The HIV/AIDS pandemic: where are we now?

Abstract

The global HIV/AIDS response is facing its most serious crisis in decades. Despite expanded access to antiretroviral therapy (ART) and the growing availability of prevention tools such as oral preexposure prophylaxis (PrEP), and long-acting PrEP, progress toward the UNAIDS 2025 targets has stalled. HIV incidence remains unacceptably high across key populations and geographic regions, while treatment coverage gaps and preventable deaths persist. The abrupt 2025 suspension of U.S. foreign aid programs, including the President's Emergency Plan for AIDS Relief (PEPFAR) and the United States Agency for International Development (USAID), has further disrupted service delivery, particularly for prevention programs and marginalized groups. This editorial assesses the underlying structural, political, and programmatic failures that led to missed targets and highlights the compounded risks posed by policy reversals. Drawing on recent epidemiological data and modeling, we estimate the impact of prevention gaps, disparities in access, and policy changes on global HIV trajectories. We argue that a path forward requires reforms, renewed political will, and sustainable financing. In a moment of rising global polarization and shrinking public health budgets, the HIV response must be reimagined around equity, inclusion, and collective action. Without such recalibration, the vision of ending AIDS as a public health threat by 2030 will remain out of reach.

Introduction

The global HIV/AIDS response faces its most significant challenge since the early days of the epidemic more than 40 years ago. Although tremendous progress has been made in treatment and prevention – especially in the last two decades – the ambitious targets set by UNAIDS for reductions in new infections, increases in treatment coverage and reductions in AIDS deaths by 2025 remain unmet, and are changing too slowly to achieve epidemic control. These realities were the case before the drastic decreases in spending and programs implemented by the new U.S. administration beginning on January 20, 2025 [1]. A pause on PEPFAR programming, and the gutting of USAID have meant that the very programs that have saved millions of lives now face existential threats [2]. The current global landscape for HIV/AIDS prevention, treatment, and care faces new levels of uncertainty which could reverse decades of progress.

This editorial examines how the global response was off track in 2024, analyzes the systemic challenges preventing achievement of the 2025 goals, including ongoing incidence and the challenges of primary prevention with our current tools, and addresses the shock delivered to global AIDS programs by the January 2025 pause on PEPFAR funding. Drawing on evidence from recent HIV prevention and HIV vaccine trials and epidemiological data, we demonstrate that HIV incidence remains stubbornly high even as treatment coverage has expanded. Further, we demonstrate that significant increases in primary prevention programs will be required to achieve epidemic control. We believe that we now have the prevention and treatment tools to achieve UNAIDS targets; what we need are resources and political will.

The January 2025 Executive Order suspending foreign aid programs, including PEPFAR, has created unprecedented disruptions in HIV treatment and prevention services, leaving millions at risk as clinics close and programs shut down [3]. While a February waiver restored some essential services, most prevention programs remain paused, and PrEP supported by PEPFAR is currently only available to pregnant and breastfeeding women. Key populations, who face the highest incidence rates across all regions, have been excluded “until further notice” from all prevention programming, including PrEP, and have also been erased from data collection and monitoring frameworks, making it all but impossible to understand what is happening to these populations as programs shut down. Available data up through 2023 showed that key populations and their partners account for more than half of all new infections globally [4], making this loss of data and programs of profound impact for the global response.

We argue that the AIDS response must evolve to address these challenges by embracing necessary reforms while preserving core values of diversity, equity, and inclusion. Various reform proposals from Duke Global Health Institute [5] and other organizations offer pathways for PEPFAR to become more sustainable and country-led without abandoning its life-saving mission. Rejecting the false choice between prevention and treatment in resource-constrained environments, we call for expanded partnerships, innovative financing mechanisms, and renewed political commitment to put the response (back) on track to deliver both prevention and treatment at scale as an effective way to curb the epidemic. Congress must authorize PEPFAR for at least five years, providing stability for implementation of essential reforms while maintaining services for those who depend on them. The path to 2030 and beyond requires collective action and moral clarity to realize the vision of ending AIDS as a public health threat.

Global response was – and is – off track

In 2014, UNAIDS introduced the 90–90–90 targets as a global framework to end the AIDS epidemic by 2030. The focus on reaching the ‘first 90’ in the 90–90–90 targets (90% diagnosed, 90% on treatment, 90% virally suppressed) to be reached by 2020 lost urgency in many regions as attention shifted to other global crises. Building on that momentum, the 95–95–95 goals were introduced one year later to accelerate gains and close remaining gaps.

The global HIV response entered 2025 already significantly off course. Despite enormous strides since the early 2000s, when life expectancy declined across sub-Saharan Africa and 29 million people lacked access to treatment, the momentum has faltered. The global AIDS response failed to meet key UNAIDS 2025 targets in two crucial areas: treatment coverage and declines in incidence. Treatment coverage fell short of the goals, with 10 million people – 25% of the 40 million people living with HIV worldwide--not receiving life-saving antiretroviral therapy (ART) [6]. Despite falling short, 20 of the 30 million people accessing treatment were supported by PEPFAR and the Global Fund, a historic achievement [7].

As a consequence of the treatment gap, AIDS-related mortality continues to decline too slowly. Late diagnosis and advanced HIV disease persist as major contributors to preventable deaths. Some countries and regions have attained or are close to the 95–95–95 goals but are now at risk of losing the progress that was made [8].

Second, and most concerning, HIV incidence remains stubbornly high. The prevention gap must be closed to lessen the ever-expanding need for treatment. The data from placebo arms of recent prevention trials present a sobering reality check: incidence rates hover around 4 per 100 person-years among women in sub-Saharan Africa and among men who have sex with men globally and show negligible evidence of decline over time. Even in HIV vaccine efficacy trials where participants had access to oral preexposure prophylaxis (PrEP), such as the recent Mosaico trial among MSM and transgender women, incidence remained stubbornly high, particularly in Latin America, where most trial participants were recruited [9].

Three regions – Eastern Europe and Central Asia, Latin America, and the Middle East and North Africa – continued to experience rising HIV incidence through the end of 2024, further challenging the ability to control the pandemic [10].

The global burden of disease study paints a sobering picture for the next twenty-five years [11]. HIV prevalence continues to rise and, under even optimistic scenarios that assume stable funding and programming (assumptions now invalidated by recent developments), prevalence would not begin to level off until 2050. Even in the most optimistic scenario, tens of millions of persons would need to be maintained on ARV for decades to come, adding urgency to the search for a functional cure for HIV infection.

The challenges extend beyond epidemiological trends. While 2024 witnessed substantial progress in PrEP rollout globally, with over 90% of new starts attributable [12] to PEPFAR, the prevention gains lag significantly behind new infections. HIV acquisitions are outpacing PrEP. In Eastern and Southern Africa alone, 8.8 million new HIV infections occurred from 2012 (when oral PrEP was first approved) through 2023, compared to 6.4 million PrEP starts – meaning for every person started on PrEP, approximately 1.5 new infections occurred. Even in the regions performing better than the global average, such as Eastern and Southern Africa (largely due to PEPFAR) and high-income countries in Western and Central Europe and North America, prevention scale-up is not keeping pace with the epidemic (Fig. 1).

Fig. 1.

Cumulative change in people on ART, cumulative HIV acquisitions and cumulative PrEP initiations since oral PrEP was approved in 2012.

Globally, since oral PrEP was first approved in 2012, the number of people acquiring HIV has outpaced the number of people starting PrEP by more than 2 to 1 – showing that PrEP uptake is too low to effectively prevent new infections. In Eastern and Southern Africa, the number of people acquiring HIV has outpaced the number of people starting PrEP by ∼1.5 to 1 – showing that PrEP uptake is also too low to effectively prevent new infections, but better than the global average, 90% of these PrEP starts were paid for by PEPFAR. In Eastern Europe and Central Asia, the number of people acquiring HIV has outpaced the number of people starting PrEP by ∼42 to 1 – showing that PrEP uptake is far too low to effectively prevent new infections.

In regions like Eastern Europe and Central Asia, the situation appears even more dire, with minimal PrEP implementation despite high rates of new infections. This regional disparity highlights how political barriers, stigma, and discrimination continue to obstruct effective responses, particularly for key populations and in political environments hostile to prevention, such as the Russian Federation.

Why we did not meet 2025 goals

Multiple intersecting factors contributed to our collective failure to meet the 2025 goals.

First, the prevention paradox has intensified. As the overall incidence of HIV decreases in many settings, the number needed to treat with PrEP to prevent a single infection increases significantly. In populations with incidence of 3 per 100 person-years, approximately 33 people must receive PrEP to prevent one infection, but in populations with incidence <0.5 per 100 person-years, more than 200 people must receive PrEP to prevent one infection (Fig. 2a and b). This creates an implementation challenge: targeting only the highest-risk populations improves efficiency but has minimal impact on the overall epidemic (Fig/ 2a and 2b, Scenario I), while broader implementation could avert 90–95% of new infections but would require placing tens of million people on PrEP (Fig. 2a and b, Scenario IV) [13].

Fig. 2.

Data come from national surveys conducted from 2015 to 2019 representing 118 million women aged 15–49 (a) and 122 million men aged 15–59 (b).

In LASSO statistical models, only two variables were needed for high prediction: living in an area with high population viremia (both models), reporting a sex partner outside the home (female model), and reporting sex with men (MSM) (male model). Four scenarios (I–IV) along the modeled ROC curve are depicted. Scenario I represents low reach, excellent efficiency, and few cases averted. Scenario IV represents high reach, moderate efficiency, and nearly all cases averted. The results can guide policy-makers’ choices based on different prevention goals (cases averted), resource levels (reach), and efficiency needs. (a) Policy tradeoffs between PrEP reach and efficiency among women in 15 countries. (b) Policy tradeoffs between PrEP reach and efficiency among men in 13 countries.

Second, stark disparities in access to prevention and treatment services persist along lines of race, gender identity, and key population status. The widening gap in HIV incidence between White and Black gay and bisexual men in the United States exemplifies this problem [14]. Despite major biomedical advances – treatment as prevention (U=U), PrEP approval, and home HIV test kits – incidence among Black men has remained staggeringly high while declining steadily among White men.¹⁴ Similar access disparities exist for transgender women, people who inject drugs, and sex workers globally.

Third, the integration of HIV services with broader health systems remains incomplete, despite calls for integration and progress in recent years [15]. While treatment programs achieved remarkable scale, prevention services often remained siloed, under-resourced, and disconnected from other health priorities. Findings from the SEARCH study in Kenya and Uganda similarly underscore the value of integrated, person-centered care, showing that combining HIV services with broader health interventions – like hypertension and diabetes screening – increased engagement and improved outcomes across multiple conditions [16]. The data from the LIGHT cohort of transgender women in the United States illustrates the potential of integration: viral suppression rates improve dramatically when HIV care is combined with gender-affirming care through exogenous estrogen therapy [17].

Finally, we have failed to adequately address the social and structural drivers of HIV risk. Criminalization of key populations, gender inequality, economic marginalization, and human rights violations continue to undermine even the most well designed biomedical interventions [18]. The prevention toolbox has expanded impressively, but the tools to dismantle structural barriers remain underutilized [19,20].

2025 shocked global HIV/AIDS programs

The most severe shock to global HIV/AIDS programs came in early 2025 with the abrupt pause on PEPFAR, USAID, and the President's Malaria Initiative. After two decades of bipartisan support and remarkable achievements – 25 million lives saved, 20 million more people on treatment, 5 million infants born HIV-free – PEPFAR faced an unprecedented crisis. According to our estimate, the proposed 90-day policy review by the new administration may result in over 100 000 preventable deaths within a year and over 135 000 perinatal transmissions [21].

The impact has been swift and devastating. While a limited waiver from the Department of State on February 6, 2025, attempted to mitigate the damage by continuing support for “life-saving HIV treatment, care and prevention and PMTCT,” it explicitly restricted PrEP to pregnant and breastfeeding women and those “previously initiated.”

Most concerning, it removed key population disaggregates from monitoring and evaluation frameworks, effectively erasing men who have sex with men, sex workers, people who inject drugs, transgender people, and prisoners from the data. Modeling studies have projected severe consequences of these policy changes. For sex workers in Eswatini, for example, even brief interruptions in services increase HIV incidence. In worst-case scenarios where targeted services are eliminated entirely, spikes in new infections occur rapidly [22].

Removing PEPFAR-funded PrEP for key populations (KPs) in sub-Saharan Africa could lead to a sharp increase in new HIV infections, particularly in countries with higher coverage levels. When PrEP coverage among KPs exceeds 10%, the absence of this support could result in over a 30% rise in new infections among female sex workers (FSW), approximately 20% among men who have sex with men (MSM) and transgender women (TGW), and around 15% among people who inject drugs (PWID) [23]. These projections underscore the critical role PEPFAR plays in sustaining prevention gains and the disproportionate impact any funding cuts could have on vulnerable communities [24].

Human Rights Watch has documented that the limited waivers have failed to restore vital programs, as millions have paused treatment or remain at risk for infection due to shutdowns [25]. The impact extends beyond PEPFAR itself. Since 60% of PEPFAR funding has historically been implemented through USAID, with an additional 37% through HHS (primarily CDC), disruptions to these agencies have severely compromised implementation capacity [26]. And even when programs are reinstated on paper, the damage to trust – especially in fragile settings – is deep and not easily repaired, risking efforts to prioritize sustainability and long-term co-financing planning.

The Trump administration's intent to extinguish USAID – an agency that received 60% of the US$4.76 billion distributed by PEPFAR in fiscal year 2022 – has added to PEPFAR's current and future instability. The effects ripple across maternal and child health, family planning, tuberculosis, malaria, and global health security programs, all heavily dependent on USAID infrastructure. With the PEPFAR and USAID scaffolding suddenly withdrawn these collateral benefits turn into collateral damage, and approved programs simply cannot be implemented.

The situation has been further complicated by leadership changes at the Department of Health and Human Services. New policies explicitly targeting gender-affirming care as “gender ideology” threaten to undermine evidence-based approaches to reaching and serving transgender populations, a group already experiencing disproportionate HIV burden.

The complexity of executive orders, pauses, and judicial decisions has created an atmosphere of chaos and uncertainty for implementers, researchers, and most importantly, for people living with and at risk for HIV. Perhaps most alarmingly, PEPFAR authorization expired on March 25, 2025, creating an urgent need for reauthorization to prevent further deterioration of programs and reinsert congressional oversight. Without reauthorization, those in the most fragile health systems and marginalized communities will be hit hardest – especially as the expiration of earmarks gives the administration broad discretion to delay, redirect, or reclaim PEPFAR funds, setting up a high-stakes clash with Congress over spending oversight.

How the HIV/AIDS response must change

The current crisis demands more than PEPFAR's reauthorization and incremental adjustments – it requires a fundamental reimagining of the global HIV response. The core values that have guided the response since its inception – diversity, equity, and inclusion – must be reaffirmed and strengthened, not abandoned.

First, we must close the treatment and prevention gaps. To reach the 95–95–95 goals, the number of people who are aware that they are living with HIV must increase by another 4 million to ∼38 million, of which ∼37 million should be on ART, of which ∼36 million would have undetectable HIV RNA. Prevention programs must be reinstated and further scaled up and diversified. The data clearly indicate that the combination of treatment at scale and prevention at scale are essential to achieve epidemic control. Advances in prevention technology, particularly long-acting injectables, offer new opportunities to reduce incidence, but they must be implemented at scale in both high and lower incidence populations. Conservative estimates suggest that more than 40 million people – exceeding the number currently on ART – will need to access PrEP to reach epidemic control.¹³

Second, we must prioritize equity and address disparities. The widening gaps in HIV outcomes along lines of race, gender identity, and key population status demand targeted, culturally competent, and rights-based approaches. The integration of HIV services with other health priorities, as demonstrated by the improved viral suppression among transgender women receiving gender-affirming care, offers a model for addressing the whole-person needs of marginalized communities.

Third, a new global coalition must emerge to close the gaps created by the current policy disruptions. Governments, the private sector, foundations, and communities will need to step forward with increased commitments. The upcoming Global Fund replenishment represents a critical opportunity to sustain and expand programs, particularly for key populations who have lost access to PEPFAR-supported services.

Fourth, we must embrace and implement necessary reforms to programs like PEPFAR while preserving their core life-saving functions. The rapid dismantling of programs is not a model of efficiency and will only lead to HIV resurgence. A recent policy brief from the Duke Global Health Institute outlines a comprehensive approach to “Reform and Renewal” for PEPFAR over the next 5 years [27]. The recommendations focus on several key themes: optimizing operations to reduce administrative costs, implementing graduated country financing to promote sustainability, strategically expanding to regions with rising infection rates, prioritizing prevention innovations, and leveraging digital technologies and private sector partnerships.

Now is the time for Congress to embrace these reform efforts by authorizing PEPFAR for at least five years, providing the stability and mandate needed to implement meaningful changes while maintaining life-saving services for the 20 million people living with HIV (50% of all people living with HIV) whose treatment is supported by PEPFAR.

Fifth, we must leave no one behind. We must stand in solidarity with all affected populations and uphold human rights as nonnegotiable principles of the HIV response. The removal of key population data from monitoring frameworks represents a dangerous precedent that must be reversed. Without disaggregated data, we cannot identify or address disparities, and marginalized communities become invisible in policy and programming decisions.

Getting to 2030 and beyond

As the UNAIDS Target Setting Task Force prepares to release new targets for 2030, the global community faces perhaps the most difficult period in the history of the HIV response. At a moment when discrimination is being promoted as a virtue, we are entering an era of unprecedented fiscal constraints across the globe. Governments worldwide are feeling intense economic pressure, domestic health resources are being cut, and U.S. foreign aid faces significant reductions. The global economic environment threatens to unravel two decades of progress in global health.

Global HIV treatment and prevention programs such as PEPFAR are not a zero-sum game. The progress we’ve made against HIV has always depended on a comprehensive approach that includes both prevention and treatment. Creating an artificial competition between these complementary strategies undermines the fundamental public health principle that prevention reduces the need for treatment, and that treatment for HIV is prevention.

Instead, we should focus on expanding the resource pie rather than fighting over its pieces. In an era of political shifts and competing health priorities, the HIV response must remain resilient and adaptable. Global health initiatives must make the case for HIV's continued prioritization, ensuring that it remains integral to health systems strengthening worldwide. This means working collaboratively across sectors – governments, multilateral institutions, private sector, philanthropic organizations, and affected communities – to raise additional resources and support an evidence-based response that will put us back on track.

Even in this constrained fiscal environment, smart investments in both prevention and treatment will yield dividends. Long-acting prevention technologies like injectable cabotegravir and lenacapavir offer the potential for more cost-effective prevention. Enhanced data systems, including AI-powered analytics, can help target resources to the geographic areas and populations with the greatest need. Community-led service delivery models can extend the reach of limited resources while strengthening local capacity.

The private sector, which has been an important but underutilized partner in the HIV response, must be engaged more intentionally. Public-private partnerships can leverage additional resources, drive innovation in service delivery, and create sustainable financing mechanisms that complement traditional donor funding.

At the same time, we must advocate forcefully for the continued political prioritization of HIV within broader global health and development agendas. This means demonstrating the return on investment of HIV programming, highlighting the cross-sectoral benefits of strong HIV programs to health systems more broadly, and building allies across the development spectrum.

The path forward will require difficult decisions, but the fundamental choice before us is not which aspect of the HIV response to sacrifice. Rather, it is whether we have the collective will and imagination to forge a new approach to resource mobilization and allocation that honors our commitments to the millions of people living with and at risk for HIV around the world. By embracing innovation, fostering new partnerships, and refusing to accept artificial tradeoffs, we can achieve the vision of ending AIDS as a public health threat.

This is a defining moment in the global fight against HIV. The international community must rise to the occasion, demonstrating the leadership and unity needed to ensure the success of HIV programs, despite the difficult circumstances we face. Now, more than ever, we must be bold, innovative, and united.

Conclusions

The current moment represents both an existential threat and an opportunity for the global HIV response. The gains of the past two decades – 25 million lives saved, 20 million of the 30 million people on treatment supported by PEPFAR, 5 million HIV-free births – stand at risk. Yet the crisis also compels us to reimagine and establish a more equitable, effective, and sustainable response.

The stakes of the current impasse are staggering. The February 1, 2025 limited waiver that restarted some essential HIV services during the foreign aid review period focused narrowly on antiretroviral therapy and prevention of mother-to-child transmission but excluded other key activities, including most HIV prevention programs [28]. ART does not distribute itself, and essential services cannot be executed with critical elements of these programs paused or terminated. The current pause in U.S. foreign aid funding has already resulted in clinic closures, staff layoffs, and service disruptions, causing patients to be lost to treatment. Treatment interruptions will lead to increases in drug resistance, AIDS-related deaths, and HIV acquisitions.

The fractured promise of the 2025 targets need not dictate our trajectory toward 2030 and beyond. With renewed commitment to the core values of diversity, equity, and inclusion; with evidence-based approaches to prevention and treatment; with unwavering solidarity with all affected communities; and with the moral clarity that has distinguished the HIV response at its best, we can still realize the vision of ending AIDS as a public health threat.

The path forward will not be easy, but the alternative – abandoning millions to preventable infection, illness, and death – is unacceptable. Now, more than ever, we must choose life.

Acknowledgements

Conflicts of interest

There are no conflicts of interest.