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Barbara Lewis will never forget 1996.
"That was the year when people stopped dying,” says Lewis, a physician assistant and HIV specialist at Whitman-Walker Health in Washington, D.C.
For the first 15 years of the AIDS epidemic, which began in 1981, researchers led by the National Institutes of Health (NIH) were desperate to slow the progression of HIV, or human immunodeficiency virus.
They tested high-dose medications such as zidovudine (AZT) and didanosine (DDI) in clinical trials held in major urban areas where people were dying. Lewis, who worked at the AIDS Clinical Trials Unit at D.C.'s George Washington University for 10 years, says people diagnosed with HIV were desperate to get into the studies for a chance of survival.
The drugs, which often came with severe side effects such as pancreatitis and pain from nerve damage, worked for some, but not all. Then, in 1995, a new class of antiretroviral drugs called protease inhibitors became available, and by 1996 AIDS was no longer the leading cause of death in young American adults.
"It was a game changer; ‘96 was the big turning point,” Lewis says.
'Breathtaking’ discoveries change the disease
Some 23 years later, there still is no cure for the disease that has killed 32 million people around the world, according to most recent figures from UNAIDS, the Joint United Nations Programme on HIV/AIDS.
But since the mid-1990s, treatment for HIV with antiretroviral therapy has been “transformational,” says Anthony Fauci, an immunologist and director of the National Institute of Allergy and Infectious Diseases (NIAID), who has been on the front lines of the fight against AIDS since 1984.
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Today, one daily pill — often a combination of three drugs — can suppress the virus to undetectable levels, which allows a person with HIV to live a “relatively healthy, normal life,” Fauci explains. Suppressing the virus to undetectable levels also makes it “essentially impossible” to transmit HIV to a sexual partner. People at high risk for HIV can even prevent infection with a daily pill.
"We've changed this from a disease that was almost universally fatal years ago to a disease that now isn't really even a disease — you can just prevent people from getting sick if you treat them early enough,” Fauci says.
"The area of treatment has been breathtaking in the sense of its effectiveness,” he says.
Breakthroughs notwithstanding, HIV/AIDS research has not slowed. Scientists are testing longer-lasting prevention and treatment therapies that would deliver virus-suppressing medication to patients every few months by injection or implant, “so that people don't have to be thinking about taking a single drug every single day of their life,” Fauci says. “It's fine-tuning, to make it much more user-friendly."
These longer-lasting drugs could be especially beneficial to younger HIV and at-risk patients who aren't used to taking daily pills, Whitman-Walker's Lewis says. Older adults with HIV, however, may already take daily medications to manage chronic conditions, “and if they're very used to taking a pill every day, taking an HIV pill is just no big deal,” she says.
HIV vaccine trials are also underway, but “the big buzz now,” as Fauci puts it, is a national plan that would reduce new HIV infections by 90 percent in the next 10 years. “The way you do that is by aggressively going out, testing people, and those who are infected, treating them immediately” to prevent the spread of HIV, he explains. It also involves making preventative medications available to those at high risk of infection, including people who have an HIV-positive sexual partner or have multiple sexual partners. People who inject drugs or have sex with people who inject drugs are also considered high risk, according to the U.S. Department of Health and Human Services.
Cities such as San Francisco and New York, once epicenters of the AIDS epidemic, have “dramatically diminished” the number of new infections with this test-and-treat approach, Fauci says. Now, the public health community is “working fast and furious” to help other hard-hit cities, counties and states — including Alabama, Arkansas, Kentucky, Mississippi, Missouri, Oklahoma and South Carolina — achieve similar results.
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Working toward a cure
Viral suppression is one way experts are trying to end the AIDS epidemic. Others are working to eradicate the disease completely, by way of a cure.
There are a number of reasons why a cure is needed, says Rowena Johnston, vice president and director of research at AMFAR, the Foundation for AIDS Research. For instance, the emergence of drug resistance could make HIV “increasingly difficult to treat” in the future. There's also the cost of HIV care, which can exceed $379,000 (in 2010 dollars) in a person's lifetime, according to Centers for Disease Control and Prevention (CDC).
Clearing an HIV infection would also clear someone of the stigma attached to the disease. Beliefs that HIV and AIDS only affect certain groups of people — such as drug users and gay men — are rooted in fear from images and misinformation that spread in the early days of the disease, the CDC says. “And as much progress as we've made in the last 40 years of HIV, there really is still a significant stigma attached,” Johnston says.
Discovering a cure may seem like a lofty goal, but 2019 has been a “really exciting year” in terms of progress made, Johnston says. Researchers have been following a few cases in Europe where people living with HIV received bone marrow transplants to cure cancer. In both cases, the donor stem cells had a genetic mutation that blocks the HIV virus from entering the cells. Both patients were cured of their cancers, and HIV was wiped from their bodies.
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These findings are “truly pivotal,” Johnston says. “For the first time, we knew it was actually possible to cure HIV. There is a scientific basis for believing that a cure is possible, and we have one route by which that can be achieved.”
However, performing costly and complicated bone marrow transplants on people infected with HIV is not a realistic way to cure populations around the world. Rather, the findings from these cases point to “promising avenues” that can be adapted in a clinical setting, Johnston says.
One of these avenues is gene therapy — an experimental technique that uses genes to treat or prevent a disease by replacing disease-causing genes with healthy ones, according to the NIH.
In the case of HIV, Johnston says researchers could potentially “snip out” part of the DNA that allows HIV to enter and infect cells, and replace that gene with the mutated version that blocks the virus. Then the edited cells are transplanted back into the patient. “And the good news is, there doesn't seem to be any deleterious effects of doing that,” she adds.
Experiments with gene therapy have shown promising results in treating people with sickle cell anemia and cancer. Johnston predicts clinical trials testing the technique's effectiveness with HIV are “a couple of years away.”
"It's a question of optimizing technology that already does exist, so we're not making up things that don't yet exist,” she says.
Since the AIDS epidemic hit the U.S. nearly four decades ago, finding ways to treat and cure HIV has been nothing but challenging. But 40 years from now, Johnston says, having a cure for the disease “doesn't seem unreasonable.”