The 16th Annual International Workshop on Aging and HIV was held in Washington DC on October 23rd and 24th this year. This annual gathering is one of my favorite conferences of the year for what it is as well as what it is not. It is a gathering of young, early career HIV researchers and their mentors providing unique insight into what issues the next generation sees as important areas on which to focus. It is not another huge conference with thousands of people and complex schedules that make it difficult to focus on what is being presented. This conference occurs in a single room where all participants hear every presentation, so everyone participates in every discussion.

In past years at this (and every other) conference the focus is often on the pure scientific work being done and the sometimes esoteric results observed. Relatively little time is given to the practical implications of the work for those of us living and aging with HIV. This has spurred me to ask the question, “So What?” in the Q&A following may presentations, trying to get some focus on how the often interesting scientific work will translate into some benefit for an increasingly aging HIV+ population in time to make a difference in our lives. This year's workshop did a good job of balancing perspectives and at least this group of researchers appears to have heard and internalized that message. In addition to the great science presented, there was lots of focus on application, new diagnostic approaches and care models.

So let’s take a look at what I thought were the key learning from this week; (Once the slides are published I’ll try and include more of those where it makes sense)

Sensory Impairment and Cognition

The first block of presentations were focused on the impact of sensory impairment on cognition. This was divided into presentations on the impact of sight, hearing, smell and pain on frailty and cognition. The common thread through each of the discussions was a lack of clarity on whether the impact on these senses was primarily due to the impact of HIV or due to normal aging-related changes. My sense of the discussions is that while PLWH certainly are impacted by aging related changes, HIV tends to accelerate the onset of issues. Monitoring these changes can be used in a diagnostic capacity to predict disease progression and the onset of other related conditions as well as frailty.

In the discussion on vision and hearing from Allison Abraham, it was noted that 80% of vision changes are correctable, 20% of the remainder were related to cataracts. The prevalence of difficulties was 5% greater in PLWH. Hearing changes were progressive and it was unclear if the cause was aging or HIV. It was noted that vanity often plays a role in hearing aid avoidance sometimes delaying the use of assistive devices that may be perceived as a sign of age. With the advent of over the counter hearing aids such as apple earpods, there was a discussion on whether insurance played a role in ensuring access.

The next presentation by David Moore was on olfaction (smell). The top 3 causes of changes in the sense of small are aging, neurodegenerative disease and viral illnesses. The long term impact of COVD is still unclear but this viral illness is responsible for an increased number of casses of reduces of loss of the sense of smell. There are, unfortunately, no really effective corrective treatments. Olfactory impairment is an early sign of Alzheimer's prior to cognitive impairment and testing this may be a good diagnostic tool to predict cognitive impairment. Poorer smell relates to poorer recall and cognition among PLWH above age 60.

The final presentation in this section from Jessica Robinson was on pain, defined as an unpleasant sensory or emotional experience. There are many causes of pain, no approved treatment related to HIV. When considering treatment for chronic pain, it is important to set realistic goals as freedom from pain is an unlikely outcome. A number of approaches, often combining psychological (Attitude) and pharmaceutical management approaches are being studied. Cannabis can be effective, although legality varies by state.

In the Q&A, there was discussion of the impact of polypharmacy as an underlying cause as people look for solutions, particularly to chronic pain. How to manage opioid sparing regimens was another topic although no conclusions other than a need to manage this. A recurring theme throughout the day was first brought into this discussion regarding methods for managing the need to involve multiple specialties in the treatment of patients. What is the optimal model of care in cases where PLWH have many ongoing conditions.

This section had a great combination of scientific data regarding sensory impairment and treatment as well as the potential for using these impairments as diagnostic tools in PLWH to detect early onset of frailty and neurocognitive impairment.

Impact of Chronic Inflammation in the Aging Population

The presentations in this section focused on the impact and factors related to chronic inflammation in aging PLWH. While my perception of this discussion was more aligned to the pure science side of things, I found the information to be valuable and a likely precursor to some later intervention and diagnostic approaches.

The first presentation, from Caroline Foster, focused on the impact of chronic inflammation in the perinatally exposed population, otherwise referred to as Dandelions or those born with HIV. In all PLWH there is some amount of background inflammation and viral replication even in the presence of effective ART. PLWH who were HIV+ prior to the advent of truly effective ART is the mid 1990s experienced more significant impact from the ongoing infection and inflammatory response and are unlikely to ever fully recover to a normal CD4 T cell population nor a healthy CD4/CD8 percentage and are therefore more likely to be susceptible to later infections. Those who started on ART early and achieved undetectable viral loads and near normal CD4 rebound are still affected by the effects of background inflammation leading to premature onset of aging related conditions. These effects are seen at a much earlier age in the prenatally infected population, as they have the same level of exposure as a 60 year old infected in their late 20s or early 30s. The onset of aging related conditions may therefore begin to appear while there people are in their 30s, leading to a shorter than normal lifespan. Even with lifelong ART, cardio, respiratory, renal amd neuro decline is prevalent.

The next discussion, from Peter Hunt, built on the observation that PLWH have higher aging related mobility and mortality than the general population despite suppressive ART due to persistent inflammation. He highlighted the association of the onset of frailty in the PLWH population to the presence of ongoing background inflammation. CMV infection is also associated with immunosenescence. Immunosenescence refers to the age-related decline in the function and effectiveness of the immune system. As individuals age, their immune system gradually weakens, making them more susceptible to infections, autoimmune disorders, and other health problems. As most of the population is co-infected with CMV, the presence of this and other co-infections contributes to the amount of inflammatory response. There is some evidence that treating CMV 9or possibly other co-infections, may reduce the speed of decline in PLWH.

Sean Leng built on this discussion by looking at the impact of ART on CMV IgG. A positive CMV IgG test result means that the person has been infected with CMV at some point in their life. ART based HIV suppression can reduce CMV inflammation impact to aging related diseases. Regardless of when a person seroconverted, the prevalence of CMV IgG decreased dramatically once suppressed. For me, this raised a number of questions about the need for and impact of treatment of co-existing conditions and the models of care that bring together specialists in multiple disciplines to work together. These discussions also raised questions for me abou thte impact of a cure study sponsored by UCSD and th eCity of Hope using CMV CAR-T cells to target HIV in the viral reservoirs. The UCSD folks present weren’t familiar enough with this to have an opinion, but I will follow up. https://idgph.ucsd.edu/research/avrc/participate/cmv-hiv-car-tcell.html

Industry Symposium - Starting Early: Preventive Strategies to Minimize Aging related Co-morbidities in Older PLWH

The next section was a discussion of strategies to address the aging related conditions and comorbidities common among PLWH and strategies to address them. Up to this point in the presentations, the topics have been related to the reasons why aging is often accelerated in PLWH and this group of presenters started to address ways to offset those impacts.

Julian Falutz began by addressing the differences between biological and chronological aging and the impact of each on HIV. Chronological age is simple, its the length of time a person has been alive. Biologic, or epigenetic age refers to the biological age of a person’s cells, tissues and organ systems. If an individual’s epigenetic age is greater than their chronological age, the person is undergoing epigenetic age acceleration, which is associated with higher risk of cancer, cardiovascular disease, Parkinson’s disease and other diseases. Based on four different epigenetic “clocks” that measure biological aging, every five to eight years of epigenetic age acceleration was associated with 20 percent to 32 percent lower odds of living to age 90 with intact mobility and cognitive function. Biologic age is multifaceted and influenced by genetics and lifestyle factors and can predict health outcomes and mortality better than just chronologic age. Biologic age accelerates pre art and slows post art but never returns to pre-hiv levels. Acceleration of biologic age appears to be slower in women. Age acceleration may contribute to early aging related comorbidities and geriatric syndromes.

Venessa Johnson then discussed the impact of obesity on aging related comorbidities, especially in black women. Some 50% of black women with HIV are obese. Of women who died with HIV in 2022, 57% were black women. This is due to a number of factors, including stigma, late diagnosis or access to and retention in care, cultural economic or psychological issues.

Tristan Barber went on to describe various strategies and clinical interventions that can impact biologic age and the onset of age related and geriatric symptoms. Frailty is NOT permanent, it can be positively impacted. The key strategy is to improve physical function and nutrition as well as improving psychological status or quality of life.her key strategy is to have geriatricians participate in medication reviews. Polypharmacy is a big problem as we age as medications are added but rarely stopped. The effects of some medications on older folks can also change and become more or less effective and may also be impacted by combinations of therapies. An Annual review by the care team is crucial. From a pharmaceutical perspective, GLP-1, Metformin, anti-inflammatories are some of the key therapies that can reduce the impact or delay onset of frailty. The most impactful thing that a PLWH can do to delay or reverse frailty is EXERCISE, and this does include sexual activity.

Glucose Metabolism and Exercise

The final block of presentation on the first day focused on the erole of changes in the way the body processes glucose, pharmacological interventions and the impact of exercise on frailty and overall health.

Todd Brown gave a great presentation on the impact of GLP-1 agonists (Ozempic and related drugs). While the news may be promising for those aging with HIV, the results are neither clear nor necessarily all beneficial and this should only be undertaken under supervision of a physician who is familiar and following this rapidly evolving research area. Possible long term effects include a reduction in Cardiovascular Disease (CVD), preservation of renal function and positive kidney impact related to MASH and Chronic kidney disease. There may be a positive correlation to improvements in neurocognitive function. Possible risks are unclear. The loss of muscle mass in addition to fat loss is also seen, particularly in PLWH over the age of 60. Even though muscle mass is reduced, muscle function (Strength) is not reduced. Impacts (loss) in bone density are also seen leading to a possible increase in fracture risk. Exercise and Liraglutide have the greatest impact of weight loss in combination. a 30% loss in visceral fat has also been shown in PLWH, which may improve epigenetic markers for biological aging. OVerall though, the impact of GLP-1 agonist on aging is still inconclusive but is an area certainly to watch.

Kristine Erlandson continues the excellent work on the impact of exercise on PLWH. We have reported on past events that her team found that PLWH showed significant response to exercise in improvement or delayed onset of aging related comorbidities, particularly with High Intensity Interval Training (HIIT). Many folks have expressed concern over the difficulty as we age in engaging in this aggressive level of activity. The study reported this year compared HIIT to a more moderate level of activity and found that while HIIT provided the greatest benefit, moderate exercise achieved significant improvement almost to the same level. PLWH achieved similar or greater improvement in function with exercise. Those with increased inflammation tended to respond less well with a lower improvement in cardiovascular response.

One of the observations from past studies was that people tended to stop or reduce their level of activity once the study exercise visits had ended. They experimented with multiple approaches and found that personalized text messages and reminders had the greatest influence on folks continuing to exercise until it became a habit. Group workouts, while effective in enhancing participation, were very difficult to manage in a study environment due to personal scheduling conflicts and other reasons. (We found the same effect with the NeXT program, so have moved to a non-study approach). When comparing various types of exercise, the combination of light cardio with resistance training had the greatest impact. Tai-Chi also showed good response, yoga only minimal response (which makes sense given the levels of strenuous activity involved)

NOTE: It is studies such as this that led to the creation and POZabilities focus on exercise and nutrition in our Healthy Living programs. In combination with good medical care for HIV and comorbidities this and other studies regularly show that exercise and good nutrition can do more to help keep us healthy with better Quality of Life longer.

Arman Khan reported that aging shows an increase in visceral fat along with depletion of subcutaneous fat deposits. The use of ART may lead to a loss in the density of adipose (Fat). This lower density may contribute to an increase in insulin resistance. PLWH show an acceleration of these changes in tissue density. This highlighted for me the potential benefits of the use of GLP-1 agonists in PLHW, although more information is needed to address some of the negative impacts of these drugs.

Abstract Driven Presentations

There were a number of great study abstracts made available either as posters, presentation or both. Ill summarize a few of them here or show picture of the posters.

Javana Milic presented on the use of AI to help address polypharmacy issues. Patients were asked to scan prescription bar codes and dosage info, a physician then checks against what was prescribed. The AI checks against NavPharma database for interactions, the results are sent to a pharmacist for review. Recommendations are generated and any changes discussed with the patient and updates in patient prescriptions and records made. The study found meds prescribed but not taken(28%), meds taken not prescribed, started some new and desprescribed (11%).

Vitor Oliviera (a physical therapist and trainer) described additional results from the HIIT vs moderate exercise regimen studies. For frailty and sarcopenia (age-related loss of muscle mass and strength) no pharmacological treatment exists today, exercise is the primary preventative approach. HIIT provided the most benefit, but moderate exercise regimen provided still significant results. Resistance training was included and the same to both arms. 3 of 5 tested and rated frail at onset improved, 1 HIIT participant was rated no longer frail following the regimen.

Jacob Walker reported on the use of gait speed (time to walk 4 meters at normal pace) to assess the need for further follow up in their clinic for frailty. PLWH appear to show a decline in gait speed earlier than non-HIV patients. The goal of the study was to have clinicians measure gait speed walking down the hallway to treatment rooms for all patients over age 50. Patients with a less than normal (.6 meter/sec) were referred to resources to improve.

Todd Brown reported that PLWH experience a higher rate of fractures than HIV- aging individuals. They checked gait speed and grip strength to measure the impact of the fracture. They observes a steep decline in grip strength following the fracture with a gradual (over 2 years) return to normal. PLWH experiences a steeper decline in strength than HIV-

Here are a few notable abstract posters from the conference:

There were a umber of presentation on models of care througout the conference. I’m not going to cover them in detail, but a few common threads emerged:

Coordination of care is important as we age. We tend to see specialists from a number of disciplines and it is important to coordinate care - ideally in a single visit where practical for evaluation. This can be physical or virtual (telemed).
The inclusion of a gerontologist is key to assessing the impact of aging related conditions in combination with the other specialties
The inclusion of peer led support generally leads to improved outcomes
Screening tools must be simple to use in a clinical setting to assess frailty and neurocognitive impact

Finally, there was a community activist led discussion led by Linda Scruggs of Ribbon. Much of the discussion was about the need for support for community members as they age. The government is not doing enough and the potential break in availability of medicaid, food support and other critical needs will impact the community. All fair comments but not likely to change anything by themselves. There was an activist community member (who looks a lot like me) in the audience who noted a few key points:

The HIV community has a history of activism that forces change. Look at today’s availability of early access and compassionate use protocols in drug development. There were a direct result of early ACT-Up and other groups pushing the government to act.
If we are worried about the pause in food stamps, what are WE doing to address that? Local San Diego groups (Kiwanis, etc) are collecting food for those in need during any gap in funding. It is our responsibility to care for our community.
We are NOT victims unless we allow ourselves to be. The older member of the community need to work with our younger community member to re-learn how to take control of our own destinies and be the catalysts of change.

One further note for the POZabilities community; several of the speakers recognized and noted the work and services provided by POZabilities, particularly the availability of our Healthy Living programs. At least one of the panel participants was “jealous” that we had access to a personal trainer for our folks. Given the clear benefits of exercise to our community in the prevention and treatment of frailty, it’s good to know we are perceived as leaders on the national stage!

Wrapping it up

In summary, this was a great conference that moved the needle a bit away from pure science and into addressing how the science can drive change that add meaningful value into the lives of a rapidly aging population of those living with HIV. Kudos to the organizers for this movement. This conference is being driven in large part by groups of your researchers, who we as older community members need to encourage to act with a sense of urgency to address the needs of an aging population, as well as support the goals of ending the epidemic. Through aggressive treatment of the HIV+ population and the use of PreP and other prevention strategies in the HIV- population we can end or at least reduce the incidence of HIV to the point it is no longer the epidemic it still remains.

Updates from the International Workshop on Aging and HIV