After 20 years a massive U.S. government effort has reached a new milestone in its battle to defang the global HIV/AIDS epidemic: this past March the Centers for Disease Control and Prevention announced that by 2022 the U.S. President's Emergency Plan for AIDS Relief (PEPFAR) had provided lifesaving antiretroviral therapy to more than 20 million people around the world with HIV—a 300-fold increase from the 66,500 people the program treated in 2004.
PEPFAR's progress has shown that halting a deadly and intimidating global epidemic isn't impossible. Since the George W. Bush administration launched the ambitious plan in 2003, PEPFAR has funneled more than $110 billion into HIV/AIDS treatment and resources. It's the largest concerted public health effort by any one nation to tackle a single disease and has been credited with changing the global course of HIV/AIDS, a devastating illness that was once considered terminal.
The year PEPFAR was announced, the World Health Organization reported an estimated 40 million people were living with HIV. Countries in sub-Saharan Africa, where the epidemic was the most severe, had the majority of cases, with an estimated 26.6 million people infected. Most of Africa's health-care facilities and universities lacked resources for the testing, drug administration and monitoring needed to care for such large numbers of patients. In many parts of the continent, HIV/AIDS simply was not a survivable disease, says Phyllis Kanki, a professor of immunology and infectious diseases at Harvard University.
“We previously have had global health problems where diseases affect all populations.... But HIV was a more dramatic scourge of a pathogen because it was killing so many people, and there was no therapy,” says Kanki, who helped to start the AIDS Prevention Initiative in Nigeria in 2000 and served as principal investigator for Harvard's PEPFAR program from 2004 to 2013. “I think PEPFAR has provided the solution to what was not a livable and survivable disease for scores of people who never would have had access to [HIV drugs] in the past. I think that was the big change and why it will be heralded as a huge global health success story.”
Scientific American spoke with Kanki to understand how PEPFAR helped to treat millions with HIV/AIDS, how the program could inform other worldwide health crises and what stubborn barriers remain to ending the global HIV/AIDS epidemic.
[An edited transcript of the interview follows.]
What was the state of the HIV/AIDS epidemic in Africa in 2003?
In many parts of Africa, they had already been describing cases in the mid- or late 1980s. It was already appreciated at that time that there were parts of the continent that were heavily burdened, such as Botswana, South Africa—those places were already documenting 20 to 25 percent infection in the general population.
I think there was a general recognition that unlike in the U.S. and Europe, where HIV infection was mainly seen in certain risk populations (and at that time it was probably intravenous drug users and men who were having sex with men), in sub-Saharan Africa, it was a much more heterosexual, young adult population. So it was harder to target who really was at risk for being infected. That was a real concern because you didn't have good programs and infrastructure set up to rapidly diagnose these people and put them on a complex therapy even if that therapy was available to you.
There was a lot of variability on the continent, but generally there weren't many accessible programs for people to receive drugs if they found out they were infected with HIV. Those with means who found out they were positive might have to pay huge sums of money to get drugs or go to Europe or the U.S. for treatment. But that was certainly just a small proportion. There were not known government programs that were readily set up to help people. And that was particularly true in places that were hardest hit and had what was already known to be the largest proportion of infected individuals.
Why was PEPFAR started?
As a minimum standard of care, you have to have a good diagnosis; you have to be able to bring in the drugs—the drugs all have to be there; you have to give the treatment to patients every month; you have to have a system so you know you're giving it to them; and then you have to have a way of monitoring them. And none of that was in place.
One of the reasons it was such a challenge for people in international health to grapple with HIV is that it was such a complicated disease. It's hard to diagnose. You can't treat somebody if you don't know they have it. Then once you put somebody on treatment, it's lifelong. At the time, patients were having to take six to 12 pills once, twice, three times a day. And it's absolutely critical that they take the pills every day because if they stopped, the viruses that are still in their bodies would become active again, and they can get sick and could die. Some pills require refrigeration. Some pills you couldn't take unless you had already eaten a meal. In some of our clinics, if populations were food-insecure, we had to provide food. And you have to monitor people with tests that most of the labs or university hospital facilities didn't have the equipment for. Who was going to pay for these tests? You couldn't ask patients to pay, and you couldn't ask labs that didn't have the equipment to run the test.
We also had problems in some populations in Africa where there was a lot of comorbidity—another disease you see with HIV is tuberculosis [TB], which a real killer all by itself. You had to deal with managing two different therapies for two different complex diseases.
Around that time, the government of Nigeria had tried to purchase generic drugs in India to provide treatment for some of the first HIV-infected individuals, recognizing it had a huge population that was already infected. They started the government program, but it was very small. Governments in Africa had already tried to begin these programs, but PEPFAR was a shot in the arm. We were able to use PEPFAR funds to really bolster what was just the beginning of Nigeria's program.
Today PEPFAR works in more than 50 countries, providing health-care infrastructure and resources—including antiretroviral therapy (ART)—to stymie the spread of HIV. What is ART, and how has it transformed HIV/AIDS care?
The virus itself enters a key cell that's important in defending your body from outside pathogens, and that cell is the lymphocyte. It's one of your white blood cells that circulates through your body and in certain organs. It's a key player in protecting you. So one of the villainous properties of the virus is that it integrates; it inserts its genetic material into yours. And that's why an infection with a retrovirus such as HIV is forever—because you can't get rid of it.
There are different classes of ART drugs that operate on different parts of the virus's life cycle. Some will basically stop the virus before it integrates. Other drugs inhibit the integration step. Others block the virus's entry into cells.
When we started out, we showed slides of people with two hands together with a pile of pills. Currently it's probably one pill a day—that's a single pill that includes multiple drugs. Those pills are much more effective than what we were able to give out before. So things have really changed in 20 years.
What's on the horizon for HIV/AIDS treatments?
There's PrEP (pre-exposure prophylaxis): if you're uninfected, this pill will help prevent you from being infected by another individual. There are different modalities and ways we would use these very effective therapies to try to limit spread or to decrease virus so that people don't get sick. There's a continued effort to develop a vaccine.
There's a lot of research being done on what's called the HIV cure [a few people reportedly have been cleared of HIV or considered to be in long-term remission after receiving HIV-resistant stem cells] and different ways that researchers think they can try to get rid of the disease. But certainly that's still a work in progress, I'd say.
What disparities and stigma still exist around HIV/AIDS? What efforts are there to identify those who need treatment and make sure they can access it?
There's stigma with a lot of different diseases, but we see in Africa that people don't want to be known to have HIV infection, because maybe it carries the stigma that they had multiple sex partners or had used drugs. Even just that you're not healthy—that can be a stigma in certain populations.
We've been involved with projects for men who have sex with men in Nigeria, and that's a very stigmatized population. It's very hard for them to identify and find supportive clinics, which are quasi-underground, to be able to get access to the care. That's partially because there are laws in those countries that criminalize their sexual orientation.
Africa has the largest number of kids who were infected at birth. Those kids are growing up, and many of them are stigmatized—they're 12 years old, and they've just been told by their mother that they've been taking pills, and those pills are for HIV. They don't want their classmates or other people in the community to know that's what they have because it reflects badly on them and also on their family. So then they don't want to go to the clinic and be seen. We do have problems with adolescents when they're grappling with a lot of other issues in their life and having to deal with the fact that they're supposed to go to a clinic every month that identifies them as having HIV. They're going to have to do that for the rest of their life.
What do you think are the major next steps to reaching PEPFAR's goal of ending the HIV/AIDS epidemic as a public health threat by 2030? How realistic is it?
A lot of these international goals are kind of pies in the sky, but you have to keep going. You can't stop when you're 10 feet from the goal line. Many countries are very close to providing treatment to every person with HIV. I think Botswana, for example, is very close. It has a large infected population but has been very successful in identifying and treating all the people who are affected. And the goals to prevent infection and to treat every pregnant woman who's positive can really make a difference in getting rid of infant HIV infection because that's a starting point.
What lessons from PEPFAR could be applied to other epidemics or disease-prevention strategies?
It was a brand-new approach to a global health problem. I think PEPFAR was different because it committed such a large amount of money to one disease, primarily in parts of the world that were most affected—those that were the poorest parts that would not have been able to do anything at that time with what was available. PEPFAR was really the ambulance with the medicine. The size of it and the scope of it were so huge. Those of us who were working in Africa were kind of amazed at the idea that a U.S. program would commit so much money to people in Africa. We were happy about it, of course. We had never seen anything like it. So it was really a tremendous opportunity, and no one knew whether it would really work. And 20 years later we see that it did. It really made a huge difference for health care overall, not just HIV care, in all of these countries.
AIDS is caused by one virus, but it affects other things such as TB. So I do think the PEPFAR program provided a lot of important lessons for how we could deal with the Global TB Program. It did bolster the infrastructure that was available for TB, and it certainly improved care for that. Many of the labs that were developed for providing HIV services have been used for things such as Ebola and mpox. I think all of that has a trickle-down effect of improving health-care services overall.
And that's why I think PEPFAR will be recognized for many additional benefits that are outside of just dealing with the horrible issue of the HIV pandemic and AIDS. Many other health-care problems were addressed on the side. We're in a better position to deal with HIV than we were in 2004, for sure.