This week’s issue covers the latest developments in the AVAC vs. Department of State lawsuit, NIH’s termination of vaccine hesitancy research, new data revealing the deadly impact of foreign aid cuts on HIV, and renewed calls for African-led, sustainable health funding. Read on for more.

AVAC vs. Department of State

On Monday, US District Court Judge Amir Ali issued a 48-page ruling in AVAC vs. Department of State and Global Health Council vs. Trump, the twin lawsuits against the foreign aid freeze. The ruling orders the government to pay for work already completed and to spend congressionally appropriated funds for foreign assistance. However, Judge Ali’s order did not reinstate the mass cancellations of aid grants, leaving thousands of lifesaving programs in limbo. Lauren Bateman, lead counsel on AVAC’s case with Public Citizen Litigation Group, said “Today’s decision affirms a basic principle of our Constitution: the president is not a king. But we are painfully aware that, without unwinding the mass termination of foreign assistance awards, winning on the constitutional issues does not avert the humanitarian disaster caused by the Trump Administration’s freeze on foreign assistance. And it does not undo the damage that the freeze has already inflicted on millions of vulnerable people across the world. Deaths will continue to mount. While the courts have an important role to play in standing up for the rule of law, Americans need more than just the courts. We need Congress, which has always supported foreign aid on a bipartisan basis, to assert itself.”

IMPLICATIONS: Secretary of State Marco Rubio confirmed that 5,200 USAID programs—about 83% of the agency’s overall work—have been terminated, citing “tens of billions of dollars” spent in ways that allegedly “did not serve US interests”. The new administration will retain about 1,000 programs under the State Department’s oversight. Even if some contracts are eventually reinstated, the State Department has already eliminated a significant majority of USAID’s work and tens of billions of dollars in Congressionally approved spending. It is unlikely implementing partners and programs will receive the funding they need to start back up and continue their critical work.

FOLLOW ALONG: Visit our updated page summarizing the lawsuit.

READ:

• Judge orders Trump to pay USAID partners, rejects ‘unbounded’ power—Devex  
• Trump Avoids Worst-Case Ruling in Lawsuit Over USAID Defunding—Bloomberg 

NIH Cancels Grants on Vaccine Hesitancy

In a sweeping move, the National Institutes of Health (NIH) is terminating or scaling back dozens of grants focused on vaccine hesitancy and boosting vaccine acceptance, citing “misalignment with NIH funding priorities.” It is unclear whether new Department of Health and Human Services (HHS) Secretary, Robert F. Kennedy Jr. directed the cuts—his longstanding anti-vaccine views are concerning, especially since the Centers for Disease Control and Prevention (CDC) was recently instructed to revisit the debunked link between vaccines and autism. The NIH is also canceling grants tied to transgender issues, diversity, equity, and inclusion, and research involving Chinese institutions, reflecting the administration’s broader push to cut spending and reshape federal research priorities. 

IMPLICATIONS: Defunding these projects comes at a perilous time, given the reemergence of measles and declining immunization rates. By terminating research on vaccine hesitancy and acceptance, the NIH undermines efforts to build trust and increase uptake of essential prevention strategies, particularly among marginalized communities. This short-sighted approach risks widening existing health disparities and eroding decades of global progress toward equitable HIV prevention. 

READ:

• NIH to ax grants on vaccine hesitancy, mRNA vaccines—Science
• NIH to terminate or limit grants related to vaccine hesitancy and uptake—Washington Post

Reforming PEPFAR

Researchers are proposing strategic reforms to PEPFAR, which is up for reauthorization later this month. The recommendations would trim PEPFAR program costs by 20% in five years, and transition financial responsibility to local governments in high-burden regions. They focus on ramping up long‐acting PrEP as a key component of HIV prevention. As highlighted in the opinion piece by Jirair Ratevosian, PEPFAR has evolved far beyond its original “emergency plan,” becoming indispensable to global HIV prevention and treatment. Embracing these reforms, he writes, would ensure PEPFAR remains resilient and impactful amid rising infections, geopolitical strains, and domestic political uncertainty. 

READ:

• It’s Time for PEPFAR to Embrace Reform—Global Health Now 
• By executive order: The likely deadly consequences associated with a 90-day pause in PEPFAR funding—Journal of the International AIDS Society 

The Impact of Funding Cuts and Frozen Aid

Nearly two months into the dismantling of foreign aid and the research enterprise, the scale of the threat to vulnerable populations and global health is coming into sharper focus. New modeling data presented at CROI shows that nearly one in five children under one with HIV who experienced a treatment interruption in 2024 died, based on a review of over half a million children in US-funded PEPFAR programs. With major challenges to sustaining access to treatment since the new administration froze PEPFAR funds, the findings from this modeling study are a dire warning of the toll on lives to be expected from these policy changes. Meanwhile, clinical trials for new prevention tools, such as long-acting injectables and HIV vaccines, have been halted or scaled back, while organizations that built local research capacity and trust with communities now face staff layoffs and funding shortfalls.  

IMPLICATIONS: The loss of data from these canceled projects will undermine governments’ ability to sustain the HIV response, with or without U.S. support, and reduced investment in infectious disease research could drive up costs in the long run. 

READ:

• US funding cuts imperil search for HIV vaccine—Spotlight SA  
• PEPFAR study shows the deadly impact of stopping children’s HIV treatment—aidsmap  

Africa and Sustainable Health Funding 

Global health leaders are joining calls from civil society for African nations to break free from donor dependency by building self-sufficient, locally-driven health systems that prioritize their own needs and strategies. A rethinking of traditional aid models in favor of sustainable, equitable investments in health infrastructure and local research is needed and holding donor countries accountable for supporting true development rather than perpetuating reliance on external funding is imperative.  

READ:  

• After USAID: what now for aid and Africa?—BMJ  
• Africa’s defining moment: the time to lead the HIV response is now—Lancet Global Health

What We’re Reading

• Cuts to USAID-funded Research Another Blow to Global HIV Response—Devex
• US Funding Cuts Imperil Search for HIV Vaccine—Spotlight SA
• Opinion: Trump’s war on science imperils global development and cooperation—Devex
• Tuberculosis Resurgent as Trump Funding Cut Disrupts Treatment Globally—The New York Times
• Scoop: White House pulls CDC director nomination—Axios  

Resources

• Impact of US funding cuts on the global AIDS response—UNAIDS
• PEPFAR Watch
• Project 2025 Tracker
• Litigation Tracker—Just Security 
• Federal Government Outlays—DataETC

Many researchers and advocates are on their way home from San Francisco where the Conference on Retroviruses and Opportunistic Infections (CROI) just wrapped up. The science showcased the great promise and importance of research and made clear just how much is at stake. You can read more about the promise of scientific advances against the backdrop of the US government’s priorities here and here.

The science offered at the Conference on Retroviruses and Opportunistic Infections (CROI) 2025 is a showcase of the great promise and importance of research. With broadside attacks and a sweeping funding withdrawal by the US government affecting science and global health, these advances in the field make clear how much is at stake. Innovation in long-acting PrEP could transform global health, new evidence to support on-demand PrEP among women, insights coming from cure research, and expanding efforts to confront an epidemic in sexually transmitted infections (STI), if the field can unite behind the evidence and refuse to be defeated.  

New data presented Monday underscores these dire realities: nearly one in five children under one with HIV who experienced a treatment interruption in 2024 died, based on a review of over half a million children in US-funded PEPFAR programs. These findings emphasize the critical need to maintain uninterrupted care for young children with HIV, who are especially vulnerable to rapid disease progression, and starkly highlight the catastrophic risks associated with halting funding for treatment programs. 

Read on for more important scientific highlights. 

The Power of LEN for PrEP

A once-yearly injection of lenacapavir (LEN) for PrEP took a step forward. Renu Singh of Gilead Sciences presented data from an ongoing, open-label study of the pharmacokinetics (how a drug is absorbed, distributed and eliminated in the body at a given dose), safety and tolerability of two LEN injections testing an intramuscular formulation. Singh reported that drug concentrations were as good as or better than the 6-monthly subcutaneous dose that showed 100% efficacy in 2024.

“It gives me a great pleasure to see a small molecule last this long. It’s never been done before. Once yearly injectable LEN for PrEP has the potential to offer high efficacy.”

The doses were safe and well tolerated. A Phase 3 study is expected to launch later this year, with possible regulatory submissions in 2027. Gilead’s application for twice-yearly LEN for PrEP is currently under FDA priority review with a decision expected by June 19. (ViiV Healthcare is similarly advancing their four-month injectable cabotegravir (CAB) towards possible regulatory submission, while the two-month formulation is rolling out.) 

More data from the PURPOSE Trials were presented showing that a cohort of 16-17 year-old females were just as well protected by 6-month injections of LEN for PrEP as adults in the larger study. Katharine Gill of the Desmond Tutu HIV Foundation, South Africa credited the PURPOSE trials and Good Participatory Practice for the landmark study, the first large-scale trial to include adolescents in the initial study design. Despite having high HIV incidence, adolescents have historically been excluded from Phase III HIV trials, resulting in prolonged delays in access to PrEP.

“PURPOSE 1 shows us that working with community and including adolescent stakeholders, we can design ethical studies that are effective and inclusive, especially for young women who need prevention the most,” said Gill.

On Demand PrEP for Cis-gender Women: 3 days or 4?

Findings from a modeling study explored how to optimize an on-demand protocol for HIV protection in the female genital tract. On-demand PrEP, sometimes called event-driven PrEP or 2-1-1, is a CDC approved protocol for men who have sex men who opt to take PrEP over a three-day period, starting 2-24 hours before the time of a specific sexual exposure, then 1 pill every 24 hours for the following two days. Mackenzie Cottrell of the University of North Carolina reported findings that adding a fourth day of dosing heightened protection from vaginal exposure to HIV.  

Dosing of 2-1-1-1 showed 84% protection, 2-2-2-2 showed 95% protection. Cottrell said, “While limited data suggest 2-2-2-2 dosing is safe for short-term use, the 2-1-1-1 regimen may better balance safety, efficacy, and tolerability while maintaining effectiveness” Cottrell recommended the 2-2-2, 2-1-1-1, and 2-2-1-1 regimens be considered in future clinical studies of on-demand PrEP in cisgender women. 

This data builds on the analysis of a body of evidence, led by Jeanne Marrazzo, now director of NIAID, showing that oral PrEP can reliably prevent HIV infection in cisgender women even with non-perfect adherence.

MK-8527: A Monthly PrEP Pill 

Merck presented an analysis of animal and Phase I data that informed the MK-8527 doses chosen to be tested in its ongoing Phase II PrEP trial. Looking at protection provided in monkeys, as well as pharmacokinetic data in humans, Merck determined that a monthly dose of at least 6 mg would provide adequate protection in more than 90% of the population intended for MK-8527 use. The Phase II trial is testing 3mg, 6mg, and 12mg doses in participants with low risk of HIV exposure. Watch this space for further information about how the Phase II trial will inform the upcoming efficacy program of MK-8527 expected to start later this year.

F/TAF Works in Women With Med-High Adherence 

Flavia Kiweewa of Makerere University-Johns Hopkins University Research Centre in Uganda presented important new prevention evidence from the PURPOSE 1 trial that tested both injectable LEN and F/TAF among cisgender women for PrEP. This new analysis found the chance of acquiring HIV was 89% lower when adherence to F/TAF reached two pills per week or more.  

Kiweewa reported that “nearly all incident HIV cases in participants receiving F/TAF in PURPOSE 1 were attributable to low oral PrEP adherence… taken together, these results suggest that HIV infections in PURPOSE 1 occurred almost always in the context of nonadherence to F/TAF, with rare emergence of HIV resistance and low risk of HIV diagnosis delay.” Kiweewa concluded that F/TAF is another prevention tool that should be considered for women who prefer a daily oral HIV prevention option.

Advances in Cure Research

A key focus for cure research at this year’s CROI was data from the FRESH Cohort in South Africa looking at delivery of the CAP 256 broadly neutralizing antibody (bNAb) in combination with TLR9, an immune activator developed by Gilead Sciences, to women identified and treated extremely early in infection. The trial involved an analytical treatment interruption (ATI) and allowed for eight weeks of consecutive viral loads above 1,000 copies before treatment was restarted. This allowed the researchers to see interesting viral dynamics, including about a third of the women experiencing multiple periods of viremia off therapy, some even getting close to 100,000 copies/mL in blood. The viral loads quickly returned to undetectable (after re-starting therapy?). Four women in the trial continue to remain off therapy.  

Investigators from another key cure study, the RIO study, shared results that bNAbs at the time of treatment initiation were able to achieve durable control. Twenty-one individuals had delayed rebound with seven experiencing rebound over one year. The numbers are small, but combined with other basic and clinical trial data, bNAbs are an intervention to watch—for possible prevention, treatment and cure! 

The Latest on DoxyPEP

While doxyPEP is already in use as an STI prevention intervention in several countries, ongoing research continues to address key questions regarding antimicrobial resistance, adherence, and identifying the populations that would benefit most. The PRIDOX study looked at the impact of doxyPEP in “high-risk MSM” who were also using PrEP in a real-world setting. Christina Gómez-Ayerbe presented data showing that the 197 study participants who started doxyPEP saw lower incidence of syphilis, gonorrhea and chlamydia at the end of the study than the incidence rates at the beginning of the study before starting doxyPEP. And similar to most doxyPEP studies, there were higher rates of gonorrhea than the other bacterial STIs studied. Even among participants who contracted gonorrhea while on doxyPEP, no cases of drug-resistant strains or other forms of microbial resistance were observed—a notable finding given that some other studies have reported modest increases in AMR among doxyPEP users. 

Another study from Milan, Italy, looked at doxyPEP use among MSM using the U.S. CDC’s doxyPEP guidelines (which suggest prescribing doxyPEP for MSM and transgender women who have had one STI in the past 12 months). It found that out of 251 participants, 85 infections could have been prevented with doxyPEP, yet 164 individuals would have been unnecessarily prescribed it since they had no further STIs. Dr. Roberto Rossotti suggested the CDC guidelines might be too broad and should instead consider condomless sex acts as the prescribing criterion. Download AVAC’s Advocacte’s Guide to Doxycycline to Prevent Bacterial STIs.

HPV Vaccination and Global Inequities

Namwa Wongkalasin of Imperial College delivered an impressive presentation on the potential of HPV vaccination to prevent non-cervical cancers (i.e., oral and anal cancers), while highlighting the grave challenge of global inequities in vaccine access and coverage—particularly in regions that would benefit most. “Due to unprecedented cuts in global aid funding, this disparity will increase further,” she warned. We are likely to see these effects immediately amid troubling developments at NIH, where grants focused on studying vaccine hesitancy, acceptance, and uptake—particularly those examining HPV and gonorrhea vaccine attitudes—have been terminated. These NIH-funded studies have been pivotal in shaping strategies to boost HPV vaccination rates. 

Community Breakfast Club Sessions

Catch up on our CROI 2025 Community Breakfast Club recordings! These virtual sessions, hosted by the CROI Community Liaison Subcommittee, the European AIDS Treatment Group, AVAC, and partners featured researchers and advocates discussing cutting-edge advances in HIV cure, reflections on 40 years of the epidemic, and insights on living long-term with HIV. Watch the recordings now!

And be sure to check out Aidsmap’s news bulletins and in-depth coverage of CROI. 

Scientists and advocates will undoubtedly continue to be confronted with the new administration’s assaults on scientific integrity. Read more about how these attacks are expected to devastate HIV prevention, including the capacity to deliver existing PrEP options, scale up new PrEP products, and paralyze the impact of innovative and exciting research like we’ve just heard this week in our special issue of PxWire.

Defeating HIV has demanded heroics since the first report of a deadly new syndrome in the 1981 Morbidity and Mortality Weekly Report of the Centers for Disease Control. People devastated by AIDS, advocates putting their lives on the line to demand care, doctors and researchers struggling to find options—all facing down a plague that meant certain death.  

Those gathered at the Conference on Retroviruses and Opportunistic Infections (CROI) 2025, which is ongoing in San Francisco through March 12, are taking stock of a grim new reality that will once again demand heroics of us all. Today the science is on our side with better solutions than ever before to control the epidemic (stay tuned for a roundup of the science). But the HIV response, from basic science research to community service providers, is now practically paralyzed by a despotic U.S. government, newly in power, that is attacking every aspect of scientific enterprise, global health, and foreign aid. Voices across sessions at CROI joined in calling for courage and solidarity.  

Rebecca Denison, found of WORLD and a 42-year HIV survivor, opened the conference (slides here) with a stark assessment of the policies of the new US Administration as “going beyond persecution” and demanded action from us all.

“Silence ensures the abuse of power will continue… Now is the time for moral courage.”

Denison said too few Americans understand the dividends HIV research and development has paid out to them over the decades, accelerating technology from testing to vaccines. Communicating the impact and value of these historic investments is essential.

“Many Americans don’t know that the world waited four years for a test for HIV, which made possible the development of a COVID test in a matter of weeks.”

Chris Beyrer of Duke Global Health Institute at the Monday plenary address (slides here) put a spotlight on the historic achievements of U.S. President’s Emergency Plan for AIDS Relief (PEPFAR), now in jeopardy. Before PEPFAR, Gross Domestic Product (GDP) and life expectancy were in decline. After 20 years of PEPFAR investment, GDP is on the rise, 25 million lives have been saved and 5.5 million at-risk babies were born HIV free. It took diversity, inclusion and equity to achieve these results.

The staggering impact of withdrawing PEPFAR supported programs has been recently estimated in a JIAS publication: “Each day of the funding freeze about 220,000 including over 7000 children, will be unable to access their needed treatment.” For the latest on the foreign aid freeze and the AVAC vs, Department of State lawsuit, visit our frequently updated webpage.  

Beyrer called for restoring PEPFAR, sustained support for community partners especially those serving key populations, restoring the functions of the National Institutes of Health, the Centers for Disease Control and Prevention, and the US Food and Drug Administration, and for safeguarding human rights.

At Tuesday’s Community Breakfast Club, where advocates met with CROI researchers, Chilufya Kasanda Hampongo of TALC in Zambia said advocacy must be unswerving in protecting the gains in HIV prevention. “We got here, as Rebecca Denison reminded us, by building coalitions, using our voices, and demanding inclusive dialogues. We cannot abandon equity, inclusion and diversity.” 

The calls for researchers to be in solidarity with advocates and communities that benefit from their research spilled out of the Mascone Center and into the streets of San Francisco on Monday as well. Several researchers and activists addressed a crowd of hundreds at the Save Our Sciences Rally to Protect HIV Research. The rally, organized by the San Francisco AIDS Foundation demanded restoration of cuts to research and implementation programs that have been gutted at USAID, PEPFAR and NIH. Speakers called for the kinds of activism necessary to create the infrastructure for HIV research and programs, as well as the impact that HIV researchers have had on other issues, including vaccines and therapies now widely used to treat, cure or prevent Hepatitis B & C, COVID-19 and other disease areas. 

The latest science presented at CROI represents a stunning achievement, built on 40 years of advocacy, coalition, toil and discovery. As we wrote in a recent newsletter, “These are immensely challenging times for all of us, and it is easy to be paralyzed, overwhelmed and depressed. But we’ve all come too far for that to be the new normal. Lives, economies and democracies depend on our collective ability to stand up and fight back.” 

Stay tuned for our round up of HIV prevention research and development at CROI including exciting new data on a one-year injection of LEN for PrEP, on-demand PrEP protocols for women, LEN for PrEP among adolescents, a monthly oral PrEP pill, the impact of DoxyPEP, the latest on cure, and so much more.  

This week, the 32nd annual Conference on Retroviruses and Opportunistic Infections (CROI) kicks off, running March 9–12 in San Francisco, CA. CROI opens under drastically altered circumstances, as the new US Administration’s assault on global health and research devastates the HIV response. Foreign aid programs are frozen, US agencies championing science and global health are being dismantled, and US leadership around the world is receding at a critical moment.

Despite these challenges, scientists and advocates will come together—though many from pivotal US health agencies will be missing—to confront the impact and implications of these changes and join in solidarity to strategize a future for public health, help advance research and ensure that hard-won progress in HIV is not lost. 

Whether attending in person or not, this email shares ways to follow along and join in the discussion and debate.

New Issue of PxWire

This issue released just ahead of CROI dives into the devastating impact of the new US administration on HIV prevention—from crippling existing PrEP delivery to threatening the rollout of LEN for PrEP and paralyzing R&D.

Read the issue!

Follow Along

In the midst of it all, we’re tracking several promising PrEP developments including new data on the investigational monthly oral PrEP pill, MK-8527; data from lenacapavir for PrEP’s PURPOSE 1 study on preferences for injectable versus oral PrEP; the dapvirine vaginal ring (DVR) in pregnancy; doxycycline as post-exposure prophylaxis (DoxyPEP) to prevent sexually transmitted infections (STIs); the latest in HIV cure and control; and more. 

Be part of the conversation by following AVAC on BlueSky at @hivpxresearch.bsky.social, and be sure to sign up and follow our partner, Aidsmap, which we’re delighted to know is back in action and reporting from the conference.

Community Breakfast Clubs

Join the CROI Community Liaisons, AVAC, the European AIDS Treatment Group, and partners for daily Community Breakfast Clubs. These live webinars feature researchers and advocates exploring some of the most consequential science and discussions from CROI. They are open to all; CROI registration not required.  

Monday, March 10, 7:00am – 8:00am PT 
Breaking New Ground: The latest advances in HIV Cure
 
Tuesday, March 11, 7:00am – 8:00am PT
The End of AIDS- Near and Far? (40 Years of HIV)
 
Wednesday, March 12, 7:00am – 8:00am PT
Still Here! Living with HIV Long-term (treatment, aging, and co-morbidities)

Click here to determine the time in your location.

Sessions of Interest