In roughly nine days I’ll be standing in the Poster Hall at AIDS 2026. It’s a fluorescent-lit purgatory of white foam boards and academic jargon, the exact spot where high-stakes science goes to die in public. The air is going to taste like lukewarm coffee and industrial-grade desperation. You’ve got Ph.D.s in polyester suits guarding their data like religious relics, waiting for a nod from the gods that never comes. Right now the federal government is incinerating millions of dollars to work out whether cannabis is the savior or the executioner of the HIV-ravaged brain, and you’d never know it from the coverage. The findings are heavy. The stakes are visceral. And the HIV media is face-down in a gutter, asleep at the wheel. Nobody’s writing it down, and that’s the goddamn scandal.

Scientific priorities don’t talk. They bleed cash. Enter SCORCH, the Single-Cell Opioid Responses in the Context of HIV. It sounds like a black-ops weapons program. It’s actually a bureaucratic leviathan built to map the brain one twitching cell at a time. The thing is steered out of NIDA’s Division of Neuroscience in Rockville by the high priests of the federal checkbook, Susan Wright and John Satterlee. Back in 2023 they cut an $11.6 million check to Shomi Ndhlovu’s crew at Weill Cornell to see how cannabis warps or welds infected tissue. Tens of millions poured into the void, and the output is a run of posters pinned to the back wall of a convention center. Twenty-three thousand people will swarm IAS/AIDS 2026 and not one of

On paper, NIDA and NIAID are shaking hands. In the trenches, the SCORCH findings are hitting a brick wall. They aren’t translating to the AIDS Clinical Trials Group, the ACTG, the heavy hitters who actually run the trials that decide whether you live or rot. The ACTG’s Neurology Collaborative Science Group, chaired by Felicia Chow of UCSF, sits on the far side of a bridge nobody has built yet. No one on the executive committee is forcing the connection. So we watch tens of millions of people march toward cognitive decline while the researchers refuse to read off the same map. It’s a clinical failure dressed up in the robes of “process.”

And don’t let anyone tell you the data isn’t there. It’s piled to the ceiling. It just never leaves the building. Out at UC San Diego, Ronald Ellis and his colleagues pulled spinal fluid from 263 people and found that the daily cannabis users living with HIV had the calmest brains on paper. Their inflammatory chemokines, MCP-1 and IP-10, dialed down toward the levels of people who never carried the virus at all, and the calmer the fluid, the better they learned. It’s a cohort study, not a randomized trial, so association is the asterisk the scientists will always wave at you. But the signal is loud, and Ellis’s own review lays out the mechanism: cannabinoids tamping down the smoldering, body-wide inflammation that drives heart attacks, dementia, and death in people aging with the virus.

Then there’s the pill problem. Amy Justice at Yale has spent a career quantifying what it costs to grow old with HIV, and her polypharmacy data is a quiet horror show. Stack six drugs in an aging HIV patient’s medicine cabinet and you get roughly seven documented interaction pairs, against about one you’d expect by chance. This is the population SCORCH is supposed to protect. People already drowning in prescriptions, already aging a decade ahead of schedule. And the one intervention half of them are already self-administering, cannabis, is the one nobody in the clinical networks will study with any urgency.

Here’s the true absurdity. The system treats “cannabis” like a single grey blob. Most studies, including the elegant UC San Diego work on CBD and the brain’s TREM2 repair signal, use sterile CBD isolate. It’s safe, it’s boring, and it’s nothing like what humans actually put in their bodies: CBN, CBG, THC, and terpene profiles that would make a chemist weep. Ndhlovu’s Cornell trial is our best shot at a real answer, but here’s the catch. Nobody knows which cultivar they’re actually using. Not the dispensaries, not the regulators, not the industry.

And that’s the part that should make you throw your coffee. The tools to answer “which cannabis” already exist. Germplasm banks and DNA-marker fingerprinting can pin a plant to its genetic identity and its chemical profile. We know in black and white that the folk names are a lie. What sells as “Blue Dream” at the dispensary counter is, genetically, a coin toss. “Which cultivar?” isn’t an unanswerable question. It’s an unasked one. Answering it is exactly the applied science that outfits like Buffalo’s Dent Neurologic Institute, and our own affiliated ventures at GEM and Compound Genetics, exist to force onto the record.

Dent is worth pausing on, because it’s proof the clinical signal survives contact with real patients. In a chart review of 204 of their neurology patients, average age 81, roughly seven in ten reported that medical cannabis helped, and a third of them cut their opioid dose. It’s a retrospective review, not a gold-standard trial, but it’s exactly the kind of grounded, human evidence that the SCORCH machine, for all its millions, still refuses to connect to the people who need it.

Understand the scale of what’s being ignored. HIV-associated neurocognitive disorder isn’t some rare complication. The largest meta-analysis on record puts it at 42.6% of people with HIV, some 16 million human beings. And the population is graying fast. By 2021 more than half of Americans living with diagnosed HIV had already crossed 50, and the CDC now projects the ranks of the 75-and-older could swell as much as sixfold by 2040. Every one of those people runs roughly $420,000 in lifetime care, a bill that climbs, not falls, the longer they live. A brain you can’t keep is a patient who can’t adhere, can’t work, can’t live alone. This isn’t a footnote to the epidemic. It’s the next front of it, the same convergence of frailty, inflammation, and neglect this publication mapped in When the Levy Breaks.

The shift of medical marijuana toward Schedule III has kicked the doors open, but that window won’t stay propped forever. Federal funding is a political knife fight, and anything touching drug use and HIV is always first onto the chopping block. In the spring of 2025 the administration terminated $1.8 billion in NIH grants in a single month, and more than 200 HIV-related grants were killed outright. Congress preserved the topline NIH budget for 2026, but hundreds of terminated grants were never restored. If this science doesn’t mature into real therapies, FDA-approved drugs that reach a human hand, it’ll get swept away in the next budget brawl. We have to drag these findings out of the poster hall and onto the podium before the machine pulls the plug. In nine days I'll be at the microphone in Rio asking why. Somebody has to.

Getting myself to Rome and reporting on the conference was as much of a challenge as devouring the enormous amount of research shown. We could spend months reporting on all the innovative advances presented at IAS 2011 and, in a number of venues, much of this vital knowledge has and will be appearing in the HIV media, both on the Web and in print, for months to come.

The sifting out of hundreds of presentations to identify the most compelling issues that, as a community, we need to pay attention to, requires some insight into how advances in research will translate to changes in treatment. In four days, conference attendees were drowned by fifty sessions, nine plenaries, 3,552 abstracts, and thirty-one satellite meetings.

The 6th IAS Pathogenesis Conference was important enough that Rep. Alcee Hastings (D.-FL) issued House Resolution 360 on the conference, which noted the dangers we’re facing from emerging drug resistance, including the spread of XDR TB (extensively drug resistant tuberculosis). This resolution is a clear sign that some of our more intelligent, responsible legislators are paying closer attention to the translation of the science that can help end this plague.

One shuddering event, just days before the conference, was the announcement that the Italian government has no plans to continue the National AIDS Research Program at the Istituto Superiore di Sanità (ISS), the equivalent of the U.S. National Institutes of Health that, at its peak in the 1990s, received €25 million a year. Italy is the only G8 country that has not recently contributed to the Global Fund to Fight AIDS, Tuberculosis and Malaria. A lot of very important research is going to be lost, research we all need now.

How fast can you run?
On Saturday, July 16, a session called “The New Concepts in HIV Immunopathogenesis, Treatment and Vaccines” drew key international opinion leaders who presented their innovative views and stimulated debate to help advance four critical areas of research in HIV infection: immunopathogenesis, new concepts in vaccine strategies, eradication of virus reservoirs, and molecular mechanisms of viral control. The meeting prompted serious discussion between prominent vaccine and treatment specialists and basic scientists, providing a unique opportunity to cross-fertilize these different fields.

The SHE (Strong, HIV positive, Empowered Women) Programme European Launch spoke to how much patient advocates, despite our reduced numbers, are still very influential in driving the clinical agendas in our interests.

Another important event at IAS Pathogenesis was the launch of a community based study of women living with HIV/AIDS in Europe. The SHE (Strong, HIV positive, Empowered Women) program is developed and steered by an independent advisory board, comprising advocates, women living with HIV, and other HIV healthcare experts composed of forty women representing close to forty advocacy groups from across eight European countries including Belgium, France, Germany, Italy, Poland, Portugal, Spain, and the United Kingdom. The program provides support to women living with HIV, aiding them to empower themselves to improve the quality of their lives, including getting the most out of their healthcare services and to create an effective dialogue with healthcare professionals. This will be a groundbreaking study of the challenges that HIV-positive women in Europe are facing; it addresses the clinical disparities between clinical outcomes we see between men and women and aims to engage policymakers to consider the special issues confronting women living with HIV, thereby increasing awareness and understanding throughout Europe. The SHE programme is developed at the discretion of the faculty and is funded by Bristol-Myers Squibb.

Another incredibly important meeting, “Towards an HIV Cure” Global Scientific Strategy–International Working Group & Stakeholders’ Advisory Board meeting, was

held on Thursday, July 21. Following the success of the workshop “Towards a Cure: HIV Reservoirs and Strategies to Control Them,” held in conjunction with the XVIII International AIDS Conference (AIDS 2010) in Vienna in July 2010, IAS decided to continue to mobilize the scientific community and guide the development of a Global Scientific Strategy Towards an HIV Cure. An international scientific working group is developing a draft global scientific strategy in cooperation with a stakeholders’ advisory board. Those two groups will meet after IAS 2011 to define research priorities in the field of HIV cure research. You can find a full list of the stakeholders membership on-line at: www.iasociety.org.

The Fourth International Meeting on HIV Infection and the Central Nervous System–Treating the Brain in the HAART Era took the opportunity of so many HIV clinicians and scientists gathered together in Rome to bring the issues of neurological manifestations, including HIV-dementia to the forefront of the discussions. Among the most threatening complications of HIV infection, although the incidence of neurocognitive impairment associated with HIV brain infection and progressive multifocal leukoencephalopathy has dramatically decreased among people receiving combination antiretroviral treatments, these complications are among the most frequent and devastating complications of HIV currently observed.

Despite significant progress in understanding the pathogenesis of these complications and efforts to translate this knowledge into clinical practice, it was made clear at the meeting that optimal management tools in HIV neurology are still lacking. At this meeting, attendees began to address unsolved issues, discuss clinical strategies and the need to begin to examine studies and interventions PLWHA’s currently have available.

Part of my work at the conference was helping to put on the NAPWA Treatment Horizons: Pathways Towards a Functional Cure satellite symposium, which was produced in conjunction with staff from Health People, an AIDS service organization located in the South Bronx, the epicenter of the epidemic in North America and one of the poorest communities in the U.S. The satellite symposium showed data on therapeutic vaccines, gene therapy, new antiretrovirals in development, and advances in treatment that are backed by good clinical rationale and experience. Close to a dozen new developments in clinical research to change the course of the epidemic included:

• Sandy Pijaia, MD, presenting on TBR652, a Phase II chemokine antagonist and Julian Chick’s presentation on Avexa’s long-awaited third-generation nuke, ATC.
• Another very promising antiviral maturing in development, ATC, a Phase III NRTI, was presented by Susan Cox, PhD, at Avexa.
• Virxsys presented on VRX 496, a gene therapy in Phase II clinical development, Vacc4x, a therapeutic vaccine in Phase II being developed by Bionor Pharma along with FIT-06 (FIT Biotech), which is also in Phase II development.
• Aphios presented data on APH-0812, a therapy for treating HIV latency, a new approach involving histone deacetylases (HDACs) inhibitors and non-tumor promoter Protein Kinase C (PKC) agonists.

Gary Blick, MD, who heads World Health Clinicians, a nonprofit, presented on MuscleGel, a new whey protein supplement that is getting support for Medicaid approval from a number of advocacy groups because of its ease of use. BioK+, the makers of CL1285, a probiotic, joined in on a presentation on therapeutic nutritional supplements that are so often overlooked. Both protein supplementation and probiotics are very helpful in managing side effects of ARVs and can help with HIV-infection-related weight loss, which is supported by a lot of data.

Disappointing was the lack of new data on the viral decay accelerator from Koronus or Adaptimmune, Argos Therapeutics’ autologous cell therapy and the research from Mike McGrath, MD, at Pathologica. Again, we can presume the financial climate is having an impact on very promising research that can save our lives.

The trends in HIV research in this stunningly unstable economy are greatly affecting the continued future of important research that is critical for the future of further advances to end the AIDS pandemic. We’ve all seen how therapeutic success has driven research of a cure closer to reality but more basic understanding of how to control HIV has to become better focused and translate into studies. HIV vaccines continue to remain out of reach, but it’s clear that groundbreaking ideas are coming forward into further investigation that could also contribute to curing HIV.

So what do we do now?
• Join International Treatment Preparedness Coalition (ITPC), ATAC and other organizations, both global and local, to get ready for the 2012 Conference on Retroviruses and Opportunistic Infections (CROI 2012) and the upcoming HIV Persistence Workshop in St. Maarten, West Indies, from December 6–9, 2011.
• Join other AIDS treatment activists and continue to learn more and report on scientific and clinical advances presented on the IAS Pathogenesis Conference Web site. There’s so much more research that demands more of our attention.
• Tell our legislators to find support for new strategies that may lead to advancing our understanding of how HIV works.
• Have a great idea? Know a clinician who does? Check out the new program at the NIH at: www.cnihr.org, which sponsored an instructive meeting on grant application programs focused on HIV eradication.

As we watch the horn of Africa experience a very unnoticed apocalypse, while our national economy has begun to resemble the convolutions affecting much of Europe, it is important for people with HIV/AIDS to defend our hard-won gains, to increase our knowledge about what’s in the pipeline, and to advance the research that may save our own lives, as we see from the first actual cure that HIV can be wholly defeated. A cure seems just within reach. The question now is how far we can all extend ourselves.

David Miller is a member and former co-chair of Cornell ACTG Community Advisory Board, as well as a member of the Campaign to End AIDS, The AIDS Treatment Activist Coalition and GNP+, the Bronx HIV/AIDS Advocacy Network and a board member of The AIDS Institute. David works with NAPWA and the Health People HIV/AIDS Treatment/Policy Education Advocacy Demonstration Project in the Bronx. David was a member of ACT UP NY.

This article originally appeared in aumag.org

“Let’s be honest,” I said early this morning on my first call to one of my collaborators. “There’s not a solitary person heading to Montreal this July who’s not absolutely convinced all hell is coming at us at AIDS 2022.” We’re dealing with the most significant European HIV diaspora in the history of the epidemic, compounded by the intersections of COVID-19, the war that’s consuming the European illusion of stability, and the subsequent famines, all conspiring to undermine the hard-won gains that antiretroviral therapy and the evolution of programs taking precision aim at key populations affected, infected and disproportionately representative of the disparities driving new infections.

COVID-19 and the war in Europe will be at the forefront of AIDS 2022. I’d been at far too many conferences over the past three decades to take anything for granted. However, the fact that thousands of people from around the world are still coming to Montreal to present and discuss advances in AIDS research and treatment leaves me awestruck — even while the dimensions of my carry on defy my best efforts to not be left facing the inevitable horror that international travel has become.

Before the war, Ukraine was the epicenter of HIV in Europe. Today, Ukraine still has one of the highest rates of HIV in the world. With the war continuing and millions of refugees fleeing Ukraine to be housed in refugee camps where disease is spreading, the co-intersections of COVID-19 and AIDS as a result of this war mean severe increases in HIV in Eastern Europe. Add food insecurity to that horror — meaning refugees are not getting proper nutrition — and we have a devastating scenario at hand.

In sub-Saharan Africa, where the burden of HIV disease is also greatest, a consistent rise in food insecurity has left an estimated 258 million people facing famine, with an additional 605 million moderately or severely food insecure. The Intergovernmental Panel on Climate Change recently issued a report highlighting how climate change is already adversely affecting food security regarding food availability, access, and nutrition.

Every program that has served as a cornerstone of the global response to the AIDS crisis is being challenged. PEPFAR, The Global Fund for AIDS, Tuberculosis, and Malaria, and even the Ryan White CARE Act all face unprecedented pressure to maintain programs, innovate, and increase their reach while competing for resources against an unprecedented number of spending initiatives. Meanwhile, the integration of food security interventions into HIV treatment programs is essential to curtail the HIV epidemic and improve the health and quality of life of those infected.

It’s in the interest of people with AIDS and in the interest of the greater good to shift some of our attention to the global famine at AIDS 2022, preserving the UN Sustainable Development Goals (SDGs) of ending hunger by addressing the data demonstrating that antiretroviral therapy is being undermined by the malnutrition that’s at the forefront in the Sahel region — as well as the South Bronx.

Food security is now at the forefront of the lives of people with HIV as food prices have risen 12.6%, exacerbating global hunger. In contrast, Russia has weaponized global food supply chains. Conflict always goes hand in hand with food insecurity. Still, the supply, and frankly the contemporary composition of Humanitarian Daily Rations, currently deployed by the Defense Logistics Agency and the NATO Support and Procurement Agency (NSPA), have limited utility in the war in Ukraine. They are predictably inadequate to address the explosive patient populations now becoming refugees because of Russian shellfire, regional conflicts, climate change, and global inflation.

Next-generation enteral formulas and Ready to Use Therapeutic Foods to treat Serious Acute Malnutrition (SAM) are somehow making their way to market, despite the supply chain crisis. New enteral formulas like ACERT, ENU, and Peptide 1.5 are demonstrating superior clinical efficacy to past interventions to guard against involuntary weight loss by delivering nutrition that encourages immune reconstitution, sparing patients’ further exacerbation of cardiovascular disease and insulin intolerance-non-communicable diseases that HIV key populations are already at high risk for. As food prices continue to rise, previous studies on managing HIV nutrition enteral formulas will be critical. Studies have shown that food insecurity — a significant barrier to ART adherence and retention associated with adverse clinical outcomes, including incomplete HIV RNA suppression, CD4 declines — increased opportunistic infections, hospitalizations, and mortality.

Innovations
As stated in a 2014 paper written by the Food and Nutrition Technical Assistance III Project (with support from the Office of Health, Infectious Diseases and Nutrition, Bureau for Global Health, and USAID), “weight loss and malnutrition are associated with HIV, and low body mass index at diagnosis of HIV infection significantly increases the risk of mortality. Chronic weight loss occurs in around 20 percent of patients with HIV, and severe weight loss is one of the strongest indicators associated with morbidity and reduced survival, even with antiretroviral therapy. Evidence has shown that macronutrient supplementation positively affects weight gain and adherence to medication in people living with HIV.” Eight years later, this remains a life-threatening issue globally.

Further evidence that proper base nutrition supplementation given to patient populations can reduce or eliminate malnutrition — and result in healthy weight gain — is provided by a clinical study conducted by the Plant-Based Enteral Formula (PBEF) pioneering company, Kate Farms.

The study, Weight Gain in Oncology Patients using a Plant-Based Oral Nutrition Supplement, included thirteen cancer patients. Of the thirteen patients, nine had at least one follow-up assessment from a dietitian after adding PBEF to their nutrition regimen. Of the nine, all either gained or maintained weight. Six gained, and four showed an increase in BMI. Of those with documented weight gain, the average was 3.5 kilograms. Of those with a documented increase in BMI, the average was 1.53 points over an average of 3.5 months. The nine patients received an average of 44.6% of their daily calories from PBEF. One of the nine was on PBEF for a 12-month period and experienced a 9.09-kilogram weight gain and a 2.8-point increase in BMI during this time. Significantly, nutritional status changed from “severely malnourished” to “no clinical signs of malnutrition.”

Conclusion: Weight maintenance, weight gain, and tolerance using a plant-based enteral formula were demonstrated in this small cohort of adult oncology patients.

Since medical treatment can be interrupted when patients experience significant weight loss, dehydration, or clinical malnourishment, the results of this study have important ramifications. Without proper supplementation, these patients would have continued to decline nutritionally. [The small sample size is a limitation to this study and supports the need for a larger trial.]

One immediate reform activists are hoping for is greater recognition and support of HIV nutrition among the American Society for Nutrition & ASPEN with the HIV Medical Association, IAPAC, The American Academy of HIV Medicine, and the IAS.

AIDS 2022 is going to be pulled in a dozen directions, between monkeypox, COVID-19, the advance of long-acting antiretrovirals, the Ukraine HIV+ refugee diaspora, the continued pursuit of a cure in the HIV Research Collaboratories, the AIDS Clinical Trials Groups, the Military HIV Research Program (MHRP), and other publicly sponsored research programs. We’re going to be awash in new data. The 24^th International AIDS Conference in Montreal this July is going to be the location where we affirm the resilience of the science and advocacy that’s characterized the AIDS crisis by demanding more advances, more improvements to HAART, more access to treatment… and for millions of people with HIV and their families, demands for more calories and more micronutrients as T-cell counts are going to be proportionate to access to clinical nutrition. Global food security becomes a dominant predictor of our continued collective community’s survival.

This article originally appeared in healthhiv.org

By David Miller and Noreen Griffin.

At IAS 2017 in Paris last July, delivering treatment, medicines, and other HIV-related services to the most vulnerable patient populations in resource-poor, distressed, and unstable nations should have been a matter of urgency. But there were no declarations, no condemnations, and no calls for immediate action.

More than a decade ago, Venezuela was lauded for its treatment program. Now, more than a decade into its political and economic crisis, Venezuela’s oil revenues account for 95% of the country’s export earnings and the precipitous decline in oil prices has helped plunge Venezuela ever deeper into crisis. The corrupt and increasingly dictatorial regime of President Nicolás Maduro Moros, has only accelerated the country’s decline.

Venezuela’s economic crisis is a tragic example of impact of domestic instability on the testing, treatment, and care of people living with HIV and on the worsening global HIV pandemic. Venezuela’s entire healthcare system is critically short of medication, including life-saving anti-HIV drugs. Despite pleas for immediate assistance from the Global Fund to Fight AIDS, Tuberculosis and Malaria, no measurable degree of help has arrived. The World Bank continues to classify Venezuela as a high-income nation and the Global Fund “is not in a position to grant any exceptions from its rules,” according to its Executive Director Mark Dybul and Norbert Hauser.

An estimated 110,000 people in 2015 were living with HIV in Venezuela, and at least 63,000 of them had started antiretroviral (ARV) treatment, says Feliciano Reyna Ganteaume, whose Caracas-based nonprofit Acción Solidaria supplies HIV-infected people with ARVs. “[The situation] is much worse than one can describe,” he says. “When the government does take action, drug orders are placed late and not paid for on time, causing interruptions that have lasted more than months… There is not even 1 month without our receiving complaints of lack of one or more ARVs from one or more Venezuelan states,” he says. In addition, reagents for the tests needed to monitor people on treatment are in short supply.

Economic instability has greatly affected basic HIV treatment and care for people living with HIV in Venezuela. Diagnostics such as CD4 and drug resistance testing have become all but non-existent and stocks experience a lack of resupply, lasting a month or two, approximately every two to three months. Basic laboratory services and drugs such as antibiotics have become unavailable. HIV testing for mothers and ARVs to prevent mother to child transmission are in inadequate supply, resulting in late-stage diagnosis and contributing to an increased rate of mother to child transmission. Maria Eugenia Landaeta, the chief of infectious disease at the teaching hospital who oversees the HIV program for 5,600 patients, reports that a small group of AIDS physicians has been scrambling to hold it together for years. “The HIV and TB programs were the last to deteriorate,” she said. “We have tried to defend the program in all possible ways.” (https://www.theglobeandmail.com/news/world/in-venezuela-a-once-leading-aids-program-lies-inruins/article35417359/)

At IAS 2017, while the refugee crisis in Europe was a key issue of reference, with numerous posters and presentations featuring the challenges of internally displaced persons, the Venezuelan crisis went virtually unmentioned, despite the knowledge that tens of thousands were going without life-saving medications. The Venezuelan Society of Infectious Diseases (SIV) issued a statement back in November of 2016 announcing that supplies of key drugs used for the treatment of HIV were dangerously low and in danger of stock-out. These drug shortages mean that there are currently no treatment options considered first-rate under international guidelines. “The shortage of antiretroviral drugs and reagents makes it impossible to control the HIV/AIDS epidemic in the country, making it difficult to control the transmission of the virus from the mother to her children and in the general population,” Maritza Landaeta, a senior member of SIV, said. “We are seeing a collapse in the public health system. Venezuela is witnessing a miracle, a miracle of destruction.”

Vulnerabilities continue to mount for displaced persons, who are increasingly exposed to the social drivers of HIV, Hep C, and co-infections. In addition, instability in countries throughout Africa and South America also contributes to an unsteady state of universal access to HIV testing and treatment which drive the continued spread of HIV.

We have learned the hard way the consequences of complacency in the response to global pandemics. The epidemiological dimensions of Venezuela’s current descent into chaos should concern all researchers, activists, and policy makers in the Americas. HIV and its co-morbidities thrive on poverty, instability, and displacement. Several presentations at IAS 2017 focused on the impact of specific instabilities and policies on the treatment and care of its citizens, in particular, at-risk populations such as refugees, migrants and asylum seekers.

One study found a wide range of disparities negatively affecting access to testing and treatment of key at risk and populations. The disparities centered mainly on migrants, asylum seekers, and refugees. The study resulted in a website called “Barring the Way To Health” (https://www.gnpplus.net/our-solutions/barring-the-way-to-health/)

Another study at IAS 2017 analyzed a pilot program initiated by Medecins Sans Frontiere in rural areas of Yambio South, Sudan, to test the feasibility of providing HIV testing and counselling and ARV initiation in regions of chronic conflict. Five mobile teams offered testing and counselling and same day ART initiation to those who tested positive and data over a 17- month period was analyzed. Counseling sessions were provided which included instructions on what to do during times of active conflict including a constituency plan that provided access to ‘go bags’ containing a three-month supply of ARVs. During the study, there were several episodes of instability where the contingency plan was activated.

Results of this study found that levels of ARV retention (86% at 6 months and 81% at 12 months) and viral load suppression (85% below 1000 copies) were comparable to clinic settings. Throughout the study, 13,872 people were tested for HIV, of which 442 (3.2%) tested positive. Of the 442 positive individuals, 344 (77.8%) were started on ART.

A third study assessed the feasibility of providing home-based HIV testing in sub- Saharan refugee camps. Visits were made to 319 homes that reported a total of 566 individuals living in the homes, during a one- month period of time in the Nakivale Refugee Settlement. During a total of three visits per home, researchers were able to reach 507 individuals in 292 homes. Of these, 378 (75%) agreed to be home-tested and received their results. There were 7 (1.9%) individuals who tested positive for HIV. Researchers found that people were more likely to agree to be tested if there were others present. The authors concluded that home-based HIV testing is feasible in refugee camp settings.

There is robust data demonstrating that effective service delivery can be conducted for large HIV patient populations struggling in distressed economic and political circumstances. Global Fund’s ban on HIV-related assistance to ostensibly high-income countries is contributing to several regions of risk. The policy has previously led to cuts in HIV/AIDS funding to several Eastern European countries, a move heavily criticized by advocates in those countries. As international assistance for HIV/AIDS has steadily dropped over the past few years, the Global Fund has pushed harder on governments to foot their own bills. The unfolding crisis in Venezuela, and its dire implications for the diagnosis, treatment, and prevention of HIV, should shake the complacency of the Global Fund and other international aid organizations. In an ever more global community, Venezuela’s humanitarian crisis will not long stay Venezuela’s alone. We will help ease Venezuela’s pain, or we will eventually feel it ourselves.

This article originally appeared in Panaware panaware.wordpress.com/

By David Miller and Chad S. Johnson Esq

Many AIDS 2017 attendees in Paris were disappointed by the neglect of a timely, critical focus on the HIV challenges in Venezuela caused by the abject failure of governance, human rights, and the rule of law in Caracas. With the country falling apart and people unable to obtain essential HIV medications and basic medical supplies, the lack of a concerted effort to address this urgent human tragedy at AIDS 2017 seemed like an astounding failure by the most powerful stakeholders in the epidemic. However, an equally pressing dynamic has existed for years without mainstream media coverage in many countries in Eastern Europe and Central Asia (EECA). While not making the daily headlines, the EECA region has the highest new HIV infection rate in the world at 57% between 2010 and 2015 according to AVERT, a statistic highlighted at the AIDS 2017 teaser session on the upcoming 22^nd International AIDS Conference in Amsterdam, Netherlands underway during the next days in July 2018 (AIDS 2018).

The AIDS 2017 session emphasized that one of Amsterdam’s top five objectives is to change the dynamic in the EECA where governments, institutions, orthodox religions, society, law enforcement and criminality, and international organizations fail vulnerable populations. Session participants noted that this EECA problem was on the agenda during the 19^th IAC in Vienna in 2010, a conference now deemed a failure in this regard. Leading up to AIDS 2010, the WHO reported that the epidemic in Eastern Europe “… can be ascribed to government intransigence, public ignorance and the criminalization of risky behaviors, compounded by poverty, social exclusion and political and economic turmoil.” These conditions have not significantly changed in Eastern Europe and continued to be mirrored in Central Asia.

Consequently, AIDS 2018 Local Co-Chair Dr. Peter Reiss of Amsterdam and International Co-Chair Dr. Linda Gail-Bekker of Cape Town, South Africa, committed to shine a spotlight on people left behind in the international response to the AIDS epidemic and to prompt a vigorous discussion about the reasons that the EECA region is an outlier in the progress seen around the world. The theme of AIDS 2018, “Breaking Barriers, Building Bridges,” speaks to some of the unique contributing factors beyond unsafe sexual practices, including language, culture, lack of human rights and freedom of information, and “relative” prosperity (and with it, non-qualification for various international assistance programs for middle-income nations). Additional factors on the rise in the EECA region include IV drug use in countries disapproving of needle-exchange programs, migration of female sex workers who are shamed into the shadows by conservative societies, and the refugee crisis and its health consequence.

The organizer of the session, the Dutch Ministry of Foreign Affairs, represented by Mr. Lambert Grijus, the Dutch Ambassador for Sexual and Reproductive Health & Rights and HIV/AIDS, articulated rights- and community-based approaches to more effectively reach key populations in the EECA region, along with putting mechanisms in place to hold politicians accountable in regional and international diplomatic settings for shortcomings in HIV-related awareness, funding and policy. Dr. Michel Kazatchkine, former Director of the Global Fund and currently the UN Secretary-General Special Envoy on HIV/AIDS in Eastern Europe and Central Asia, also underscored the importance of aggressive work with top-level politicians as key to breaking the log jam in the region. Unless governments acknowledge and take ownership of the growing HIV problem, outside efforts will continue to fail. In some EECA nations, leaders are in denial that HIV/AIDS even exist in their countries – typifying the difficulties that stand between an increasing epidemic and effective solutions.

On top of government inaction and denial, several avenues of international support are not available as policy enticements since median incomes disqualify funding and assistant for many EECA countries – incomes that are by no means truly prosperous. Traditional and orthodox populations in rights-limited societies add to the slow demand for and pace of change. Communication and the free flow of HIV-related information are limited, and a lack of historical commitment to Russian language-based prevention and treatment programs is recognized as a problem for much of the EECA region.

The eastern view from Amsterdam is gloomy but there are glimmers of light. AIDS 2018 will lead to critical analysis of potential solutions for the epidemic in the EECA. Having hit the ground running on this 19^th Day of July, 2018, we hope for an effective conference. If the welcome provided at Amsterdam’s Schiphol Airport to conference participants is any sign, maybe this IAC will come closer to meeting its goals than previous conferences. The response to this epidemic is constrained by resources and shaped by priorities, funding and discrimination and always will be. It is disappointing, for example, that there are no sessions on the impact of HIV on war veterans around the world who suffer disproportionately. The IAS community does not even recognize HIV veterans as a key population group for study and focus. While different, this is reminiscent of AIDS 2017’s lack of programmatic flexibility and basic resolve to act on the dire circumstances in Venezuela, discussed above, when we assembled in Paris.

AIDS 2018 in Amsterdam has an opportunity for real success. The next week will test us all, and we remain cautiously hopeful.

This article originally appeared in

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,

The Conference on Retroviruses and Opportunistic Infections (CROI) provides an annual snapshot of the year’s most interesting and progressive data on HIV cure and remission research. Here’s a quick run down of some of the highlights presented at this year’s conference.

Kick and Kill “Kick and kill” is a strategy that proposes to wake up or activate and then eliminate cells that are latently infected with HIV. Active replication allows the immune system to recognize these cells as a danger, making them a target for therapeutic agents. Researchers evaluated in Rhesus monkeys the combination of GS-9620, a TLR antagonist used to activate latent cells, and PGR121, a broadly neutralizing antibody, to kill off the awakened cells. The monkeys had been virally suppressed for two years. ARVs were discontinued before beginning the dual therapy. Viral suppression was maintained for over three months with this combination. At least half the monkeys remained suppressed at six months. In some cases, the virus remerged but the monkeys’ immune systems were able to re-suppress the virus without the need for additional doses. Additionally, researchers found that, even after viral rebound, the virus was at a lower level (viral setpoint) than it had originally been before the monkeys were given the combo, and the monkeys had lower viral DNA levels in their lymph nodes. This study suggests that the duo may have depleted viral reservoirs and allowed for some level of immune control of the virus.

More Validation of U=U A study relevant to our understanding of viral reservoirs set out to determine if HIV replication occurs in lymph nodes in the presence of viral suppression. Its results are also important to our understanding of the U=U (undetectable equals untransmissable) premise. It has been conclusively established that when a person is undetectable and on sustained treatment for at least six months, he or she can’t transmit HIV to someone else. However, there remains a question as to whether HIV replication occurs elsewhere in the body, such as the lymph nodes, despite it not occurring in the blood, or if ongoing replication in a virally suppressed person stemmed solely from activated latent HIV in viral reservoirs. In this study, Dr. Mary Kearney of NIH’s National Cancer Institute found no evidence of ongoing HIV replication in the lymph node. This study contradicts a previous study published in 2016 that found that HIV replicates in the lymph nodes, helping to replenish viral reservoirs.

CD32+ as a Biomarker? A major barrier to curing HIV is determining which cells harbor latent HIV. Biomarkers are needed to distinguish latently infected cells from cells not harboring the virus. CD32+ was recently suggested as a biomarker to differentiate the two in CD4 cells. Several studies evaluated this hypothesis and determined CD32+ did not identify latently infected reservoir cells. Studies continue to evaluate other surface markers that can be used as biomarkers, allowing researchers to target these cells.

Early ART in Infants The “Mississippi baby” first made us aware that very early treatment with ARVs in infants could produce viral suppression for prolonged periods of time. Several studies were conducted to explore the effects of early initiation of ARVs in infants, two of which were reported at CROI 2018. Both studies found that beginning ARVs shortly after birth was safe, feasible and lead to smaller viral reservoirs.

The first study was conducted in Thailand and compared babies aged four to twenty-three weeks who received uninterrupted triple prophylactic ARV therapy since birth and those who did not receive uninterrupted prophylactic ARV therapy. The study also examined virally suppressed babies, with a median age of 2.7 years, who had initiated prophylactic ARV therapy at or after birth. Evaluating markers of HIV persistence, researchers found the infants who received continuous therapy had significantly lower viral loads and lower levels of integrated DNA, than those who didn’t receive continuous therapy. Also lower were the frequency of latently infected cells and the frequencies of cells producing msRNA spontaneously and after stimulation. In the older babies, after ART initiation, those who had started ARVs at birth had significantly lower total and integrated HIV DNA than children starting treatment later and the size of the inducible reservoir correlated with the age at which they began continuous therapy.

In the second study, infants in Botswana were given antiretroviral therapy before the age of seven days old. They were compared to children who started therapy later. Researchers set out to measure immune responses and discover if early treatment limits the size of viral reservoirs and measure immune responses. They found that those treated within seven days had lower viral reservoirs both at the beginning of the study and after eighty-four weeks. Five of the six children who initiated therapy with the first week of life had a negative qualitative HIV DNA PCR and a negative HIV ELISA test after eighty-six weeks.

Originally published on PanAware on Wordpress.com on May 30, 2018. By Jeannie Wraight.

A Second Berlin Patient? Several attempts have been made in HIV-positive cancer patients to reproduce the possible eradication of HIV seen in Timothy Ray Brown. There have been past reports of procedures that appeared promising, but eventually viral rebound occurred or the patient succumbed to cancer.

During CROI, researchers in Germany reported the case of a forty-one-year-old man in Düsseldorf who continues to show signs, after 900 days, that HIV may have been eradicated from his body.

HIV-positive since November 2010, the unidentified man was diagnosed with acute myeloid leukemia. Doctors attempted to cure him of both his cancer and HIV with the allogenic (involving cells that are genetically dissimilar and hence immunologically incompatible) transplantation of cells from an individual who possessed the CCR5 delta-32 deletion.

To date no HIV proviral DNA has been found in peripheral blood mononuclear cells, bone marrow, or rectal tissue. HIV-specific antibody responses measured by Western blot are waning.

Even in Timothy’s case, eight years later, there still remains an uncertainty as to whether HIV has been completely eradicated from his body. It certainly is too early to label this case an eradication cure and, as the man is still on ARVs, we can’t call this a functional cure. However, the Düsseldorf man appears to be the most promising case to date similar to Timothy Ray Brown.

Post-Treatment Control Results were presented on a subset of participants from the SPARTAC study who experienced post-treatment control after discontinuing ARVs. The SPARTAC study aimed to identify biomarkers that would indicate post treatment control.

Continued follow-up of 3.5 years identified five African participants who continue to maintain viral loads below 400 copies after discontinuation of ARVs. However, two of the five had undetectable viral loads prior to beginning ARVs, which may indicate that they were elite or viremic controllers.

Previous data from the study found three pre-therapy measurements of T-cell exhaustion biomarkers (PD-1, Tim-3 and Lag-3) that were associated with time to viral rebound. However, they did not appear to be significant in the remaining three Africans though it’s difficult to be sure due to the small sample size.

Use of ATI in Curative Studies An abstract entitled “Relationship among viral load outcomes in HIV treatment interruption trials” examined the relation between the time to viral load rebound and analytic treatment interruption (ATI) viral set points.

ATI is thought to be the most conclusive means of studying potential cure strategies in clinical trials. A review was conducted in 235 study participants engaged in six AIDS Clinical Trials Groups (ACTG) studies to gain a better understanding of the relationship between viral rebound (VL) and ATI viral set points. Researchers found:

• Overall, viral rebound and ATI viral set points were associated with time to viral rebound.

• There was no significant association between rebound timing and ATI VL set point for those who rebounded in less than twelve weeks.

• VL set points were lower in participants with rebound over twelve weeks and participants treated during early infection.

• Pre-ART VL correlated with set point, though sixty-eight percent of participants had a set point lower than pre-ART VL.

According to researchers, “[t]hese results illustrate complex relationships between post-ATI virologic outcomes and the potential presence of biological factors mediating rebound timing and set point.”

Immunotherapy to Block PD-1 Researchers led by Rama Rao Amara at The Yerks National Primate Research Center and Emory University developed an antibody intended to block the PD-1 molecule in monkey’s infected with SIV. The anti-PD-1 antibody was studied in conjunction with ARVs to determine if it could flush HIV out of viral reservoirs.

PD-1 is a molecule that inhibits immune response during chronic HIV infection. Antibodies that block PD-1 have been shown to restore T-cell function.

A cohort of monkeys was treated with the anti-PD-1 antibody for fourteen days. After the first ten days of treatment, ARVs were added. This cohort exhibited quicker viral suppression than the control group, with an average time to viral suppression of forty-two days verses 140 days in the control group. More active antiviral T cells were seen in the antibody cohort.

Monkeys in a separate cohort who received the antibody in three infusions, with a month between each infusion, experienced very low levels of SIV. Viral rebounds were reported as short-lived.

The researchers concluded: “These results reveal for the first time the potential of PD-1 blockade, both on restoring anti-viral CD8 T cell function, and possibly destabilizing the viral reservoir under ART. They highlight the potential of PD-1 blockade to work synergistically with other therapeutic agents such as vaccines and latency reversing agents to effectively diminish HIV reservoir under ART as a means to establish a functional cure.”

by Jeannie Wraight

Originally published on PanAware on Wordpress.com on July 1, 2016. By Jeannie Wraight.