A blood test for analysis of HIV.
Last week, top experts on HIV/AIDS convened in Amsterdam for the 22nd International AIDS conference, and the mood was not great. Even though remarkable advances in treating HIV have led to effective management for many people living with the disease, and its overall incidence has declined, there are signs that the virus could make a troubling comeback.
"In a perfect world, we'd get a vaccine like the HPV vaccine that was 100% effective and I think that's ultimately what we're going to strive for."
Growing resistance to current HIV drugs, a population boom in Sub-Saharan Africa, and insufficient public health resources are all poised to contribute to a second AIDS pandemic, according to published reports.
Already, the virus is nowhere near under control. Though the infection rate has declined 47 percent since its peak in 1996, last year 1.8 million people became newly infected with HIV around the world, and 37 million people are currently living with it. About 1 million people die of AIDS every year, making it the fourth biggest killer in low-income countries.
Leapsmag Editor-in-Chief Kira Peikoff reached out to Dr. Carl Dieffenbach, Director of the Division of AIDS at the National Institute of Allergy and Infectious Diseases, to find out what the U.S. government is doing to develop an HIV vaccine and cure. This interview has been edited and condensed for clarity.
What is the general trajectory of research in HIV/AIDS today?
We can break it down to two specific domains: focus on treatment and cure, and prevention.
Let's start with people living with HIV. This is the area where we've had the most success over the past 30 plus years, because we've taken a disease that was essentially a death sentence and converted it through the development of medications to a treatable chronic disease.
The second half of this equation is, can we cure or create a functional cure for people living with HIV? And the definition of functional cure would be the absence of circulating virus in the body in the absence of therapy. Essentially the human body would control the HIV infection within the individual. That is a much more, very early research stage of discovery. There are some interesting signals but it's still in need of innovation.
I'd like to make a contrast between what we are able to do with a virus called Hepatitis C and what we can do with the virus HIV. Hep C, with 12 weeks of highly active antiviral therapy, we can cure 95 to 100% of infections. With HIV, we cannot do that. The difference is the behavior of the virus. HIV integrates into the host's genome. Hep C is an RNA virus that stays in the cytoplasm of the cell and never gets into the DNA.
On the prevention side, we have two strategies: The first is pre-exposure prophylaxis. Then of course, we have the need for a safe, effective and durable HIV vaccine, which is a very active area of discovery. We've had some spectacular success with RV144, and we're following up on that success, and other vaccines are in the pipeline. Whether they are sufficient to provide the level of durability and activity is not yet clear, but progress has been made and there's still the need for innovation.
The most important breakthrough in the past 5 to 10 years has been the discovery of broad neutralizing monoclonal antibodies. They are proteins that the body makes, and not everybody who's HIV infected makes these antibodies, but we've been able to clone out these antibodies from certain individuals that are highly potent, and when used either singly or in combination, can truly neutralize the vast majority of HIV strains. Can those be used by themselves as treatment or as prevention? That is the question.
Can you explain more about RV144 and why you consider it a success?
Prior to RV144, we had run a number of vaccine studies and nothing had ever statistically shown to be protective. RV144 showed a level of efficacy of about 31 percent, which was statistically significant. Not enough to take forward into other studies, but it allowed us to generate some ideas about why this worked, go back to the drawing board, and redesign the immunogens to optimize and test the next generation for this vaccine. We just recently opened that new study, the follow-up to RV144, called HVTN702. That's up and enrolling and moving along quite nicely.
Carl Dieffenbach, Director of the Division of AIDS at the National Institute of Allergy and Infectious Diseases
(Courtesy)
Where is that enrolling?
Primarily in Sub-Saharan Africa and South Africa.
When will you expect to see signals from that?
Between 2020 and 2021. It's complicated because the signal also takes into account the durability. After a certain time of vaccination, we're going to count up endpoints.
How would you explain the main scientific obstacle in the way of creating a very efficacious HIV vaccine?
Simply put, it's the black box of the human immune system. HIV employs a shield technology, and the virus is constantly changing its shield to protect itself, but there are some key parts of the virus that it cannot shield, so that's the trick – to be able to target that.
So, you're trying to find the Achilles' Heel of the virus?
Exactly. To make a flu vaccine or a Zika vaccine or even an Ebola vaccine, the virus is a little bit more forthcoming with the target. In HIV, the virus does everything in its power to hide the target, so we're dealing with a well-adapted [adversary] that actively avoids neutralization. That's the scientific challenge we face.
What's next?
On the vaccine side, we are currently performing, in collaboration with partners, two vaccine trials – HVTN702, which we talked about, and another one called 705. If either of those are highly successful, they would both require an additional phase 3 clinical trial before they could be licensed. This is an important but not final step. Then we would move into scale up to global vaccination. Those conversations have begun but they are not very far along and need additional attention.
What percent of people in the current trials would need to be protected to move on to phase 3?
Between 50 and 60 percent. That comes with this question of durability: how long does the vaccine last?
It also includes, can we simplify the vaccine regimen? The vaccines we're testing right now are multiple shots over a period of time. Can we get more like the polio or smallpox vaccine, a shot with a booster down the road?
We're dealing with sovereign nations. We're doing this in partnership, not as helicopter-type researchers.
If these current trials pan out, do you think kids in the developed world will end up getting an HIV vaccine one day? Or just people in-at risk areas?
That's a good question. I don't have an answer to that. In a perfect world, we'd get a vaccine like the HPV vaccine that was 100% effective and I think that's ultimately what we're going to strive for. That's where that second or third generation of vaccines that trigger broad neutralizing antibodies come in.
With any luck at all, globally, the combination of antiretroviral treatment, pre-exposure prophylaxis and other prevention and treatment strategies will lower the incidence rate where the HIV pandemic continues to wane, and we will then be able to either target the vaccine or roll it out in a way that is both cost effective and destigmatizing.
And also, what does the country want? We're dealing with sovereign nations. We're doing this in partnership, not as helicopter-type researchers.
How close do you think we are globally to eradicating HIV infections?
Eradication's a big word. It means no new infections. We are nowhere close to eradicating HIV. Whether or not we can continue to bend the curve on the epidemic and have less infections so that the total number of people continues to decline over time, I think we can achieve that if we had the political will. And that's not just the U.S. political will. That's the will of the world. We have the tools, albeit they're not perfect. But that's where a vaccine that is efficacious and simple to deliver could be the gamechanger.
In 2015, human poop was valued at $9.5 billion per year, which today would be $11.5 billion. The Ocean Sewage Alliance is uniting experts from key sectors to change how we handle our sewage and, in the process, create all sorts of economic benefits.
Most of us don’t think much about what happens after we flush the toilet. Most of us probably assume that the substances we flush go “somewhere” and are dealt with safely. But we typically don’t think about it beyond that.
Most of us also probably don’t think about what’s in the ocean or lakes we swim in. Since others are swimming, jumping in is just fine. But our waterways are far from clean. In fact, at times they are incredibly filthy. In the US, we are dumping 1.2 trillion of gallons of untreated sewage into the environment every year. Just New York City alone discharges 27 billion gallons into the Hudson River basin annually.
How does this happen? Part of it is the unfortunate side effect of our sewage system design that dates back to over a century ago when cities were smaller and fewer people were living so close together.
Back then, engineers designed the so-called “combine sewer overflow systems,” or CSOs, in which the storm water pipes are connected to the sanitary sewer pipes. In normal conditions, the sewage effluent from homes flows to the treatment plants where it gets cleaned and released into the waterways. But when it rains, the pipe system becomes so overwhelmed with water that the treatment plant can’t process it fast enough. So the treatment plant has to release the excess water through its discharge pipes—directly, without treatment, into streams, rivers and the ocean.
The 1.2 trillion gallons of CSO releases isn’t even the full picture. There are also discharges from poorly maintained septic systems, cesspools and busted pipes of the aging wastewater infrastructure. The state of Hawaii alone has 88,000 cesspools that need replacing and are currently leaking 53 million gallons of raw sewage daily into their coastal waters. You may think twice about swimming on your Hawaii vacations.
Overall, the US is facing a $271 billion backlog in wastewater infrastructure projects to update these aging systems. Across the Western world, countries are facing similar challenges with their aging sewage systems, especially the UK and European Union.
That’s not to say that other parts of the planet are in better shape. Out of the 7+ billion people populating our earth, 4.2 billion don’t have access to safe sanitation. Included in this insane number are roughly 2 billion people who have no toilet at all. Whether washed by rains or dumped directly into the waterways, a lot of this sludge pollutes the environment, the drinking water, and ultimately the ocean.
Pipes pour water onto a rocky shore in Jakarta, Indonesia.
Tom Fisk
What complicates this from an ocean health perspective is that it’s not just poop and pee that gets dumped into nearby waterways. It is all the things we put in and on our bodies and flush down our drains. That vicious mix of chemicals includes caffeine, antibiotics, antidepressants, painkillers, hormones, microplastics, cocaine, cooking oils, paint thinners, and PFAS—the forever chemicals present in everything from breathable clothing to fire retardant fabrics of our living room couches. Recent reports have found all of the above substances in fish—and then some.
Why do we allow so much untreated sewage spill into the sea? Frankly speaking, for decades scientists and engineers thought that the ocean could handle it. The mantra back then was “dilution is the solution to pollution,” which might’ve worked when there were much fewer people living on earth—but not now. Today science is telling us that this old approach doesn’t hold. That marine habitats are much more sensitive than we had expected and can’t handle the amount of wastewater we are discharging into them.
The excess nitrogen and phosphorus that the sewage (and agricultural runoff) dumps into the water causes harmful algal blooms, more commonly known as red or brown tides. The water column is overtaken by tiny algae that sucks up all the oxygen from the water, creating dead zones like the big fish kills in the Gulf of Mexico. These algae also cause public health issues by releasing gases toxic to people and animals, including dementia, neurological damage, and respiratory illness. Marshes and mangroves end up with weakened root systems and start dying off. In a wastewater modeling study I published last year, we found that 31 percent of salt marshes globally were heavily polluted with human sewage. Coral reefs get riddled with disease and overgrown by seaweed.
We could convert sewage into high-value goods. It can be used to generate electricity, fertilizer, and drinking water. The technologies not only exist but are getting better and more efficient all the time.
Moreover, by way of our sewage, we managed to transmit a human pathogen—Serratia marcescens, which causes urinary, respiratory and other infections in people—to corals! Recent reports from the Florida Keys are showing white pox disease popping up in elk horn corals caused by S.marcescens, which somehow managed to jump species. Many recent studies have documented just how common this type of pollution is across the globe.
Yet, there is some good news in that abysmal sewage flow. Just like with plastic pollution, realizing that there’s a problem is the first step, so awareness is key. That’s exactly why I co-founded Ocean Sewage Alliance last year—a nonprofit that aims to “re-potty train the world” by breaking taboos in talking about the poop and pee problem, as well as uniting experts from various key sectors to work together to end sewage pollution in coastal areas.
To end this pollution, we have to change the ways we handle our sewage. Even more exciting is that by solving the sewage problem we can create all sorts of economic benefits. In 2015, human poop was valued at $9.5 billion a year globally, which today would be $11.5 billion per year.
What would one do with that sh$t?
We could convert it into high-value goods. Sewage can be used to generate electricity, fertilizer, and drinking water. The technologies not only exist but are getting better and more efficient all the time. Some exciting examples include biodigesters and urine diversion (or peecycling) systems that can produce fertilizer and biogas, essentially natural gas. The United Nations estimates that the biogas produced from poop could provide electricity for 138 million homes. And the recovered and cleaned water can be used for irrigation, laundry and flushing toilets. It can even be refined to the point that it is safe for drinking water – just ask the folks in Orange County, CA who have been doing so for the last few decades.
How do we deal with all the human-made pollutants in our sewage? There is technology for that too. Called pyrolysis, it heats up sludge to high temperatures in the absence of oxygen, which causes most of the substances to degrade and fall apart.
There are solutions to the problems—as long as we acknowledge that the problems exist. The fact that you are reading this means that you are part of the solution already. The next time you flush your toilet, think about where this output may flow. Does your septic system work properly? Does your local treatment plant discharge raw sewage on rainy days? Can that plant implement newer technologies that can upcycle waste? These questions are part of re-potty training the world, one household at a time. And together, these households are the force that can turn back the toxic sewage tide. And keep our oceans blue.
