower the chance of getting infected.

And the final part of the talk was, let's look at people who have zero viral load -- namely, the HPTN 052 -- and look at what happens when you have partners followed over a long period and there is zero viral load.

That's when the data said no transmission. People didn't believe it. But if you put the data together, there were tens of thousands of condomless sex acts.

So, the next question is, ah! That's good for heterosexuals. Is it the same for gay men? Because they have a much greater incidence of getting infected. So, we did a study called PARTNER. And in PARTNER, there were heterosexual men, heterosexual women, and gay men. And if you looked at the gay men, they had zero transmissibility with condomless act.

But people said: "Well, you know, it's not the predominant study. It's only one-third of the study."

So, then we did a study called Opposites Attract -- purely gay men. Again, a few thousand condomless acts: zero.

Then, the big study that was just essentially presented today, PARTNER2 -- again, thousands of condomless sexual acts among just gay men [and] zero transmissibility.

So, if you look at the history from the very beginning to yesterday, when they presented PARTNER2, whether you're a heterosexual man, a heterosexual woman, or a gay man, if you have zero viral load, it's zero.

TW: So, zero is our word.

AF: Zero is the word. Right.

TW: This was a lot of information, and it's great that you were able to speak with us today.

AF: You know, one of the things that we should mention that I emphasized during my talk -- and it seems like a play on words, but it isn't -- [is that] even though zero really is undetectable, U=U when U really is you. Because there are some people out there who may think they are undetectable, and they're not. And they've got to be very careful. Because if you start on antiretroviral therapy, it isn't until you've been six months on therapy that you could be sure that you're undetectable. Because it generally takes a few months to get the viral load down to below detectable level. So, that's an important caveat.

TW: Thank you very much.

AF: You're welcome.

This transcript has been lightly edited for clarity.