Challenges and Similarities in HIV, COVID-19 Crises: A Q&A With Anthony Fauci, MD

Am J Manag Care. 2020;26(7):282-283. https://doi.org/10.37765/ajmc.2020.43637

AJMC^®: It’s the journal’s 25th anniversary year, which coincides with the 30-year anniversary of your speech at the 6th International AIDS Society (IAS) Conference in 1990. At that time, you outlined the priority research gaps for the 1990s, and we were wondering, if you look ahead, where are the remaining gaps? Also, what are you most excited about in terms of HIV and AIDS research and, obviously, other types of virus research?

Anthony 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, 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 so what we need to do—and where we’re putting a lot of effort but also struggling with—is develop a vaccine that would be effective enough to be able to be deployed.

Right now, [we have] pre-exposure 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…showing that in 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 [than], but certainly as well as Truvada can.

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, as in “U equals U” [undetectable = untransmittable]. We didn’t have exquisitely effective pre-exposure prophylaxis, and we didn’t have a vaccine. Of all of that, the things we still don’t have 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—are where are we on the road to a cure? And where are we on the road to a vaccine?

AJMC^®: And where are we in terms of what you think the similarities are between HIV and coronavirus disease 2019 (COVID-19)? You talked about prevention, you talked about a cure, you talked about vaccines.

Fauci: Well, the common denominator is that they both started off as a new virus that the human species had never had any experience with. It jumped, as many of these new emerging infections do, from an animal reservoir to a human. The differences are profound. [One] difference is that [COVID-19] is highly efficiently transmitted from person to person by the respiratory route, which makes it very difficult to prevent yourself from getting infected except by doing draconian things that we’ve done with COVID-19; namely, [you] essentially shut down your country, lock it down, have such physical separation that you don’t transmit because you’re not physically close enough to transmit a respiratory infection. That is a very, very profound and draconian way of blocking infection.

HIV—although its impact is enormous, with over 80 million infections and over 37 million deaths and still over a million people getting infected each year—is so different because it’s insidious. It started off slow. When it started off, we saw the tip of the iceberg, not realizing that many more people were infected than we were actually seeing getting sick. So if you can get infected today, you could go 10 years before you actually get symptoms enough to make you feel sick. That’s very different from COVID-19. You get sick, it’s explosive, you get infected. You either get better within a period of a couple of weeks or you progress to disease and die. So they have so many things that are different about them but yet some things that are common denominators.

AJMC^®: In a recent article in the Journal of the International AIDS Society, you and your coauthor wrote, “We emphatically state that finding safe, effective, and durable vaccines for HIV and COVID-19 are NIAID’s top priorities. The world must have both.”¹ What are the current challenges in doing so?

Fauci: Well, I think the challenge for getting a vaccine against SARS-CoV-2 [severe acute respiratory syndrome coronavirus 2] is more of a time element. We feel fairly confident, given the fact that the body makes a pretty good immune response against natural infection, that you can get a vaccine to induce a similar response that could protect—you never guarantee that; there’s never a guarantee with vaccinology. But we feel fairly confident that we’ll get a vaccine. We’d like to get one.

And the projections are that it’s at least aspirationally possible by the end of the year and the beginning of 2021. Whereas with HIV, we’ve been working on a vaccine for 30-plus years. It is very difficult to get a vaccine because it’s very difficult to induce the body to do something that even natural infection doesn’t successfully allow it to do, [which] is to develop an adequate immune response to clear the virus. So the challenges are very, very different. I’m more confident that we’ll get a vaccine for SARS-CoV-2 than I am that we’ll get one against HIV, although I have cautious optimism that we’ll get it for both. But I think it’s going to be much easier to get it against the coronavirus.

AJMC^®: AstraZeneca said recently they expect to have or deliver a billion doses by the end of this year or early next year. Do you think that’s optimistic?

Fauci: No, I think they said ultimately a billion doses. I don’t think they’re going to have a billion doses by the end of this year, not a chance. They may have 100, 200 million doses, but it’s going to take a little while to get a billion doses.

AJMC^®: And also recently, as you know, 2 journals, the Lancet² and the New England Journal of Medicine,³ published retractions of 2 studies looking at hydroxychloroquine and chloroquine and cardiovascular disease in hospitalized patients. Do the circumstances around those studies alarm you in any way?

Fauci: Well, there was a particular data collecting company that was at the source and the root of the problem of having to retract those studies, because it could not validate or verify the data. When asked to see the data, the company said it wouldn’t make them available. So if there are questions about the integrity of the data, and you can’t validate them, that was the reason they were retracted. I mean, it just does nothing but cloud the picture. There are still ongoing, now, randomized controlled trials that ultimately will give us the answer about those drugs. So I think we just need to be patient and wait to see. The data from [the retracted studies] were based on a data collecting system that had people concerned and troubled.

AJMC^®: Is there anything you would recommend in terms of what’s happening now, to where we have rapidly publishing scientific and clinical research that would both keep the speed of publicly sharing developments while ensuring the accuracy even if it’s not full peer review?

Fauci: No, I think you said it yourself just now—you have to get a delicate balance between the public’s need to know data that could influence policy or public health approaches, without delaying the availability of those data, balanced against the need to get the proper peer review and to get it done in an expeditious manner. There’s good news and bad news. Some of the things that have come out were data that were important that came out much sooner than waiting for the process of peer review. However, a number of them are in the realm of “not verified yet,” so you’ve got to be careful you don’t propagate false information. I must say one thing that does encourage me is that the ability to get a peer-reviewed paper peer reviewed and out quickly is infinitely better and quicker than it was a few years ago. So the journals, I think, are stepping to the plate and forcing review, so as not to let a paper sit on their desk for 6 to 8 weeks, the way it used to be. I remember very clearly, the median time to get a review back would be like 8 weeks, which is ridiculous. Now when I get asked by a journal, particularly some of the top-line journals, to review a paper, part of the request is, “Can you have this [done] within 24 to 72 hours?” Like whoa! Whereas back then, it was, “Yes, please have it in 8 weeks.” So I think the journals’ capability of reviewing in an effective way, but doing it in a matter of days, as opposed to a matter of several weeks, is going to lessen the potential negative impact of getting un–peer-reviewed papers out there that overwhelm the papers that are peer reviewed. I think that we’re going to see a tendency toward peer-reviewed papers coming out much more quickly.

AJMC^®: Returning to COVID-19: It seems to be associated with a range of symptoms. Some people who get it, for instance, have reports of blood clots and neurological symptoms, and then a minority of children are coming down with that autoimmune COVID-19–related syndrome. Do you think this will always remain a respiratory disease or do you think it might someday become a systemic disease for some people?

Fauci: I think it already is a systemic disease for some people—we’re just not recognizing the full implications of the pathogenesis and the clinical manifestations. I don’t think it necessarily is going to evolve to do more systemically, but I think what we’ll likely see are more surprises like the multisystem inflammatory disease in children, MIS-C. I think we likely will see, as time goes by, some postinfection sequelae that we’ll only realize as we do good follow-up in natural history studies. The scope of the seriousness of this infection is extraordinary—from people who get a stuffy nose and a little sore throat and ache and they get better, to people who spend 14 days with a sustained fever and come out wiped out with a postviral dystonia, to people who have serious lung involvement that either puts them in the hospital or creates intubation needs, to people who die. I mean, that range of severity is really, in many respects, unprecedented. So I think we still have a lot to learn about the disease of COVID-19.

AJMC^®: You mentioned the activists and the period of time in 1990 that revolutionized the relationship between patients and doctors. And you’ve talked about your close friend, Larry Kramer, who passed away recently. Larry died right as the protests began across the country over the police killing of George Floyd. I’ve noticed that many of the commentators and observers and writers who are talking about this are noting the many health disparities that affect the black community. Do you think that we’re at an inflection point right now where the health and public health concerns of people of color will become heard more clearly?

Fauci: Well, I certainly hope so. Because what COVID-19 is doing is shedding another bright light on a systemic problem that has been with us for a very long period of time. In fact, even a little bit of a double whammy for the minority communities, particularly the African Americans, is that they have a higher incidence and prevalence of the comorbidities that make it more likely that you will have a complicated course of infection, leading to a serious disease, possibly hospitalization and even death, so the relative proportion of these comorbidities in people of color is significantly greater than of the population in general. The other thing is that the social determinants of health put people of color in a position—because of employment, socioeconomic status, availability of jobs—that makes it more likely for them to be in contact with an infected person and not able to physically separate themselves. So they have a greater risk (a) of getting infected and (b) of winding up, once they are infected, with a complication that is above and beyond the rate of complications of others. So this is another assault, as it were, on people of color, because if you look at other diseases—like HIV in the United States, [since] we’re talking today about the 30th anniversary of the [1990] IAS conference—if you look at HIV in this country, 13% of the population is African American, and yet up to 50% of the new infections [in men] are among African Americans, and about 60% [in women]. So here again, a greater burden of disease is being seen in the people who are minority groups, particularly people of color.

AJMC^®: When do you think we’ll know how durable the vaccines are once they come out?

Fauci: I think you have to follow it for a few years. That’s what we do with postvaccination studies. The first thing is, does it induce a response that’s protective? That’s the big hurdle. Once you show it’s protective, by follow-up studies, you can determine if the protection is 6 months, a year, 2 years, 5 years. I hope it’s measured in several years. But we don’t know that now.

AJMC^®: And lastly, you’ve always described yourself as a physician, scientist, and public health person, and you’ve put equal weight on the public health aspect. What can health care leaders do to keep emphasizing the importance of public health and restore the public trust in science? I’m thinking of the measles outbreaks a few years ago.

Fauci: Yeah, that’s a tough one. There is indeed a certain element of antiscience sentiment, not only in our own society in the United States, but [also] globally. My colleagues in Europe, I think, are having a worse time with that than we’re having here in the United States, and the situation in the United States is troubling. The point in the example that you gave—about the sort of skepticism about vaccine safety and the conspiracy theories that vaccines are being used to hurt people, as opposed to help them—is really quite troubling. A lot of it relates to a fundamental antiscience feeling because of moments of pushback from authority, and science tends to fall into the category of authoritative. People don’t like that. They don’t like people telling them what to do. But sometimes you go to the extreme and you don’t listen to things that you should be doing, because you think people are telling you that you have to do that. That’s a problem. But a lot of the vaccine stuff is misinformation, you know, dating back to the now-infamous fraudulent reporting of certain negative consequences of measles vaccines with autism and things like that. That really set us back. Because...particularly in the era of social media and the era of the internet, when something that’s incorrect gets propagated, it becomes very difficult to erase it, because it’s out there. This is not the way it used to be preinternet, pre–social media, when if something was false, you corrected and that was it. Not so now: Even if you correct it, it’s still lingering in there somewhere. That’s one of the problems.

REFERENCES

1. Dieffenbach CW, Fauci AS. The search for an HIV vaccine, the journey continues. J Int AIDS Soc. 2020;23(5):e25506. doi:10.1002/jia2.25506

2. Mehra MR, Ruschitzka F, Patel AN. Retraction—hydroxychloroquine or chloroquine with or without a macrolide for treatment of COVID-19: a multinational registry analysis. Lancet. 2020;395(10240):1820. doi:10.1016/S0140-6736(20)31324-6

3. Mehra MR, Desai SS, Kuy S, et al. Retraction: cardiovascular disease, drug therapy, and mortality in Covid-19. N Engl J Med. DOI: 10.1056/NEJMoa2007621. N Engl J Med. Published online June 4, 2020. doi:10.1056/NEJMc2021225

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