One of the great pandemics in human history has been fought to a near draw, with no vaccine in sight but treatments that dramatically extend life and block transmission to others.

Twenty-five million global deaths later, there is cause for some well-earned, tempered optimism on HIV/AIDS.

Giving this forecast considerable credibility is the man delivering it: Anthony Fauci, MD, director of the National Institute of Allergy and Infectious Diseases at the NIH. Fauci has been involved in HIV prevention since the virus first appeared in the U.S. in 1981.

Almost four decades later, he is optimistic — with a quick caveat.

“I’m somewhat reserved on how we’re going to get to the end game, but the reason for the optimism is that we now have the tools — which have been proven in a variety of clinical trial settings — that can give you the ammunition, if implemented in an aggressive and sustained way, to actually turn around the trajectory of the epidemic,” Fauci said in a recent podcast by the CDC.

Current therapies can reduce the virus to essentially undetectable levels, he explained.

That’s not a cure in the traditional sense, but it enables those living with HIV — once a universal death sentence — to have ever-increasing lifespans. “You can essentially save the life and prevent illness in the individual person,” he said.

“We also know that, when you decrease the level of virus to below detectable level, it makes it virtually impossible for that person to transmit the virus to someone else. We call that ‘treatment as prevention.’”

There are now more ways to prevent HIV in high-risk people, including pre-exposure prophylaxis (PrEP) in a single pill.

“The efficacy of that is well over 95%,” Fauci said.

Theoretically speaking, these medical breakthroughs mean if all the people with HIV were under treatment and all of their sex partners on PrEP, sexual transmission stops.

The real-world problem is implementing such an approach not just in industrialized countries, but in regions with insufficient healthcare infrastructure. “You can certainly do it in select places,” Fauci said.

“So, that’s the basis for the optimism, that it can be done. But we have an ‘implementation gap.’ We have the tools, but we really have not been able to fully implement them to the degree to get the effect that we want.”

The holy grail of HIV research remains the creation of a vaccine. It has been elusive and remains so.

For other infectious diseases that have highly effective vaccines — smallpox, polio, measles — natural infection generates a strong immune response in the human body, he explains.

“That’s the fundamental basis of a ‘proof of concept’ — that a vaccine can induce a response that ultimately would be protective,” he said.

“That’s why we were confident that sooner or later we would get vaccines for smallpox, for polio, for measles, and other pathogens. With HIV, it’s a different story.”

For reasons that are not completely understood, the body does not have a very good natural immune response against HIV.

“It certainly makes an immune response, but it doesn’t, on its own, suppress the virus, and it doesn’t certainly eradicate the virus,” he said.

“When you’re making a vaccine, the best thing to do is to mimic natural infection, without hurting the patient.”

However, efforts to mimic natural HIV infection do not generate the needed immune response to create a vaccine.

“We have a major challenge with an HIV vaccine,” Fauci said.

“[Which] is to make a vaccine that would be doing even better than nature could do — to induce a response that’s even better than what natural infection induces.”