HIV is not 'solved,' and a doctor who treated the first patients still hopes to ultimately bring a cure

In 1981, when Dr. Marcus Conant identified early warning signs of a new disease affecting the gay male community in San Francisco, he was optimistic that a solution would not be far off. More than four decades later, despite numerous therapeutic interventions, the AIDS epidemic persists, and Conant still has a significant stone unturned in his illustrious medical career: finding a cure.

Now 87, Conant serves as Chief Medical Officer at the biotechnology company American Gene Technologies. He did not initially enter medicine with the goal of unraveling this major infectious disease puzzle. He started as a dermatologist, also treating genital herpes—but in the early 1980s, when he identified Kaposi's sarcoma lesions on his patients' skin, he began to see a connection to an emerging health crisis primarily affecting gay men.

"Like many epiphanies, it didn't happen suddenly," Conant said. "It was over time, and then one day you wake up and realize, wait a minute—this is now my life."

For Conant, this path has been challenging both scientifically and emotionally. He has witnessed the failure to develop an HIV cure over nearly half a century, while many of his patients and friends have died from the disease.

"I enjoy health, both mentally and physically, which is a blessing, and I love what I do," Conant said. "But I've had to watch beautiful, intelligent 35-year-old men die, so as long as I'm still healthy and able to do this, it's what I should be doing, and I'll continue to do it."

Conant's vision of an AIDS-free world remains elusive given the many obstacles that still exist. But as the biopharmaceutical industry gradually moves closer to providing long-term solutions for HIV patients, his long-term work on the front lines is invaluable to that effort.

"Most people think we've conquered it, think it's no longer a problem—people can take pills, but they overlook the fact that the number of infections is rising."

— Dr. Marcus Conant, Chief Medical Officer at American Gene Technologies

Then and Now

According to HHS data, more than 700,000 people in the U.S. have died from HIV since 1981, with over 1.1 million people living with HIV recorded last year. The global numbers are even more staggering—WHO estimates that over 600,000 people die from the virus annually, with approximately 1.3 million new infections in 2022.

Despite the massive loss of life and scale of infection, leading pharmaceutical companies have developed combination therapies that allow people with HIV to survive. The FDA last week approved a new indication for Gilead Sciences' Biktarvy to treat patients with treatment-resistant HIV. Gilead also has a variety of other treatments and pre-exposure prophylaxis (PrEP) options for individuals at risk of infection.

Similarly, GSK's ViiV Healthcare, in collaboration with Johnson & Johnson, developed Cabenuva, an injectable that patients only need once every two months to maintain an undetectable viral load. Long-acting options like this are currently the closest thing to a cure.

But it hasn't always been this way, and Conant has witnessed the introduction of every new therapy. Journalist Randy Shilts documented the roles of Conant and many others in his acclaimed 1987 book "And The Band Played On: Politics, People, and the AIDS Epidemic." From identifying the disease in San Francisco to fighting for recognition from lawmakers and the broader medical community, the early years were filled with confusion and danger, not to mention a treacherous political minefield.

Conant remembers what Shilts told him when he tested positive for HIV in the mid-1980s.

"I remember him saying, 'If you guys don't hurry up, I won't make it,'" Conant recalled. "And what we didn't realize at the time was how prophetic his words were—when we finally got highly active antiretroviral therapy, it changed everything."

Shilts died of HIV complications in 1994.

The turning point began with the antiretroviral drug AZT—developed by GSK before it adopted its current name—which received FDA approval in 1987, becoming the first treatment for HIV. But it wasn't until 1995 that protease inhibitors became available, and the results were "so overwhelming that we called it Lazarus syndrome, because people were rising from the dead."

These treatments came too late for Shilts and many others, but since then, a fact has been established: an HIV diagnosis is no longer a death sentence.

Where Is the Cure?

By 1987, there had already been attempts at an HIV vaccine, Conant said. But rather than giving researchers hope, these efforts confirmed that this was a more complex virus than previously thought.

"At first, we thought this was an infectious disease like all others, and we would have answers soon," Conant said. "But those early vaccine attempts reinforced the idea that we wouldn't easily conquer this thing—42 years later, we still haven't."

Conant says public awareness of HIV and AIDS has waxed and waned, and while the availability of treatments has been extremely beneficial to patients, it has also fostered a mindset that hinders research into more effective solutions.

"Most people think we've conquered it, think it's no longer a problem—people can take pills, but they overlook the fact that the number of infections is rising," Conant noted, adding that many treatments only work for a subset of the population, and the virus often develops resistance over time, leading people to infect others unknowingly.

"One of the problems is that about 40,000 people in the U.S. have exhausted all available drugs. So what's next? What's the next drug? What do we do next?" he said.

American Gene Technologies, where Conant serves as Chief Medical Officer, is one of the companies seeking what could become a cure for HIV and AIDS, with a focus on gene therapy AGT103-T. The treatment has passed early clinical trials with good safety and tolerability and is now entering the second part of the study, with preliminary efficacy data showing blood markers in five enrolled patients.

However, gene therapy is expensive. Approved therapies in other areas often cost over $1 million, and given the nature of HIV, such a price would severely hinder patient access, at least initially, Conant said.

"With gene therapy, in my view, cost is one of the main problems we face because at this stage of development it's extremely expensive. We know costs will come down, but in the early frontier of this technology, the cost is truly prohibitive, and you have to find people willing to take risks and invest," Conant said.

Beyond AGT, there are more potential cure options in the pipelines of academia and industry. Companies like ViiV have initiated projects using antibodies and gene induction to achieve complete viral suppression. Last year, Gilead's Chief Commercial Officer told PharmaVoice that the company is studying its HIV treatment Sunlenca as a twice-yearly preventive, and if successful, the drug could "end HIV."

But some hopes have also been dashed. Johnson & Johnson's promising HIV vaccine program failed despite reaching late-stage trials. Last year, the pharmaceutical giant terminated its Phase 3 study due to lack of efficacy, showing that even the most well-funded programs can fail.

Nevertheless, in 2024, Conant is not certain a cure will be available by 2030—a goal set by many organizations, including WHO and HHS. Over his decades of experience, Conant has seen countless deadlines come and go.

"In 1985, the chief researcher at NIH got up and said we would find a cure for this disease within two years," Conant said. "They always give an idealized date, usually about 10 years ahead of the actual timeline, and unfortunately, I don't see any data suggesting we'll achieve it before [2030], even though many other very dedicated people are working toward it."

A large part of the problem is that the challenge is not just medical, Conant said. Social and political factors heavily influence efforts to reach patients for education, testing, and treatment.

"We've never eliminated any epidemic through treatment alone—to stop an epidemic, you not only have to treat the infected, but you must also protect the uninfected," Conant said. "For example, in a measles outbreak, you can treat all measles patients, but unless you vaccinate people and protect them from the virus, you can't stop a measles epidemic."

Despite the array of treatments offered by top pharmaceutical companies and increased education, HIV remains an epidemic more than four decades later.

"Yes, we've educated people to get tested, to get treated, and the public now thinks the problem is solved and we don't have to worry anymore," he said.

'Disease of the Deviants'

Conant knew early on that ending AIDS would involve more than just finding a medical solution. As a gay man who moved to San Francisco in the 1960s to pursue his career without condemnation, he saw two Americas, and the new virus of the 1980s made that even clearer.

"After the Summer of Love, sexually transmitted diseases in the Haight-Ashbury [community] were a normal course of events for doctors working in that area and community," Conant said. "But when you looked at the rest of America, this wasn't a disease of young people—it was a disease of 'deviants,' and we had to treat them that way."

Back then, anger drove Conant's relentless pursuit of understanding the virus.

"What kept me going? It was anger, anger at the rest of my country for not understanding that these were their sons dying," Conant said. "They treated these people like criminals."

The U.S. was not the only country where homophobia influenced decisions in the HIV field. Shilts' book recounts a trip Conant and other researchers took to Japan to discuss the issue, where Japanese officials believed AIDS would never be a problem because their country had no gay people. Similarly, when Conant testified before Congress in the mid-1980s, he remembers then-Assistant Secretary for Health Dr. Edward Brandt telling him, "I've never met a homosexual."

As the political environment around LGBTQ issues has evolved, Conant says prejudice still exists, even if officials are more cautious about it.

"Those prejudices... don't disappear," Conant said. "We wouldn't have had this epidemic that has killed 40 million people and infected another 40 million, because the handling would have been different—not just in this country, but worldwide."

From Here to There

Biopharmaceutical companies have recognized over time that a single drug is less effective against HIV than combination therapies. And developing these combination therapies requires collaboration between companies that hold their own intellectual property to have a lasting effect on patients.

"A pharmaceutical company might have an effective drug, and they realize that unless they partner with another company that has proprietary rights to another drug, we don't have a marketable product," Conant said. "So what drives collaboration is, unfortunately, economic interests—they have to collaborate, or they can't sell what they have."

In essence, the nature of HIV has forced companies with competing interests to collaborate for solutions and even future cures, Conant said.

Government intervention is also important in facilitating interaction and cooperation among drug developers, he said.

"There are times when we need to collaborate, and capitalism may not give us the answer, in which case the government should step in and say, 'We'll compensate you so you don't lose money developing these drugs,'" Conant said. "If the government said this is such a threat to a segment of the population, we will... reward [companies] for collaborating, collaboration could have happened faster."

Although Conant doubts that a true cure—and access to it—will take longer than a few years, he also sees hope on the horizon after years of ups and downs.

"How do we stop the AIDS epidemic? We already have all the tools now, but to truly stop it, we must find and treat every positive person and protect every negative person," Conant said. "It's very complex, and unless you do those three things, you will fail—but I intend to keep moving forward."