- My social media feed, my email inbox, every headline I see, seems to be about infectious disease treatments and vaccines.

We've got a COVID-19 vaccine in record-breaking time.

So how is it that we've gone 40 years without doing the same for HIV?

- When I was growing up, and even in my early days as a nurse, that was the big one.

It doesn't make headlines like it did back then, but HIV is still one of the biggest killers in the world.

- But some good news.

Cases have been on the decline since the 1980s.

And the United States and the World Health Organization are feeling pretty confident, and they've set an ambitious goal of ending HIV as a major threat by 2030.

- In the US, the official target is a 90% reduction in new cases by the year 2030.

- And all of this has been made possible without a vaccine.

How did that happen?

And why is getting a vaccine for HIV such a tough puzzle?

(upbeat jingle plays and whooshes) - Okay, so to answer why HIV cases are going down, the big reason is that even without a vaccine, we have incredibly effective methods to prevent infection.

We've got condoms.

We've got abstinence.

We've got teaching people not to share needles.

And we've also got biomedical interventions like medication.

We'll explain more in a minute, but first, let's look at why creating an HIV vaccine has been such an uphill struggle.

- Yeah, back in 1984, the government said we'd have a vaccine in two years.

Oops.

- 40 years later, there have been more than 200 potential vaccines studied, but only a handful of large-scale trials, and nothing that's come even close to the effectiveness that would get it approved for widespread use.

- For example, just last year, a clinical trial in sub-Saharan Africa was stopped early, because early results showed that the vaccine was only 25% effective.

It was unethical to continue.

Why is it so hard?

- The problem with HIV.

Two big problems.

Problem number one is it changes its genetic sequence very, very rapidly.

- So rapidly, in fact, one study found that HIV mutates more than any other living entity on the planet.

- It mutates thousands of times faster than COVID.

There are so many different variants of the same virus, so there can be more HIV variants in that single individual than flu strains across the globe in any single year.

- Traditional vaccines power up the body's natural defense system, and help it produce more antibodies.

A specific antibody targets a specific protein on the virus and tags it for destruction.

This is the approach that eliminated smallpox, and came close to eliminating polio and a whole string of childhood diseases.

- There's two lines of defenses that vaccines are meant to induce.

First the antibody, which is meant to keep the virus out.

It stops, it blocks the infectivity of the virus.

And then the T-cell immunity, which reduces the symptoms of the disease.

That stops the virus from replicating after it's gained entry into the body.

- But with HIV, that incredible mutation rate makes this much, much harder.

- And the problem is that our immune systems have evolved to recognize the enemy, to recognize the enemy from the clothes it's wearing.

If it's an enemy combatant, it would be wearing a different uniform.

And so it can be recognized as foreign.

So if the virus is continually changing its coat, it's changing its uniform, then the immune system is fooled.

The immune system can't recognize it as being an enemy combatant.

- In the first two decades of the HIV pandemic, these mutations were also a major hurdle to finding a treatment.

- Those mutations will allow the virus to become resistant to antiviral medications.

They will allow the virus to become resistant to the antibodies that vaccines are supposed to induce.

They allow the virus to become resistant to the T-cell immunity that our immune system is using to fight the virus.

This is the crux of what makes HIV such a formidable challenge to the scientific community in terms of not just vaccinating against it, but treating it and eradicating it.

- The first drugs to treat HIV, like AZT, lost effectiveness in a matter of months, because the virus mutated and developed resistance.

- But since the mid-1990s, doctors have understood that getting multiple medications at once was more effective.

This is called combination therapy.

And in 1996, the FDA approved a three-drug combination.

And this changed everything.

- I sort of watched, at San Francisco General, the beginning of the year, 40% of our patients in the inpatient setting at this hospital be living with AIDS, really sick, really didn't have those antiretroviral therapies.

And then I just watched over the second half of my residency, people rise from the dead.

It was literally a Lazarus effect, to watch it, to watch these antiretroviral therapies come out.

- Against three medications at once, the virus doesn't mutate fast enough to develop resistance.

And in fact, within months of triple-drug therapy, HIV death rates begin to plummet.

And since then, specific combinations have changed.

Side effects have gone down.

And this is essentially the treatment approach that doctors use today.

- And here's where this connects to the search for a vaccine.

Back in the very early 2000s, researchers decided to look at whether combination therapy could not just treat HIV infection, but also prevent it.

And turns out, it can.

In fact, it is highly effective as long as a person takes their medications.

- There are two distinct groups of people who take this medication.

People who are HIV positive, and people who are HIV negative but at high risk of infection.

And for people who are HIV positive, these antivirals are essentially 100 percent effective if they take them consistently.

In fact, some scientists call this U = U, for "Undetectable Equals Untransmissible."

In other words, if the level of virus in your blood is undetectable, you virtually cannot transmit it.

You can't pass it on to somebody else.

For the second group we mentioned, HIV negative but high risk, the drugs we mentioned are called pre-exposure prophylaxis, or PrEP, and they work remarkably well.

In fact, according to the CDC, PrEP, when used properly, can reduce the risk of infection from having sex by 99%.

99 percent!

- Now it is worth noting, there are fewer studies testing the effectiveness of PrEP in people who share needles.

The proven effectiveness is also less, and the CDC does not recommend relying on PrEP to prevent transmission through needle use.

- But still, this is a huge deal.

Even without a vaccine, we have a nearly foolproof way of blocking HIV transmission.

- But here's the catch.

Not enough people are taking it.

Across the United States, just one in four people who would actually benefit from PrEP, have a prescription.

And in many parts of the US, not to mention the world, it's even lower.

- Dr. Latesha Elopre, and Tommy Williams, a community health worker, work at a health clinic in Birmingham, Alabama.

- I believe one of the many reasons that the kids aren't accessing PrEP is because either they don't, believe it or not, know about it, and if they know about it, they don't really understand it, or they are not accurately identifying their level of risk.

- There's still a lot of stigma related to HIV.

And I think that's also a huge barrier, why people don't always access our preventative services like PrEP, or come in to get tested, because they're so fearful of that diagnosis and what it means for them when they reenter society.

- Another huge issue is cost.

Out of pocket, PrEP costs $2,000 a month.

There are federal programs that will help pay, but to get that help, you have to know a doctor, be willing to see them, and tell them that you're at high risk for HIV.

That's gotta be hard.

Alok, what say you?

- I mean, I heard so many barriers right now, Sheena.

It's like, yeah, PrEP works, we know it's an effective way of blocking transmission in people who are high risk, but you said it right there, you gotta be able to get to a doctor or a clinic, with a lot of people who don't have access for whatever reason.

Then there has to be that trusting relationship, which, you have to be open enough to this healthcare provider to say, like, "Hey, I'm high risk because of this particular situation."

And that's something that requires effort on both ends.

- You know, I'm really trying to understand how we can help this population a little bit better.

- For sure.

'Cause I think when we talk about building trust with healthcare professionals, part of that, from what I've experienced, is like continuity, is like seeing the same doctor, having someone that, you're like, this person has my best interests, they're not here to judge me, or anything like that.

So I can actually feel comfortable telling them, 'cause it must be hard to walk into an urgent care and be like, "Oh, I don't know you at all, but I'm gonna tell you about all the unprotected sex I've had, and my current situation, why I need PrEP."

Like that's not easy for everyone.

- It's just so many barriers to why we can't use this as a prevention, just yet.

- I mean, we can barely talk about unprotected sex and STDs in every part of this country, right?

Like, things are still so stigmatized about having conversations about HIV, or people who are high risk, or people who might be sex workers, or have multiple partners.

Like, there's all this judgy atmosphere.

So until we get past that, it's hard to make a conserved national message about this.

- It's super judgy.

And as a healthcare professional, just like you, we know that these diseases are way more common than people think.

They're way more common.

So when we talk about diseases like herpes, HIV, all the different STDs that are out there, there has to be a stigma taken off of it, so that people can have the proper self-awareness so that we can prevent these diseases from being as widespread as they are.

- Hear, hear.

Now, Dr. Stevenson, what would you say to someone if they were to say, "Hey, like we're putting so much money into vaccines, and maybe we should be putting money into prevention tools and to the treatments we already have, because they seem to be working better."

What would you say to that?

- Well, personally, I'm very enamored with that idea, because if we had a vaccine that gave us anything like the level of protection provided by pre-exposure prophylaxis, I mean, 98% plus protective against HIV infection.

If we had a vaccine that came anywhere close to that, we'd be saying, "Game over, we've done it.

Success."

- But the search for an HIV vaccine hasn't ended.

In fact, there is a clinical trial called Mosaico that's supposed to run for another two years.

And just this year, Moderna launched a pair of small trials using an mRNA vaccine to stimulate the body's immune system.

As you probably have heard, two of the most popular COVID-19 vaccines, one from Pfizer, one from Moderna, use a very similar technology.

- Which is to administer to the body HIV in a form that might elicit a desirable immune response.

And by desirable immune response, what they're looking for, are a specific class of antibody called a broadly neutralizing antibody.

- But real quick, what exactly is a broadly neutralizing antibody?

- So when someone becomes infected, the first thing your immune system does is it makes antibody to try and fight against the virus.

Now in an infected individual, those antibodies, they're not very potent, and they don't recognize a lot of enemy combatants.

They might recognize 30% of the enemy combatants out there, based on their uniform.

The broadly neutralizing antibodies recognize over 95, 98% of the foreign combatants.

They can neutralize many, many different strains of virus out there.

And that is what you want in a vaccine.

A vaccine that's gonna recognize all the different strains out there, and neutralize all those different virus strains that the individual could become exposed to.

- In fact, over the last decade, researchers have isolated more than 200 different antibodies that might be helpful.

They can be used as treatments, directly infusing them into a patient, but doctors have run into the same problem as with other medications.

Unless you find the right combination, the virus develops resistance.

- This treatment also would require repeat infusions every few weeks, or at most, months.

And it's expensive.

So for now at least, it's not a viable plan.

- But could the new vaccines help the body to make its own broadly neutralizing antibodies?

Well, that's what we're hoping for.

In the meantime, we have to rely on PrEP.

But that option is actually getting even better.

Instead of a daily pill, there are versions in clinical trials that only require an injection every month or two months.

- And fairly soon we could see treatments that provide protection for really long amounts of time.

You won't even have to think about it.

Kind of like a vaccine.

- We're gonna see long-acting formulations.

So that's going to translate into one pill a month, an infusion every year, and you're protected from HIV infection because of that.

I would say that's a lot of cause for celebration.

- And check out our bio for more information.

(upbeat jingle plays and whooshes) One thing before we take off.

As you all probably know, mental health has been a really important focus of this show.

With that, we wanna tell you about a new digital series from PBS called "Facing Suicide."

It shares really important stories about the roles friends and family play before and after mental health crises.

- You'll hear from suicide attempt survivors as they share their journeys and explore the healing found by opening up with a group of peers.

To watch, check out the link in our description, and we hope it can offer some inspiration to you, or someone you know.

As for "Vitals," see you on the next round.

And please hit us up on our socials.

We'd love to hear from you.

- And if you haven't already, make sure you hit that subscribe button, push the like button, hit the bell for notifications, hit all the buttons.

We will see you soon.

(upbeat energetic music)