Fauci: Countless Lives Have Been Saved, but an HIV Vaccine and Cure Remain Elusive

To mark the 25th anniversary of The American Journal of Managed Care^® (AJMC^®), we spoke with Anthony Fauci, MD, director of the National Institute of Allergy and Infectious Diseases (NIAID). Fauci has been at NIAID for 36 years, and he gave a keynote address at the first International AIDS Conference in San Francisco in 1990. Here he speaks on progress that has been made in the fight against HIV and AIDS, from AZT to Truvada to undetectable viral loads; why there is no cure just yet; and how the first tumultuous years of the AIDS crisis shaped research for decades to come.

AJMC^®: This year is the 30th anniversary of the International AIDS Conference in 1990. At the first meeting, you outlined the priority research gaps for the 1990s. If you look ahead, where are the remaining gaps? And what are you most excited about in terms of HIV and AIDS research, as well as other types of virus research?

Fauci: I think it’s important and appropriate to reflect back to that classic meeting in San Francisco in 1990 for a number of reasons, because it was between a time when the first drug AZT [azidothymidine] was approved in 1987 and [the time in] 1996, when we had the development of the triple combination cocktail, which has completely transformed the lives of HIV-infected individuals. So, what we were talking about then was the fact that we had treatments that seemed to help a bit. We were dealing with single and double drugs but not yet the famous “cocktail” that is now used where you can get a single pill that would contain 3 or more drugs—in most cases. So, it was a very interesting year.

It was the height of the interaction between the activist community and the establishment of scientists and regulators. I remember I gave a keynote address, and Peter Staley, who now 30 years later has become a very close personal friend of mine, gave a very stirring keynote address about the importance of paying attention to activists. And if you fast-forward 30 years, from that 1990 meeting till now, we have people who were activists at the time who are now actually full colleagues who are integrated into everything that we do, from the research agenda, to the conduct of clinical trials, to the interpretation of the data. So that has been an amazing evolution.

The other thing that is amazing in its evolution is the amount that we’ve learned about HIV pathogenesis, the reservoir, the potential for controlling the virus, either in the absence of antiretroviral [treatment] or in a modified regimen that takes away the need to have a single pill or multiple pills every single day. The thing that remains the holy grail of unaccomplished goals is the development of a highly effective, safe vaccine. And that is something that’s not surprising because of the very special situation with HIV, that the body—as much as we study pathogenesis and understand it so incredibly well—the body does not make an adequate immune response against HIV, which is the reason why no one has yet spontaneously cleared the virus by their immune system. And so what we need to do, and where we’re combination putting a lot of effort into, but also struggling with, is the issue of the development of a vaccine that would be effective enough to be able to be deployed.

We have one situation that took place, well after that meeting in San Francisco, where a trial of a candidate vaccine—in a trial named RV 144 that took place in Thailand—showed a 31% efficacy, which gave us some great hints of correlates of immunity and are the basis for a number of subsequent trials, but still was not good enough to deploy. So we have a number of very large vaccine trials, going on now throughout the world, including a heavy concentration in southern Africa. But we also are pursuing another line of vaccine research, which is the attempt to present to the body, in the proper conformation with sequential immunizations, the capability of making broadly neutralizing antibodies. And if we're successful in that, then I think we have a really good chance of developing a vaccine that would have an efficacy and safety profile good enough to actually deploy it.

We have a variety of very, very good preventive measures now that we did not have in 1990. Just think, that was 30 years ago and the prevention was mostly behavioral issues and condoms and things like that. Right now, [there’s] the preexposure prophylaxis, either with a pill that you take every day like Truvada, which is a combination of tenofovir and emtricitabine, or what we’re working on now [with] data that came out a week or 2 ago showing that an injectable form of a drug called cabotegravir, which, when given every couple of months, can actually prevent the acquisition of HIV in people at risk, as well as, or maybe even a little better, but certainly as well as Truvada can.

So, if you look at what's happened since that meeting, we have therapies now that can bring a person's viral load to below detectable in a sustained way. An offshoot of that is not only saving the lives of countless individuals, but the concept that was never spoken of back in 1990, what's part of our lexicon right now, is the issue of treatment as prevention, or “U equals U” [undetectable = untransmittable]. Namely, if you are undetectable and your viral load is beyond or beneath the level of detection by classical assays, that makes it essentially impossible to transmit the virus to another individual.

So if you look at all those things that we didn’t have when I was giving that plenary address in San Francisco and Peter Staley was giving his plenary address, and then-secretary of HHS Louis Sullivan was up there getting condoms thrown at him from the audience—that took place in 1992—we didn’t have therapy that was effective. We didn‘t have treatment as prevention and “U equals U.” We didn’t have exquisitely effective preexposure prophylaxis, and we didn’t have a vaccine. Of all of that, the things that we don’t have still are a vaccine and a cure. And we’re trying for a cure, but a cure is going to be problematic.

Cure means that you essentially eradicate the virus, which we have not been able to do, or suppress it in a way that doesn’t require daily antiretroviral drugs. So the 2 remaining challenges, if we were having the meeting now in San Francisco—and we’re going to be having it virtually—is where are we on the road to a cure? And where are we on the road to a vaccine?