For twenty years, PEPFAR has been the backbone of the global HIV response. In 2025, that backbone absorbed a cascade of shocks at once: the program’s statutory authorization expired; foreign assistance was frozen; stop-work orders hit ongoing awards; and an attempted rescission package triggered courtroom and congressional pushback. These events-sometimes reversed at the eleventh hour by federal rulings-produced real service disruptions in some high-burden countries while scrambling partners’ visibility on the funding trajectory. Paradoxically, a formidable prevention opportunity is emerging at the same time: long-acting pre-exposure prophylaxis (PrEP) with lenacapavir, administered twice per year, which the United States intends to deploy at cost to as many as two million people by 2028 in partnership with the Global Fund. This collision of a governance crisis with a breakthrough technology imposes a dual imperative: secure continuity of care and reboot prevention at speed; otherwise the technology window will close without lasting impact.

What changed in 2025 - and why it matters

The turning point in 2025 began with the expiration of PEPFAR’s authorization on March 25. Legally, the program can continue under permanent authorities provided Congress appropriates funds, but several time-bound provisions-governance guardrails, set‑asides, and parameters guiding U.S. multilateral engagement-lapsed, injecting ambiguity into agency operations and partner coordination. On top of the lapse came freezes, stop‑work orders, and rescission attempts that disorganized project delivery for weeks. A federal judge ultimately ordered the release of $11.5 billion in withheld foreign assistance, reaffirming congressional control over public spending. Far from a procedural footnote, this translated into operational whiplash for beneficiaries. At IAS 2025 in Kigali, the International AIDS Society welcomed a bipartisan Senate move to shield PEPFAR from a proposed $400 million cut in the rescission package-an important political win that confirmed the program still commands cross‑party recognition. Yet it also exposed the fragility of an architecture increasingly dependent on last‑minute rescues. The shock rippled across the Global Fund ecosystem as well. The lapse of several time‑bound provisions that had effectively framed U.S. contributions (caps, conditions, timing) created legal and political gray zones. In a tight budget cycle, ambiguity alone can delay disbursements, blur replenishment signals, and complicate synchronization with country grant calendars. Data governance came under strain too: compressed planning “sprints” and delays relative to PEPFAR’s historical cadence of public reporting weakened real‑time course correction. A data‑driven program cannot afford thinner dashboards; time‑bound commitments to publish continuity indicators (TX_CURR, viral load suppression, PrEP initiation and continuation by age band and key population, missed‑visit rates) with district‑level disaggregates are essential, alongside institutionalized monthly triangulation via community‑led monitoring.

Country impacts and near‑term risks

On the ground, consequences were precisely documented in Tanzania and Uganda. A Physicians for Human Rights field study shows that the aid freeze and partial waivers, in some settings, disrupted antiretroviral dispensing, narrowed prevention-especially for key populations-triggered layoffs, and eroded community trust in service continuity. In certain phases, PrEP access was limited to pregnant and breastfeeding women even as incidence remained high in groups excluded from those waivers. Differentiated service delivery models-multi‑month dispensing, community distribution, decentralized pick‑up points-were interrupted without notice, creating risks of treatment lapses and prevention gaps. Across sub‑Saharan Africa, observed slowdowns overlap with high‑burden geographies where clinic closures, staffing gaps, and suspended prevention create epidemiologic blind spots. Three near‑term priorities dominate: securing treatment continuity (90–180‑day dispensing, community pick‑up points, emergency refills); relaunching prevention for key populations and adolescent girls and young women (restart oral PrEP and quickly pilot lenacapavir in high‑incidence districts); and repairing last‑mile supply chains where USAID‑funded systems were shaken. Experience from Tanzania and Uganda indicates these measures are feasible with targeted financing and rapid legal clarity.

Figure 1. Qualitative program risk by scenario (illustrative).

Long‑acting PrEP: promise, prerequisites, and equity

This is where lenacapavir-twice‑yearly long‑acting PrEP-enters. The United States has announced an at‑cost access pathway through PEPFAR, in partnership with the Global Fund, aiming for up to two million people by 2028, with agreements already underway in a dozen countries. The semiannual cadence can sidestep adherence barriers of daily PrEP, offering an equity‑enhancing prevention option if deployed with community demand creation and adolescent‑friendly services. Impact, however, depends on meticulous implementation: clear regulatory status, HIV‑testing algorithms aligned to the product’s pharmacology, appointment reminder systems, missed‑dose protocols, robust pharmacovigilance, and back‑up oral cover to mitigate resistance risk. Without this operational discipline, the innovation risks becoming a mirage rather than a turning point.

Figure 2. Continuity pillars to protect (importance weighting, illustrative).

4) Scenarios, priorities, and the path forward

The next 6–12 months could follow three plausible trajectories. In a partial stabilization scenario, courts continue to constrain attempts to withhold appropriated funds, appropriations stay near level, and waivers broaden to cover a wider prevention package-yielding uneven but improving service recovery and pilot roll‑out of long‑acting PrEP. Under rolling uncertainty, appropriations remain but planning stays compressed, public data lag, and some multilateral contributions are delayed; subnational programs operate month‑to‑month, with community cadre attrition and persistent prevention gaps. Under deep cuts with slow relief, larger FY2026 reductions materialize, injunctions narrow, and multilateral buffers prove slow to arrive: treatment is maintained at bare minimum while prevention collapses in multiple hotspots and incidence rises. A pragmatic playbook for PRs, CCMs, and ministries follows from these scenarios: protect the clinical spine; restore prevention at speed; govern with data under uncertainty; finance buffers and legal clarity; and coordinate with the Global Fund to plug prevention and last‑mile logistics gaps while maintaining complementarity. The advocacy agenda is equally clear: reauthorize PEPFAR with restored guardrails; enforce timely data transparency with key‑population disaggregates; protect multilateral contributions by clarifying Global Fund timelines; mobilize non‑U.S. bridge financing against FY2026 cliffs; and accelerate WHO/national regulatory pathways and pharmacovigilance for safe lenacapavir scale‑up. Ultimately, the opportunity in this crisis is the operational discipline it demands. If programs protect care continuity and reboot prevention rapidly and well, long‑acting PrEP can bend the curve where daily PrEP faltered-especially for adolescent girls and young women and key populations. Without reliable financing, radical transparency, and community partnership, innovation will remain theoretical and a rare prevention window will close.

Table 1. Three plausible scenarios and monitoring priorities.

Table 2. A pragmatic playbook for PRs, CCMs, and ministries.

Note: Figures are conceptual and illustrative for planning purposes; they are not empirical estimates.