When the Levy breaks: Frailty and HIV at AIDS 2026

Ahead of AIDS 2026, AIDS activists confront frailty inflammation, metabolism and functional decline during the Trump era

By Roberto Antonacci, M.D., Alexandra Bridget Perkins M.D., Felipe Recalde, Frank Maresca, and David Miller

Antiretroviral therapy (ART) is transforming HIV from a fatal diagnosis into a chronic, manageable condition. Millions of people living with HIV/AIDS (PLWHA’s) are surviving into older age. By 2030, 65% of PLWHA will be 50 years or older. But this success comes with an urgent challenge- frailty.

As the global HIV community prepares to gather for AIDS 2026 this July, discussions about long-term survivorship are evolving beyond viral suppression alone. The April/May 2026 edition of POZ addressed the growing burden of frailty among older PLWHA, emphasizing that frailty is not a geriatric abstraction but a measurable driver of disability, healthcare costs, and declining quality of life.

Frailty is defined by diminished physiologic function, reduced resilience, exhaustion, loss of muscle mass, weight loss, and increased vulnerability. In HIV-positive populations, frailty often develops earlier and appears even in individuals whose viral loads are fully suppressed. This reality represents an important unanswered question in HIV medicine: how to prevent frailty in people with HIV/AIDS.

HIV frailty research is inseparable from international funding stability. Public health experts and global HIV advocates have criticized efforts to reduce U.S. contributions to international health programs, including the Global Fund for AIDS, TB and Malaria and foreign aid infrastructure, warning that instability in the Global South threatens continuity of HIV treatment in regions carrying disproportionate HIV burdens.

The Biology of Accelerated Aging:

For decades, HIV has been characterized by immune dysfunction and devastation.Today, the HIV treatment cascade is more complex. Despite antiretroviral therapy effectively suppressing viral replication, chronic immune activation and systemic inflammation persist. Research established that persistent inflammation results in accelerated aging.

The Women’s Interagency HIV Study and the HIV Veterans Aging Cohort Study Index show that frailty does not exist in isolation. It occurs with depression, multimorbidity, pain, cognitive vulnerability, and social instability. Research shows frailty among PLWHA being intertwined with malnutrition, cognitive impairment, polypharmacy, and geriatric syndromes that HIV clinics were not originally designed to detect.

PLWHA’s experience cardiovascular disease, osteoporosis, sarcopenia, cognitive decline, metabolic disorders, polypharmacy complications, and mobility impairment, leading to frailty years earlier than expected.

Several mechanisms are contributing to frailty including chronic immune activation despite viral suppression. persistent viral reservoirs in tissues, coexisting infections, metabolic dysfunction, excessive viscera fat accumulation and chronic inflammation. Social determinants of health, including isolation, poverty, stigma, food insecurity, and housing instability, also play a role. HIV frailty is not accelerated chronological aging: it’s biologically distinct, socially mediated, and often multidimensional.

From Survival to Function: HIV at AIDS 2026

HIV medicine has historically been focused on viral suppression, prevention of opportunistic infections, and immune recovery. Now, clinicians and activists are focusing on preserving function mobility, cognition, independence, metabolic health, and quality of life. Frailty is not a biological fate; It’s a warning sign.

Frailty research suggests that functional decline in HIV is dynamic rather than inevitable. Investigators with the NIH’s AIDS Clinical Trials Group (ACTG) reported that frailty fluctuates over time. Emerging studies such as Improving Physical Ability and Cellular Senescence Elimination in HIV (IPACE-HIV 2026), an ACTG phase 2 study, explored whether senolytic approaches improve frailty-related outcomes in PLWHA’s aged 50 and older.

“For decades we measured success in HIV almost exclusively through virologic suppression,” said Dr. Linda-Gail Bekker, former President of the International AIDS Society. “But viral suppression alone is no longer enough. The next generation of HIV care must address how people age, function, move, think, and live over time. Frailty is rapidly emerging as one of the defining challenges of long-term survivorship.”

Researchers are exploring senolytic therapies to interrupt inflammatory and degenerative pathways associated with HIV frailty. Recent studies identified senolytic therapies to eliminate senescent cells, which accumulate with chronic inflammation and contribute to organ dysfunction, immune dysregulation, frailty, and multimorbidity. PLWHA’s exhibits persistent immune activation and accelerated biological aging, increasing the burden of cellular senescence even in the setting of long-term viral suppression. Early studies of dasatinib and quercetin are examining whether senolytics improve physical function, inflammation, mitochondrial health, and markers of biological aging in PLWHA.

While the science is still early, the concept represents a transformative shift in HIV treatment: moving beyond viral control toward interventions targeting accelerated aging to preserve healthspan, mobility, cognition, and resilience.

Metformin, HIV, and the Search for Geroprotection

Metformin has become one of the most closely watched drugs in aging research because of its effects on metabolism, inflammation, insulin signaling, mitochondrial function, and cellular nutrient-sensing pathways. Studies have examined whether metformin can affect HIV reservoirs and systemic inflammation and influences monocyte epigenetic aging and immune pathways in virologically suppressed PLWHA, Metformin’s effects on immune activation and biological aging in PLWHA’s. Research has examined metformin’s effects on epigenetic age in people with well-controlled HIV, reflecting a broader effort to evaluate whether an inexpensive and familiar medication has geroprotective effects.

GLP-1 Drugs, HIV, Metabolism and Muscle

GLP-1 receptor agonists, including semaglutide, have opened another area of HIV aging research. These drugs are already transforming obesity, diabetes, cardiovascular risk, sleep apnea, and fatty liver disease care. For HIV patients, their relevance extends to lipohypertrophy, visceral adiposity, metabolic dysfunction-associated steatotic liver disease (MASLD), cardiovascular risk, chronic inflammation, oncogenicity, and frailty.

Recent analyses show that semaglutide improves metabolic parameters and reduces inflammatory markers in PLWHA. A randomized placebo-controlled trial reported reductions in markers of inflammation and immune activation, findings directly relevant to the biology of frailty.

Yet GLP-1 therapy also raises a frailty-specific caution. Weight loss can involve not only fat loss but also lean muscle loss. The ACTG reporting on SLIM LIVER noted that muscle volume decreased with weight loss. That nuance matters. For PLWHA demonstrating frailty, the goal must be metabolically healthy weight management that preserves strength, mobility, and function. GLP-1 drugs may become quintessential in HIV care, but in patients at risk for frailty nutrition, resistance exercise, functional monitoring, and careful attention to involuntary muscle loss has to be emphasized.

Cannabis and HIV Frailty

Cannabis is attracting attention from clinicians for treating frailty, after the recent federal rescheduling of medical cannabis by the Trump Administration. More than 60% of HIV patients reportedly use cannabis to address chronic pain, neuropathy, appetite loss, insomnia, anxiety, and nausea, which intersect with frailty and declining quality of life. Research has shown that cannabinoids influence inflammation, immune activation, and symptom burden.

Rescheduling has expanded research opportunities previously limited by regulatory barriers. But significant obstacles remain. Access to medical cannabis remains inconsistent nationwide, insurance coverage is generally nonexistent, and out-of-pocket costs are substantial for patients already burdened by chronic illness

The REPRIEVE trial...a phase 3 trial of 7,769 PLWHA’s receiving ART with low-to-moderate cardiovascular risk randomized participants to pitavastatin,showed that pitavastatin significantly reduced major cardiovascular events and modified inflammatory pathways preserving long-term function.

The implications extend beyond cardiology. PLWHA have elevated cardiovascular risk because immune hyperactivation, metabolic changes, and vascular injury are not captured by conventional models. REPRIEVE validated that HIV-associated chronic inflammation has clinical consequences.

Recent follow-up analyses continue to examine how pitavastatin’s benefits relate to lipid lowering and other pathways. A 2026 Lancet HIV analysis reported that REPRIEVE found a 36% reduction in adverse cardiovascular events with pitavastatin in HIV patients.

“The biology of chronic inflammation connects many conditions we are now seeing in aging people with HIV,” noted Dr. Steven Deeks of the University of California San Francisco. “Cardiovascular disease, frailty, sarcopenia, cognitive decline, and metabolic dysfunction are not isolated problems. They are interconnected manifestations of persistent immune dysregulation that we are only beginning to fully understand.”

Developing Early Clinical Recognition of Frailty

Frailty is still underrecognized and HIV guidelines continues to emphasize laboratory values- viral load, CD4 counts, and resistance profiles,markers that remain critically important, but fail to capture declining functional status. Routine frailty screening in HIV clinics remains inconsistent despite mounting evidence supporting its evaluation.

And these shifts will require significant funding. AIDS treatment activists are demanding biomarkers for HIV-associated frailty because the lack of uniform clinical endpoints is slowing progress across studies. AIDS 2026 is a platform to begin establishing consensus frameworks that guide international research.

At the same time, NIH funding cuts and political attacks on federally supported biomedical research threaten progress in HIV frailty research precisely when HIV frailty studies require expanded investment. Critics of the Trump administration’s public health agenda warn that cuts to HIV-related research infrastructure, prevention programs and grant funding are undermining long-term advances including frailty research among PLWHA’s.

Nutrition also remains a critically underappreciated component of HIV frailty management. Frailty is frequently accompanied by sarcopenia, unintentional weight loss, protein-calorie malnutrition, gastrointestinal disorders, and reduced oral intake, particularly among long-term survivors with multiple comorbidities. Enteral nutritional formulas have become increasingly important tools in HIV aging care to help preserve lean body mass and support physical resilience in patients at risk for functional decline.

But barriers remain significant. Reimbursement policies vary widely, and patients face substantial out-of-pocket costs for medically necessary nutritional support. As HIV populations age, frailty prevention strategies are beginning to include nutrition science alongside pharmacology, rehabilitation, and social support interventions.

Getting HIV frailty into Ryan White CARE Act during the Trump Administration

In the U.S. and Europe, more than half of PLWHA are now older than 50, a demographic shift reshaping the epidemic. Reviews of frailty in PLWHA’s emphasize that antiretroviral therapy has created a new clinical landscape in which geriatric syndromes must become part of routine HIV care.

Without proactive intervention, healthcare costs will continue to rise while disability rates increase and demands for long-term care expand. Existing health disparities worsen among key populations — Black and Latino communities, veterans, rural populations, women aging with HIV, and long-term survivors who have already endured decades of clinical and social adversity.

The Ryan White CARE Act (RWCA) and The End the Epidemic initiatives determine much of the U.S. response to HIV frailty. Designed during an era when HIV care centered primarily on survival, medication access, and treatment infrastructure, the RWCA now faces an aging HIV-positive population with increasingly complex medical, nutritional, functional, and psychosocial needs.

The future of HIV frailty research is increasingly vulnerable to political hostility toward federal biomedical research. The Trump administration repeatedly proposed cuts to NIH budgets, weakened public health infrastructure, and fostered a political climate that many researchers viewed as openly dismissive of scientific expertise. Those concerns have intensified with the growing influence of figures such as HHS Secretary Robert F. Kennedy Jr., whose long history of vaccine skepticism and promotion of medical misinformation has alarmed HIV researchers and infectious disease specialists. Activists warn that public health agencies are undermining decades of progress in HIV science precisely when frailty research requires sustained long-term investment.

Researchers are also worried that the leadership associated with NIH Director Jay Bhattacharya, whose emphasis on reducing what he describes as institutional orthodoxy within public health agencies has generated anxiety among HIV advocates about the future stability of federally funded prevention, frailty and disparities research. Scientists working in HIV and gerontology fear that ideological battles over public health priorities is inhibiting critical work on frailty biomarkers, inflammation, and interventions targeting long-term survivorship. The era of mass demonstrations by ACT UP in Bethesda at the sprawling campus of the NIH and the FDA in Rockville, demanding critical research and accelerating drug development are long gone…this fight is destined for the auditoriums in Rio this July.

These changes are unfolding amid renewed uncertainty surrounding federal HIV policy. During the Trump administration, efforts to weaken the Affordable Care Act, reduce Medicaid spending, and shrink federal health programs policies HIV advocates consider

threats to the healthcare safety net supporting PLWHA’s, arguing that the administration treats public health funding as politically expendable despite the disproportionate impact such cuts have on HIV patients, vulnerable populations and rural communities.

The policies of Robert Kennedy at DHHS further intensified fears among HIV organizations that evidence-based public health policy have become subordinated to ideological agendas and distrust of scientific institutions. For PLWHA’s already facing housing insecurity, nutritional instability, and complex chronic illness, instability in federal HIV policy carries potentially devastating consequences

Long-term survivors are now confronting sarcopenia, cognitive decline, mobility impairment, polypharmacy, social isolation, food insecurity, and housing instability simultaneously. Ryan White programs have excelled at coordinating HIV treatment access and supportive services, but frailty requires expanded integration of geriatric medicine, rehabilitation services, nutritional support, mental health care, transportation assistance, homecare, and multidisciplinary functional assessments.

HIV frailty is a healthcare infrastructure issue, demanding public health reimbursement policy and influencing the quality of life of aging PLWHA. RWCA transformed HIV in the U.S. from a fatal disease into a manageable chronic condition over four decades. Addressing HIV frailty i ensures long-term survivors are able to age with dignity, mobility, support, and functional independence. Without prioritization, frailty research remains fragmented across geriatrics, oncology, infectious disease, endocrinology, cardiology, rehabilitation medicine, and behavioral health.

HIV Frailty: A New Priority for Ending the Epidemic:

Managing HIV frailty effectively requires interdisciplinary collaboration among infectious disease specialists, geriatricians, physical therapists, nutritionists, neurologists, mental health professionals, rehabilitation experts, pharmacists, and social workers. HIV care systems proved extraordinarily effective at responding to opportunistic infections and viral management.

The research on metformin, GLP-1 receptor agonists, pitavastatin, senolytics, inflammation, epigenetic aging, and HIV reservoirs demonstrates that frailty may be approached from multiple angles. Interventions targeting metabolism, inflammation, cardiovascular risk, cellular aging, and muscle preservation are emerging.

The increasingly nationalist and anti-institutional approach to global public health under Trump-aligned leadership — amplified by Kennedy’s skepticism toward international health initiatives and Bhattacharya’s critiques of federal scientific institutions — is weakening international HIV collaboration at the very moment HIV frailty complications are becoming a universal concern while HIV researchers argue that frailty research requires greater international coordination, not political retrenchment or reduced investment in global public health systems.

HIV Frailty at AIDS 2026

“We are entering an era where preserving healthspan may become just as important as extending lifespan,” said Jules Levin, founder of the National AIDS Treatment Advocacy Project. “The HIV community must aggressively pursue research into frailty, nutrition, muscle preservation, cognition, inflammation, and aging biology. Otherwise we risk creating a generation of long-term survivors who are living longer but struggling with preventable disability and loss of independence.”

HIV-related frailty is not inevitable. It is measurable, modifiable, and increasingly treatable. At AIDS 2026 activists and clinicians hope the next era of HIV medicine will not be defined solely by suppressing the virus but toward the active development of multicenter studies, prevention frameworks, therapeutic trials, functional outcome measures, and implementation strategies to facilitate

Frailty is becoming the most neglected story at AIDS 2026, at the very moment when this evolution converges around a unified goal: extending both lifespan and healthspan for PLWHA’s. AIDS 2026 is an opportunity — and arguably an obligation — to help lead that transformation and elevate HIV frailty research from an emerging subspecialty concern to a central pillar of HIV agendas

About the Authors

Roberto Antonacci, M.D. is a Board Certified Radiation Oncologist, a member of the International AIDS Society and VOCAL-NY, an HIV advocate, and a recognized public health leader whose work has focused on advancing care models, social justice prevention strategies, and long-term survivorship for PLWHA. Dr. Antonacci is the Co-Chair of the New York Medical Cannabis Industry Association (MCIA) and a member of VOCAL NY, The NY Public Health Association and the International AIDS Society.

Alexandra B. Perkins, M.D. is a physician with dual Board Certification in Diagnostic Radiology and Integrative Medicine. She is an experienced clinical leader in women’s health, population based screening, and development and implementation of integrative therapeutic protocols to address chronic complex disease.

Felipe Recalde is a global health advocate whose work centers on health equity, international healthcare policy, patient engagement, and expanding access to evidence-based healthcare. His writing and advocacy focus on strengthening healthcare systems and advancing equitable health outcomes worldwide.

Frank Maresca is a board member of Health People, a leading AIDS Service Organization in the Bronx, NY and a longtime AIDS advocate, focused on the economic dynamics of contemporary health disparities.

David Miller is an AIDS treatment activist and journalist focused on HIV aging, coinfections, emerging therapies, and policy issues affecting PLWH. He is the former Co-Chair of the Cornell AIDS Clinical Trials Group Community Advisory Board and has served as the Co-Chair of the New York City HIV Planning Council Community Advocacy Group. David has served on the Board of the AIDS Institute and the Bronx HIV CARE Network. A veteran of ACT UP New York, his work emphasizes the intersection of science, access to care, and quality of life for PLWH.He is a member of the International AIDS Society, the American Public Health Association, The International Association of providers in AIDS Care, The National Minority AIDS Coalition, The HIV Medicine Association, the American College of Epidemiology,