PEPFAR, the President’s Emergency Relief Plan for AIDS Relief, is a roughly $7 billion annual program launched in 2003 by the George W. Bush administration to tackle the global HIV epidemic. It is one of the largest and most effective global health programs in history. It is estimated to have saved 25 million lives so far through HIV and AIDS treatment and prevention, and some 20 million people alive today depend on medication from the program.

And now its future is at risk. Rather than meeting a September deadline to reauthorize PEPFAR, House Republicans and Democrats have been in continuing disputes about the program’s funding of organizations that also provide abortion and abortion-related services. The standstill has already lasted several months and has continued into the new year.

That might not seem surprising. Congress was deadlocked throughout much of its most recent session, unable to come to an agreement on an assortment of priorities. And PEPFAR has been subject to criticism in the past — various aspects of the program, such as its support for sexual abstinence programs, its past restrictions on using generic drugs, and the question of funding organizations that didn’t denounce prostitution, have been the focus of debate and legal conflict. But the program has always evolved in the face of criticism and has always been reauthorized with strong bipartisan support every five years — until now.

This standoff risks both the short- and long-term future of the program. The Washington Post reported in October that at least $1 billion in PEPFAR funding for 2024 hadn’t been released because of delays caused by Republicans. But whatʼs even more concerning is that House Republicans have demanded the program move to an annual authorization schedule, which would allow a potential future Republican president to change the details more substantively, and set up even more bruising reauthorization battles.

Without five-year reauthorizations, it’s likely that PEPFAR will struggle to make long-term plans and hires, and appropriations will gradually, and irreversibly, shrink. This would threaten the millions of people who depend on AIDS treatment, as well as the world’s chances of meeting targets to end the global HIV epidemic.

For all these reasons, the fate of PEPFAR may be the most important issue facing global health in 2024.

We’ve forgotten how terrible Africa’s HIV epidemic was

When PEPFAR was launched in 2003, it aimed to prevent 7 million new HIV infections, treat 2 million people with new antivirals, and provide care for the millions suffering from AIDS and children orphaned by it. $15 billion was authorized to be spent over the first five years of the program.

A program at this scale was unprecedented, but so was the magnitude of the AIDS crisis at the time. This was especially true in Africa, the center of the global epidemic, which accounted for over three-quarters of all global HIV cases by 1990. By the year 2000, close to 2.5 million people in Africa were being infected by HIV — which is essentially fatal without treatment — each year, including more than 500,000 children.

By the early 2000s, HIV and AIDS were causing over a million deaths among Africans each year, constituting more than 50 percent of all deaths in Botswana and Zimbabwe. In 2000, almost 9 million African children were orphans from AIDS-related deaths.

Even among those still alive, HIV had spread widely — by 2000, over 5 percent of all people between the ages of 15 and 49 in Africa were living with the virus; 13 percent of adults in South Africa in that demographic were infected, and an astounding 25 percent in Botswana. It had become an existential threat to the future of many countries in Africa.

But Africa didn’t merely face a worse AIDS crisis than the West. It faced a very different one, and as a result, that epidemic would require a very different response. Unlike in the West, the majority of those infected in Africa were women and girls, and in developing countries there was around a one-in-four risk that mothers with HIV would pass on the virus to their children, typically through breastfeeding. In sub-Saharan Africa, where HIV was most prevalent, combating the epidemic would be even more daunting. Over half the population lived in extreme poverty in the early 2000s, and the epidemic itself threatened to deepen poverty further.

And yet, as insurmountable as the crisis appeared, the basis for a solution was already present.

Trials in 1986 for azidothymidine (AZT), the first HIV antiviral drug, were so successful that they were halted early, with just a single death in the treatment group versus 19 in the placebo group. The drug could block HIV from copying itself in our immune cells, and patients saw large improvements within weeks.

Several more highly effective drugs were soon found. By 1996, nine effective antiretroviral drugs had been approved. Each of these drugs was insufficient when taken individually, as the virus could soon evolve to become resistant to it. But when a combination of drugs were taken together, they could mount a substantial barrier to the virus. This new combination treatment, called highly active antiretroviral therapy (HAART), changed the game.

HAART was so effective that it could reduce virus levels low enough to become undetectable. Patientsʼ white blood cells would rebound, and their ability to fight infections would return. It dramatically improved the survival of people with HIV and massively reduced the chances that mothers would pass on the virus to their children. Years later, newer, similar drugs would become components of pre-exposure prophylaxis (PrEP), a regimen someone can take in advance to reduce their chances of being infected.

In short, they were effective beyond what was expected. AIDS-related deaths dropped steeply in the US and other Western countries, as HAART became available to patients. HIV was now no longer a death sentence but had become a manageable chronic condition with treatment.

How PEPFAR largely stopped Africa’s AIDS crisis

Yet these lifesaving treatments were vastly out of reach for the majority of people with AIDS globally.

In the mid-1990s, the regimens had a yearly cost of around $20,000 per person and required multiple doses to be taken each day, at different times, over a lifetime. They also had unpleasant side effects, such as vomiting, anemia, and diarrhea, which meant a sizable share of patients were unwilling to stick to their treatment.

Given that millions of people in Africa had already been infected and faced certain death without treatment — and in some countries, HIV-infected people made up a large fraction of the adult population — treatment had to be a part of the solution. But it remained to be seen whether these therapies could be delivered and taken routinely by people in the poorest parts of the world.

In 2002, President George W. Bush asked a small group of advisers to find out about ongoing efforts and whether it was possible to develop a transformative program, one that could scale up massively across countries.

Bush’s advisers visited Botswana and Uganda, where small-scale programs by groups such as Doctors Without Borders (MSF) and TASO were already in place. These groups were able to provide generic antiretroviral drugs to remote villages, often health care workers carrying them from small clinics in refrigerators. Patients were actively involved in their health and understood the importance of taking doses regularly.

With further data on these programs’ budgets and operating costs, they designed a program that became PEPFAR. They would partner with local governments and communities to build up supply chains, networks, and infrastructure, to scale up the program widely until costs would drop and coverage would take off.

Bush’s initial proposal — for $15 billion over the first five years to support HIV prevention and the treatment of millions of people across 15 countries — was approved with high support from Republicans and Democrats alike. Funding ultimately exceeded the initial proposal by more than $3 billion.

PEPFAR worked with other programs and agencies to bring down the cost of antivirals massively. Through years of price negotiations, investment in health infrastructure, and the development of rapid regulatory review processes for generic drugs, the annual cost fell from the tens of thousands per person per year to just $75 in 2018.

PEPFAR now supports over 50 countries and is one of the most successful global health efforts in history. It’s been able to tackle AIDS through a wide coalition of groups, including local and faith-based communities, scientists, and public health experts, who often disagree on the details and specific approaches to tackle AIDS but ultimately agree that the program is essential.

As great as PEPFAR’s impact has been, it is likely underestimated, because it has also helped build health infrastructure and train health care workers across countries as it has grown, supporting treatment for malaria and tuberculosis, which kill 600,000 and 1.3 million people respectively each year.

In 2022, according to the Joint United Nations Programme on HIV/AIDS, 86 percent of people with HIV worldwide knew their HIV status, 76 percent were receiving antiviral treatment, and 71 percent had virus levels effectively suppressed by treatment. This itself is an immense achievement, but in five African countries — Eswatini, Rwanda, Botswana, Tanzania, and Zimbabwe — all three of those statistics were over 90 percent, meeting UN targets on the path to eliminating the epidemic.

Rarely in global health — or anywhere else — do we see a program so successful. An enormous number of people are getting back control of their own lives, far fewer people are facing a painful and certain death from AIDS-related illnesses, and far fewer children are losing their parents.

Right now, more than 20 million people depend on continued antiretroviral treatment that the program provides. According to a study that looked at the potential impact of disruptions at the start of the Covid-19 pandemic, a six-month disruption in the program would lead to an estimated 88,000 additional AIDS-related deaths, including 52,000 in children.

This means maintaining these efforts is crucial. But the story of PEPFAR is about thinking bigger: that ambitious programs to tackle the biggest problems in global health can be successful.

Even now, almost 9 million people with HIV don’t receive treatment, and over 600,000 still die from HIV- and AIDS-related causes annually. Men, children, and adolescents lag behind in testing and treatment for the disease in many affected countries, and annual funding has recently been declining.

There is still a long way to go — and thatʼs where our attention should be.