people in 2018. Since the early days of the epidemic, the virus itself has confounded

researchers, who have long been searching for a vaccine to prevent its spread. And after

years of slow progress, that search may soon be over.

The epidemic as we now know it, is thought to have started in the mid-to late 1970s,

but it wasn’t until 1983 that the HIV virus was first identified and isolated. By that

point, HIV had begun to rapidly spread around the world—and since the epidemic began,

it’s claimed the lives of over 32 million people.

To understand why this virus causes so much harm, we first need to know how it invades

the body. First off, it’s a retrovirus, which is a type of virus that inserts a copy

of its genome into the DNA of a host cell — in HIV’s case, T-helper cells which

help our immune system fight off infection. After latching onto the cell, HIV fuses with

it, integrating its genetic information with the new host’s DNA. The infected cell then

produces more HIV proteins, which are eventually released into the bloodstream where they continue

to replicate. If left untreated, HIV severely weakens the immune system’s ability to function

properly—this final stage of the infection is AIDS.

And it's precisely the virus’ unique characteristics which allow it to propagate inside the human

body that also make it so difficult to tackle. “HIV is a remarkably small virus. It has

few genes comprised in it, regardless of how small and simple it may be, it has very complex

dynamic interactions with the human immune system.”

There’s currently a few ways to stop HIV from progressing in its life cycle. Specific

drugs have been developed that can stop the virus from attaching to T-helper cells, while

other types of drugs work to prevent the virus from taking control of the cell’s nucleus

and enter the bloodstream. Called antiretroviral therapy, or ART, this drug combination works

well, but is expensive and requires lifelong upkeep.

“In those resource constrained areas or where the stigma of HIV is still a major problem,

prevention methods that require daily pills may still limit the number of individuals

who would have access to these. It’s only through the application of very highly effective

vaccines that we've been able to control an infection that spread around the globe, and

eventually eradicate that.” But that doesn’t mean developing a vaccine

is easy. There aren’t many good models to reference for research in humans, which means

we don’t know what the body’s immune response looks like when trying to protect itself.

HIV’s extraordinary diversity and ability to rapidly mutate are also huge obstacles

in getting a grip on the virus. Just recently, researchers announced that they’d ID’ed

a new strain, the first in 19 years. Despite this, there has been huge progress made in

the last decade. In 2009, researchers declared that a vaccine

trial done in Thailand had protected a significant minority of humans against the disease for

the first time ever. RV144, is a combination of two genetically engineered vaccines, neither

of which had worked before in humans. “We observed a modest level of efficacy

over three and a half years—about 30%. So, we have initiated a clinical trial in South

Africa that is marching along the path to try to confirm these findings from the Thai

trial and extend those findings through a number of approaches.”

As the world’s largest publicly-funded international collaboration focused on the development of

vaccines to prevent HIV and AIDS, HVTN has conducted all phases of clinical trials that

have involved thousands of people. In addition to two massive trials to test whether giving

antibodies to patients can protect them from HIV infection, as of this year the group has

also fully enrolled two similarly ambitious vaccine trials. Called HVTN 702 and 705, these

regimes were designed to test whether patients given a vaccine can create antibodies on their

own. Both vary slightly in their approach— 702 is based off of the Thai trial, while

705 is focusing on overcoming the viruses’ genetic diversity.

“What's very exciting is that the immune responses elicited by these three different

vaccine strategies is different within each clinical trial, but there's similarities across

them. And we're looking for specific immune responses that we will correlate with vaccine

efficacy, with just a few dozen people that will eventually lead us to a more globally

effective vaccine that could be used across different populations and routes of exposure.”

With hopes high, and even higher stakes, the mood of the vaccine research seems to be one

of cautious optimism. But results of both the 705 and 702 vaccine regimes won’t be

in until late 2021 and 2022, when the trials are expected to close.

“They will certainly be a success and that will get a clear answer as to whether or not

these vaccines worked, but I think we also have to be measured in our expectations. And

that this is one of the most formidable biomedical challenges we've ever undertaken as a society,

as a global research community.” If you want to learn more about the search

for a potential HIV cure, check out this episode of How Close Are We. If you liked this

video, let us know down in the comments and don’t forget to subscribe for more Seeker.

As always, thanks for watching, and I’ll see you next time.