Free Your (and Carl's) Mind: An Open Letter to Anthony Fauci About HIV Prevention Research Priorities
Dear Anthony S. Fauci, M.D., Director of the National Institute of Allergy and Infectious Diseases,
I turned 18 in 1984, the same year I kicked my closet door down. Missing the "first wave of HIV," I ended up testing positive 11 very sexually active years later, in 1995. While I escaped the virus directly in those early years, I like many others witnessed extraordinary horror and pain and, like many, lost friends, lovers, acquaintances, serenity, peace of mind, hope. So much loss.
That second wave, though, got me. In fact, love got me. I was in love, and when we stopped using condoms, neither of us discussed it. I was in love when HIV came knocking.
I have immense gratitude for the many heroes of ACT UP who got right up in your face back in the late '80s. And that gratitude extends to you personally. Kudos to you for reaching out to those amazing activists who were calling you an "incompetent idiot," a "monster" and a "murderer" -- for what they justifiably felt was a terribly sluggish (at best hateful and at worst homophobic and racist) response to an epidemic that was wiping out whole communities -- my community -- and promising to listen and do better.
You listened and you did better. You listened and you led. So, when I tested positive, I soon had a number of treatment options, and I continue to have treatment options 22 years later -- options that have improved over and over and over again. Hey, I am alive 22 years later -- something I did not expect. None of us did.
It was that second wave that propelled me into the work I am doing now, passionately and persistently advocating for new HIV prevention technologies beyond condoms -- whatever the flavor -- for the last 12 years at the helm of a plucky international network of researchers, policymakers, funders and advocates I cofounded called IRMA (International Rectal Microbicide Advocates), a project of the AIDS Foundation of Chicago.
In the last several years since U.S. Food and Drug Administration approval of tenofovir/emtricitabine (Truvada) for pre-exposure prophylaxis (PrEP), I have also worked to help implement this wonderful intervention on the ground, in addition to continuing to call for a "toolbox" of interventions, for a buffet of options similar to the offerings available for contraception.
So, let me cut to the chase, Tony.
As you know, your colleague Carl W. Dieffenbach, Ph.D., director of the Division of AIDS, National Institute of Allergy and Infectious Diseases, National Institutes of Health, is leading the current, ongoing NIH effort to "refine the HIV research enterprise" and prioritize the 2021-2027 scientific agenda around new HIV prevention technologies.
I know Carl; I've sat down with him and have enjoyed great conversations with him. I am fond of Carl for many reasons; I think he is smart, and I know he cares deeply about his work and ending the epidemic. We see eye to eye on a number of things.
But I am not on board with his vision for the future of HIV prevention research.
I hope you will listen. I am not going to call you a monster or a murderer, but I hope you will listen like you did decades ago. Not that I don't have it in me, just to be clear.
Diffenbach's Vision: Not Enough Trees in a Rebounding Forest
On AVAC's Sept. 5 global webinar devoted to this topic Carl, noting that "we stand on the shoulders of past successes" laid out his evolving ideas once again for folks in the field. He spoke about the need to develop products that "elicit in people the desire to use the products" because "[w]e can't have situations where people feel stigmatized by the prevention strategies we are offering them."
He expressed the desire to be innovative and "push the envelope" and noted that "new tools need to be safe, acceptable, desired, highly effective and protect systemically." He stressed how we must define the needs of vulnerable populations and tailor-fit prevention strategies to them, frequently highlighting the imperative of focusing on adolescents and young people.
"We don't want to get into a one-size-fits-all situation," Carl told the global webinar audience. "What may work for an adolescent or a young woman in the area around Durban, South Africa, may be completely different than [for] a young black gay man in rural Georgia."
He likened the HIV epidemic to a fire that burnt an entire forest down. Through research and implementation activities, "we have brought the forest back with lots of new growth," he said. It's a nice metaphor, but in his vision for the future of HIV prevention, he is neglecting some important stands of trees in that rebounding forest. His laser focus on HIV prevention products that are long acting and systemic, durable for six months or longer (all of which are good things), misses out on the need for products that are short acting, localized, user controlled and free of long-term commitment -- namely microbicides.
While he correctly points out that one size will not fit all and how we must have tailored approaches, he essentially throws cold water on that notion by also saying we need to "talk first and foremost about reality" and "reality-based" strategies for effective prevention and that "we need to be careful about what people want." He rhetorically asks whether it is pharmacologically possible to give people what they want and says it simply may not be, saying that "everybody would like something simple and easy -- that would give a tremendous amount of pleasure and satisfaction -- and it just may not be possible."
His pessimism is focused on microbicides, saving all his optimism for a narrow belief that the long acting and systemic is the answer in a very "silver bullet" sort of way. While the microbicide field has produced a vaginal ring that works when you use it, providing protection to women who otherwise would likely have none, he seems to believe that is as far as we can go, that we are done with that: time to move on.
I think he is wrong.
The Case for Options Beyond Long-Acting HIV Prevention
Not everyone wants systemic drug exposure. Not everyone wants long-acting prevention -- especially if their sex life is less frequent or more sporadic. Not everyone wants to go to the clinic every two months for an injection -- as folks need to do with the cabotegravir injectable currently being studied in large-scale efficacy trials (one has started; another is poised to start). Every two months means six trips to the clinic every year for an individual to get his or her HIV prevention shots. What a huge commitment. The notion that this product will somehow "fix" the adherence issues we are seeing with daily tablet taking (per the PrEP dosing protocol) is misguided.
To that point, take a look at this paper, "Hormonal Contraceptive Discontinuation Patterns According to Formulation: Investigation of Associations in an Administrative Claims Database," which found that women were most likely to discontinue injectable contraception and most likely to stick with oral contraception.
Different strokes for different folks.
Doing PrEP outreach work, we are seeing plenty of folks who don't like taking a daily pill, that's for sure. For some of them, a long-acting injectable or implant might be perfect. But others are going to want to use a product that doesn't require that commitment, that doesn't require a visit to a clinic to have it administered. Some people hate shots or freak out at something being implanted in them. Carl talks about tailoring and creating products that people want to use -- but he seems to be quick to ignore the people who don't fit his vision. These folks will want things they can use when they have sex -- and not to use them when they don't have sex. Pretty simple conceptually -- and pretty sad to just throw this whole concept into the trash.
From 2000 to 2016, over $3 billion was spent on microbicide research, and over four times that amount (more than $12 billion) was spent on developing a vaccine during the same period. We don't have a vaccine yet, do we? And no one says we should stop the effort because we haven't figured it out yet. I certainly don't. On the other hand, we have a vaginal ring moving towards licensure -- and I have watched on multiple occasions as this gets treated derisively by Carl, who also appears unfazed by tossing away our investments in rectal microbicide research.
It's Not Just About the Ring
Yes, we need to work on that vaginal microbicide ring to improve it in a number of ways -- just like we have improved treatment over the years, iterating from handfuls of very toxic pills with super complicated dosing to once-daily pills with little-to-no side effects.
We need to work on that ring to offer contraception alongside the HIV prevention, and ideally, prevention against other sexually transmitted infections, as well.
The vaginal ring for HIV prevention is just the beginning.
We also need other modalities, and hello, we need products that work rectally for humans who have anal sex. There are really interesting things happening in the rectal pipeline -- interesting modes of delivery, including behaviorally congruent rectal douches. And there are new drugs such as Griffithsin, which shows high activity against HIV but is a natural product, not a typical antiretroviral drug.
Are the millions spent, and being spent, on rectal microbicide development simply going to fund some fancy talks at international AIDS conferences and lovely papers in prestigious journals with zero hope of making a difference in the lives real people? With zero chance of becoming a product we can use? What about the lives of the people who have been showing up for these studies and volunteering their time and their bodies, what about the lives of people who say they want microbicide options? To them we say, "Sorry, just face reality, you can't always have what you want?"
"But thank you for time, anyhow?"
That is unacceptable.
Something else about me. I'm a taxpayer. I engage with my elected officials. I hail from Illinois, the state that led the way on the Microbicide Development Act. You may remember a young United States senator named Barack Obama who sponsored the legislation. My rep in the House, Jan Schakowsky, also sponsored it.
It never passed, but everything in the legislation was enacted nonetheless. Funny how things work. I am not going to sit back and watch it all disappear without a fight.
"Let's free our minds to consider alternative innovation strategies," Carl told us on that webinar.
Please Tony, help Carl free his mind to consider microbicides with the same passion and intensity and commitment he has for vaccines and long-acting formulations. He has heard us say these things many times over this year, but he has yet to really listen, I am sorry to say. He seems to listen only when it fits in with his vision.
Can you help draw his attention to this missing stand of trees in the forest? They deserve a sustained, adequately funded chance to flourish.
And while I am asking for favors, could you also help ensure that the process of gathering input and feedback is transparent? Currently, no one has any idea what comments have come in or how Carl is responding to them. We deserve to see these exchanges and not to have them summarized for us.
Jim Pickett is the senior director of prevention advocacy and gay men's health at AIDS Foundation of Chicago and the chair of International Rectal Microbicide Advocates.