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Medical News & Perspectives
July 11, 2018

Anthony Fauci, MD: Working to End HIV/AIDS

JAMA. Published online July 11, 2018. doi:10.1001/jama.2018.8216

In late spring of 1981, Anthony Fauci, MD, then a 40-year-old immunologist, was in his office at the National Institutes of Health (NIH) Clinical Center when a history-changing report came across his desk. The June 5 Morbidity and Mortality Weekly Report (MMWR) from what was then called the Centers for Disease Control documented Pneumocystis carinii pneumonia in 5 gay men presenting at 3 Los Angeles hospitals. Prior to this, the rare lung infection was almost exclusively limited to severely immunosuppressed patients, making these cases in previously healthy patients unusual.

Fauci thought it was a fluke. But a month later, in early July, another issue of MMWR came in, this time reporting that 26 gay men in Los Angeles, San Francisco, and New York were recently diagnosed with the uncommon and aggressive cancer Kaposi sarcoma and other opportunistic infections.

At that point, Fauci knew it was no fluke. It was the beginning of the AIDS epidemic, although the new disease didn’t have a name—or a known cause—yet.

“That turned out to be the real turning point in my career, if not my life,” Fauci says. He and his colleagues assumed that a sexually transmitted virus caused the disease. “But like everybody else, I didn’t have any idea what it was,” he says. As an internist trained in both infectious diseases and clinical immunology, he realized that he was in a unique position to make a real impact on a terrible illness.

Fauci’s research on the pathogenesis of HIV, which he juggled while tending to patients with AIDS, laid the framework for early treatments, and in 1984 he was named director of the National Institute of Allergy and Infectious Diseases at the NIH, a position he’s held for 34 years. In that role, he developed programs focused on the discovery of antiretroviral drugs and their testing in clinical trials networks. Several generations of antiretroviral therapies have since been developed, transforming HIV infection from a death sentence into a manageable chronic disease if treated.

Yet much more work needs to be done, Fauci says. More than a million people in the United States are living with HIV, with tens of thousands of new infections and more than 6000 deaths every year. Globally, 36.7 million people were living with the infection and 1.8 million people were newly infected in 2016. That year, 1 million people worldwide died from AIDS-related illnesses, bringing the total death toll to a staggering 35 million since the start of the pandemic.

Just weeks before the 22nd International AIDS Conference, Fauci spoke with JAMA about how far we’ve come in treating and preventing HIV/AIDS—and how much farther we need to go to reach his ultimate goal of eliminating the disease.

JAMA:Given how the landscape of HIV and AIDS has changed over the past 4 decades, has the pendulum of perception perhaps swung too far, where people may not be taking HIV as seriously?

Dr Fauci:There certainly is an element of that because we have been so successful, particularly in the arena of treatment. When I was taking care of HIV-infected individuals in the early and mid-1980s, before we had any therapy at all, the median survival was approximately a year. Which means that 50% of the patients would be dead in a year. Around 1996, we developed the triple combination therapies, which gave durable control of the viral load. The whole complexion changed, so the scare of HIV lessened somewhat. And with that came, in some quarters, this issue of complacency.

JAMA:Do you think that complacency has affected physicians?

Dr Fauci:I don’t think so. What I do see is a different attitude toward hope, so that when someone is infected—even someone who comes in with advanced disease—you don’t have that somewhat despairing feeling that there’s not much you can do about it. Right now it’s an uplifting feeling that you can really do something with the patient. That you [won’t] just stand there and watch your patient deteriorate.

JAMA:Are people getting tested enough?

Dr Fauci:The answer is no, [although] it’s certainly much more now than it was in the past. Today there are multiple reasons to test someone. You can put the person on therapy and save the life of that individual. The other reason [is] what we call “treatment as prevention.” We now know from very good studies that if you treat somebody with antiretroviral therapy and bring their viral level down to below detectable, it makes it virtually impossible for that person to transmit the virus to their sexual partner.

JAMA:How many new infections are we seeing annually these days in the United States? And which groups are most vulnerable?

Dr Fauci:There’s a painful answer to that question. We should be doing much, much better than we’re doing. Back in the day, at the peak of infection, we had 120 000 to 150 000 new infections per year. Right now it’s about 40 000 new infections per year. The problem with that number is that it has plateaued for the last 15 years. We’ve reached some sort of an artificial ceiling. The demography of HIV infection has changed dramatically over the last few decades. In the United States, 12% of the population is African American, yet almost half of the new infections are among African Americans, particularly African American men who have sex with men.

JAMA:What’s being done to help in this community?

Dr Fauci:We’re intensifying community outreach. Years ago there was this concern about stigmatizing people by directing your messages of prevention to any particular group. I think we’ve put that behind us right now. We have to be very aggressive in going out into the community and making [those who are at highest risk] aware of how they can protect themselves. If you’re in a risk population, get tested every 6 months to a year. Once you get tested, if you are uninfected and continuing to practice risk behavior, there are things called preexposure prophylaxis [PrEP]; there’s proper use of condoms.

JAMA:Why are people in the United States still dying from AIDS?

Dr Fauci:If we identified [everyone] who was HIV-infected in the country and put [them all] on antiretroviral therapy, it would essentially be the end of AIDS. But unfortunately that’s not the case. Up to 14% or 15% of individuals who are infected don’t even know they are infected.

And then there are those who are not in a health care system. Here at the NIH, it is not an unusual situation for us to admit someone who presents with a viral load over a million. And here we are in 2018. That should never happen, that you have someone with that far advanced disease who comes in for the first time presenting with an opportunistic infection. But it still does happen.

JAMA:The percentage of people in the United States taking PrEP who could benefit from it is abysmal. It’s around 10%, correct?

Dr Fauci:Correct. We’re trying to do something about it. It is estimated that about 1 million people in the United States are at high enough risk that they would greatly benefit from the use of PrEP. [It’s] a single pill once a day [called] Truvada. [But] only a small percentage of people know about it—not only the people who are at risk, but even the health care providers. About one-third of the community health care providers don’t appreciate the fact that PrEP can be available for people at high risk. So, we’ve got to do a much, much better job of advertising the benefits.

JAMA:What are some of the underlying reasons for US outbreaks of HIV in the past few years?

Dr Fauci:Certainly injection drug use, which is related to the opioid crisis, has been the source of the outbreaks that we’ve recently seen in the United States, [like] the well-known [case] in the state of Indiana, and now in a number of regions in the country. You go from oral opioids to [injecting opioids] and that’s how you get the increase in HIV infection.

JAMA:What do you think about needle exchanges?

Dr Fauci:They’re very, very important in preventing the injection-drug-use transmission of HIV. I was a part of a task force many years ago during the Clinton administration which examined all of the data to ask the question, “If you have needle exchange, does it decrease the risk of HIV infection and/or does it increase the illicit use of intravenous drugs of any kind?” And the answer is [that] it does not at all increase intravenous drug use and it definitely decreased the incidence of HIV infection. So I am 100% for the use of needle-exchange programs. I’ve been pushing for them for the last couple of decades. There’s always been [the] issue of the federal funding not being given, but the states have really taken over and there are major needle-exchange programs right now.

JAMA:Let’s turn to people who have been in treatment for HIV for a long time. What are we seeing clinically today with these patients?

Dr Fauci:As we have more experience with people who have been infected for a long time, there are a number of comorbidities that we’re recognizing. People who are HIV-infected have twice the incidence of cardiovascular events as those who are not infected. And if you’re a woman you have 3 times the incidence of a cardiovascular event if you’re HIV-infected. That is all related to the degree of immune activation and inflammation, which still remains even when you are on adequate antiretroviral therapy. A subliminal amount of immune activation leads to increases in things like heart disease, stroke, kidney disease, liver disease, and premature aging. When you look at their tissues, physiologically it looks like they are older than they really are. Part of our program here at NIH is now to make sure we’re aware of and diagnose these comorbidities, as well as prevent them.

JAMA:Drug resistance has been a huge part of the antiretroviral therapy story. Are we still dealing with it?

Dr Fauci:We will always be dealing with drug resistance. In order [for HIV] to mutate to get resistance you have to replicate [the virus]. If everybody had complete suppression of the virus there would be no antiviral resistance. But that’s not the case. We need to try and avoid it by making sure we get people’s viral load to below [a] detectable level and we need to get a better pipeline of drugs that can substitute for the drugs to which the virus has developed resistance.

JAMA:One of the things you’re working to develop is long-acting therapies. Why is that important?

Dr Fauci:There’s a certain percentage of people who get what’s called drug fatigue. They psychologically and otherwise do not like the idea of having to take a pill every single day. Either because they don’t want to be reminded that they have an infection or [because they] get side effects or adverse events from the drugs. There are a number of drugs, such as cabotegravir, that can be administered over intervals, and we’re trying to stretch out the intervals. Right now a study is looking at giving it every 8 weeks or every 2 months. It is almost certain that we can even do better than that, where you can probably give an injection every 6 months and still get the effect of giving a drug every day.

JAMA:You’re passionate about the need for a prophylactic vaccine. Tell us why.

Dr Fauci:If you really want to turn off a viral infection [pandemic] the answer has to have a vaccine as part of the process. Given all the other nonvaccine prevention modalities, I believe that if we have a vaccine that’s 50%, 55%, maybe at the best 60%, effective and combine that with nonvaccine prevention modalities, we could really turn off this pandemic and put an end to it as we know it.

JAMA:There are also people working on a cure. Do you think it’s possible to cure HIV?

Dr Fauci:I think it’s much more likely that we will have a way of getting people off classical antiretroviral therapy and sustain them in a remission where the virus doesn’t rebound.

JAMA:There’s been a lot of research and discovery around viral reservoirs. What are they and why are they important?

Dr Fauci:Viral reservoirs are the critical stumbling block to a cure for HIV. Very soon after the virus enters your body, you develop what’s called a reservoir of virus—latently infected cells that just sit there. It never goes away, even with antiretroviral therapy. It’s a natural, very perplexing part of the pathogenesis of HIV.

JAMA:What’s the most important progress we’ve made this decade in the HIV epidemic?

Dr Fauci:Treatment as prevention and preexposure prophylaxis, because if we really implement them properly, theoretically you could shut the epidemic off.

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