Ending AIDS: HIV,ART,and PrEP in the Context of New Global Political Realities

In a commentary last year, I stressed that the persistent failure to meet United Nations Programme on HIV/AIDS (UNAIDS) targets for HIV incidence and mortality cannot be attributed to deficits in knowledge or absence of effective antiretroviral treatments (ART) and potent biomedical prevention interventions. ¹ “We know what enables success. … The path that ends AIDS is not a mystery. It is a political and financial choice,” Winnie Byanyima, Under-Secretary-General of the United Nations and Executive Director of UNAIDS, admonished. ² She emphasized that many regions worldwide are not allocating sufficient and sustainable resources to mount effective responses based on existing strategies, and certainly not with regard to new breakthroughs involving long-acting injectable (LAI) ART and HIV pre-exposure prophylaxis (PrEP). In the current political climate, this is only likely to get worse.

Dr. Chris Beyrer, Director of the Global Health Institute at Duke University, summarized impediments to even a guarantee of stability in addressing the HIV pandemic—continuing a slow decline in HIV incidence and mortality in many areas of the world—in his plenary presentation at the recent 32nd annual Conference on Retroviruses and Opportunistic Infections. ³ And there is little assurance that resources to intervene in the epidemic expansion currently characterizing eastern Europe, Central Asia, Latin America, the Middle East, and North Africa will be available.

Beyrer first acknowledged an important trend: global cumulative HIV PrEP uptake has increased every quarter since its introduction in 2017, from a few hundred thousand to almost 8 million HIV at-risk individuals by 2024. PEPFAR, the President’s Emergency Plan for AIDS Relief, was responsible for covering about 60% of PrEP funding in 2021 and over 80% by 2024. However, since 2012, the number of people acquiring HIV in eastern and southern Africa has exceeded the number accessing PrEP in those regions by the ratio 1.5:1. Even more discouraging is the picture in eastern Europe and central Asia, where, since 2012, the number acquiring HIV has exceeded the number accessing PrEP by the ratio 42:1. In most regions of the world, PrEP uptake is far too low to prevent new infections.

A UNAIDS goal of controlling the HIV epidemic by 2030 is rendered additionally problematic in areas of low to medium HIV incidence, defined as <3% of the population: 200 individuals would need to utilize PrEP to prevent a single HIV infection. More than 40 million people need to be on PrEP to reach epidemic control, an unrealistic goal even with stable PEPFAR funding. PrEP combined with sustained HIV suppression utilizing LAI ART could end AIDS, but only if taken to scale for both high-incidence-density populations—men who have sex with men, sex workers, and transgender individuals—and lower-incidence ones. ³

The above interventions assume not simply access to oral PrEP but also adherence. Compliance is particularly low among young African women, with only about 20% continuing for up to 6–9 months. ⁴ Large, randomized trials of different interventions have not demonstrated improved adherence in this population. ⁴ The authors of one such study concluded that “Future research is needed on whether and how to scale-up PrEP support for young women in resource-constrained settings.” ⁴

A different issue complicates reliance on ART in terms of individual health and the undetectable = untransmissible paradigm. UNAIDS advocates for placing equity in access to ART and HIV health care at the center of efforts to end the HIV pandemic. But, as demonstrated by a recent modeling study from Malawi, extreme geographic misalignment of HIV health care resources, leading to HIV “treatment deserts,” is not uncommon in sub-Saharan Africa, where 25.5 million people live with HIV. ⁵ About 23% of people living with HIV in Malawi reside in such deserts, defined as having to walk up to 3 h to reach a health care facility, and those facilities receive only 3% of the nation’s supply of ART. ⁵

Ominous trends in the “Southern Region of the US,” encompassing six states and Washington, DC, and accounting for more than 50% of all HIV diagnoses in the US, ⁶ illustrate a key counterpoint. Some public health initiatives there are advocating for focusing prevention efforts solely on non-disproportionately affected (NDA) subpopulations such as pregnant women, infants, first responders, and human trafficking victims, even though those groups represent only 2% of diagnosed HIV cases. ⁵ In contrast, prevention efforts aimed at disproportionately affected (DA) versus NDA populations could reduce new infections across the Southern US Region by 47% versus 1%, respectively, by 2030. ⁶

This information is daunting enough without the confounding fact that PEPAR prevention programs are on pause. Per President Donald Trump’s executive order, on January 24, 2025, the US State Department issued a stop order freezing all foreign aid programs, including PEPFAR. It was modified by a subsequent waiver for “life-saving HIV care and prevention programs to prevent vertical transmission” of HIV, with PrEP offered only to pregnant and breastfeeding women. ⁷ Based on a conservative model, a 90-day pause of such coverage could result in excess of 100,000 HIV-related deaths over the subsequent year. ⁷

Which is curious, given that in 2019, during his first term, President Trump initiated an important initiative with a mandate to end the US HIV epidemic by 2030 through a focus on DA: 57 jurisdictions with the greatest need. Three years later the plan had suppressed new infections by 30% in adolescents and young adults and by 10% in most other groups. ⁸ As one PrEP advocate noted, “it doesn’t seem like the current administration is motivated by prior accomplishments.” ⁸

What might be done about all of this? As Dr. Beyrer recently wrote, strident acknowledgment of these issues to underscore the urgency for population-based control of HIV globally is required. ⁹ Expansion of health budgets within affected countries will be necessary. Oluremi Tinubu, First Lady of Nigeria, declared that “Africa cannot continue to rely solely on donor funding and foreign aid, which, although helpful, are often unpredictable and unsustainable.” ¹⁰ As noted by Dr. Deqo Mohamed, director of a hospital and mobile clinic in Somaliland, “Somalis are sometimes reluctant to pay because they are so used to getting free medical services from foreigners.” That mind-set is part of what needs to change. ¹¹ And new paradigms enabling public health programs to remain effective, nationally and internationally, perhaps with companies directly negotiating with states, countries, and nongovernmental organizations, and involving local expertise and resources, will be required. ^{8 , 10} The potential for just once a year injection of a LA PrEP product, based on recent phase 1 studies in the U.S. ¹² can overcome several of the obstacles discussed above. But, as stressed by two health public health experts from South Africa, this will be highly dependent on industrial cooperation. “Currently, pharmaceutical companies are consigning an entire generation of people to lifelong infection and treatment, in a macabre slow dance around price and patents.” ¹³