They say it takes a village to raise a child. I would also say: It takes a village to support an elder.
I made this remark at a lecture on HIV and aging that I gave in New Orleans last year, sponsored by Merck, in conjunction with the United States Conference on AIDS. The audience consisted of about a hundred AIDS care professionals, mostly physicians, nurse practitioners, and pharmacists, in addition to case managers and patient educators.
I have to confess that I somewhat dread lectures on HIV and aging—both hearing them and giving them. In the past few years, those of us working in HIV care and research and our patients have spent increasing amounts of time talking about this subject. Every time you turn around, it seems, there’s another lecture or webinar about it, almost to the point I feel we hardly talk about anything else anymore.
On one hand, it’s a definite privilege that we get to worry about aging with HIV, given where we were even 15 years ago. That doesn’t allay our simultaneous concerns, however, about the special challenges we’ll confront as adults living with HIV enter their “golden years.” Maintaining the health and good function of aging adults—all adults—is a topic of active study, and we’ve barely begun to understand it. That goes double for the special case of adults also burdened with chronic HIV infection.
Those of us working as health care providers of adults already can see over the horizon the “grey tsunami” approaching, as the Baby Boomer generation gets within a hand’s reach of age 70 and beyond. We worry about the declining ability of our patients to care for themselves, and we worry about our ability to anticipate problems for these patients well enough to prevent medical catastrophe.
I would say, however, that as a former ACT UP’er who later became an AIDS researcher and HIV physician, my experience when facing seemingly overwhelming or unsolvable problems is that what seems impossible when faced alone becomes possible when faced with a community at your back. Much of what the AIDS community has accomplished in our 30-plus year history seems in hindsight quite remarkable. Activists dispatched problems of medicine, science, and policy again and again, working together. I remain optimistic that this same approach will pay off in meeting the latest set of challenges of aging HIV-positive adults, and this is the message I have strived to bring to audiences when I speak on the topic.
The generalities of the issue of HIV and aging came into sharp personal focus for me in the past five years, as I now live in the retirement community of the Coachella Valley, in Southern California. I work in a large medical group practice in Palm Springs, and my particular office caters mainly to the aging LGBT patient population, many of whom are also living with HIV.
I came to the valley almost five years ago to take a job helping create a new internal medicine residency at Eisenhower Medical Center. Eisenhower is one of the two largest hospitals in the region and the first to have any kind of academic medicine program. That, too, has brought with it its own set of challenges. But it did not take long for me to realize the special opportunities such a place offers to medical researchers interested in the problems of “successful aging”—again, both in the general adult population and in those living with HIV.
In the article below, I will outline the nature of the problem posed by aging successfully with HIV, and then talk about how I and my research collaborators here in the Coachella Valley are taking advantage of the increasing numbers of HIV-positive adults living in the area to launch a project aimed at gaining insight into their special needs. Our hope, of course, is that the lessons we learn will assist service agencies and policy makers worldwide in better addressing the needs of our patient community.
“I have to deal with the reality.”
–Project GRACIE focus group participant
In the developed world, the face of HIV infection is growing older. Most of us have heard the statistic that by 2015, 50% of all HIV-positive adults in the U.S. will be over the age of 50. Going along with this trend, HIV patients today are not only living with HIV, but with the “diseases of aging.” As people with HIV enter their 60s, more than half of them will demonstrate hypertension and high cholesterol. Nearly 20% will have documented coronary artery disease, the condition that gives rise to heart attacks; over 25% will have kidney disease and a similar number will have confirmed diabetes.
There are some special issues with HIV-positive adults dealing with other chronic medical conditions. For one, compared to their HIV-negative peers, adults living with HIV seem to be more likely to be dealing with more than one chronic medical condition at a time. In one study in veterans, for example, people living with HIV who were 50 years of age or older were much more likely to have multiple other chronic illnesses compared with their age-matched HIV-negative peers. For adults with HIV age 60 or older, the vast majority—70%—had at least one other chronic medical problem. Coronary artery disease, at least until people reach their 70s, seems to be roughly three times more prevalent in HIV-positive adults compared to HIV-negative people of the same age, even when corrected for the presence of other risk factors such as smoking or obesity.
Besides the high rate of kidney disease previously mentioned, patients also have a high rate of liver disease—often due to co-infection with hepatitis B or hepatitis C. Rates of bone density loss—osteopenia and osteoporosis—are much higher in HIV-positive adults when compared to HIV negative adults, and unsurprisingly, the rate of bone fractures is 50% higher.
Perhaps most worrisome to my audiences of HIV-positive adults is the higher rate of memory impairment and development of early dementia we are seeing. Even HIV-positive adults with no other HIV-related symptoms will more commonly experience a decline in brain function. One study found that the rate is nearly twice as high, with at least mild cognitive impairment—problems with thinking or memory—being found in 36% of HIV-positive adults, compared with 16% in HIV-negative people of the same age.
The neurocognitive issues of HIV-infected adults is a special research interest of our collaborators from UC San Diego, Drs. Ronald Ellis and David Moore, and we have been assisting them in reaching more elderly HIV-positive adults living in the valley for their important work in this area.
Not only do people with HIV contend with more medical problems compared to their HIV-negative peers, they also seem to have a rougher time with the conditions they do have. One of the most striking studies speaking to this was conducted by Kris Ann Oursler, a gerontologist at the University of Maryland with an interest in HIV-positive adults. Her project, analyzing health outcomes in veterans, found that patients’ function in daily activities, as assessed by patients themselves, declined three times faster in HIV-positive adults compared to their HIV-negative peers living with the same conditions.
For example, for a person who had chronic obstructive lung disease (COPD, sometimes known to laypersons as “smoker’s lungs”), his or her ability to manage daily tasks affected by that condition, such as limited walking due to shortness of breath, got worse over time at a faster rate if the person also had HIV infection.
What drives the higher number and severity of chronic medical conditions in HIV-positive adults? It has been hypothesized that HIV may hyper-stimulate the immune system, producing chronic inflammation. “Inflammation” is familiar to anyone who’s had a splinter. The area around the splinter may get red, hot, and swollen; all of these are physical signs of an active immune system “fighting” the foreign invader—in this case, the piece of wood.
These immune activities in the short term may help fight off a challenge to the body, such as an infection. But, if inflammation persists for days, months, or years, it can take a toll on the body. Imagine you are cooking at home, and the food in the frying pan starts to burn. The smoke alarm goes off, you pull the pan off the stove, and a fire is prevented. On the other hand, if the smoke alarm never shuts off, it would really start to make the cook feel frazzled. Like a smoke alarm that won’t shut up, inflammation that never shuts off can turn from the body’s friend into its foe.
One important study that gave us insight into the chronic inflammation of HIV-infection was the SMART study, which looked at HIV-positive adults using HIV medications. The study compared patients who stayed on their medicines consistently to those who took breaks from their medicines from time to time (what we call “drug holidays” or “treatment interruptions”). The big lesson of the study was that taking breaks from medication actually produced much worse outcomes for the patients than staying on medicines consistently from day to day.
In the SMART study, patients with HIV infection who were treated using a CD4 count-guided “drug conservation” approach had significantly greater all-cause mortality than those treated for maximal viral suppression. The role of inflammatory and coagulation biomarkers in mortality in this population has subsequently been studied.
Older adults participating in the SMART study, compared with adults from two large general population studies, had significant elevations in markers of inflammatory (hsCRP and IL-6), coagulation, and fibrinolysis activity (D-dimer), as well as renal function impairment (cystatin-C).
Besides the medical issues, there are social factors that distinguish HIV-positive adults that concern me as a primary care provider who takes care of them. I consider social isolation—living alone, and/or having fewer family or friends around to offer help when needed—to be a dangerous risk factor for poor medical outcomes in my patients, and when I see that, I try to get these patients enrolled in programs that bring volunteers or other help into the home. While it varies from person to person, the literature shows that on average, older HIV-positive adults tend to be more socially isolated than their younger counterparts. Older people with HIV are also more likely to live alone. This may also contribute to their challenges in successfully meeting the challenges of aging.
“We are an open book.”
–Project GRACIE focus group participant
Southern California’s Coachella Valley and Inland Empire are home to one of the largest groups of long-term survivors of HIV infection to be found anywhere in the world. As a retirement community, Palm Springs has been a traditional magnet for LGBT vacationers, and often as these adults approach retirement age, they make their stays here longer and longer until they become year-round residents. Many of these people are living with HIV.
In the past five years, the number of doctors and nurses trained in HIV care living here has greatly increased in order to meet the special needs of this group of individuals. As noted above, these patients struggle with the insidious effects of chronic HIV infection and co-morbid diseases of aging, as well as from the side effects of long-term multi-drug antiretroviral therapy.
In the past year, I and my research team, including Drs. Gerry Bocian and Carlos Martinez, and research assistant Erik Hernandez, have been meeting monthly with clinician-scientists working at other HIV care centers around the valley. Our colleagues include Dr. Clayton Barbour, nurse practitioner Joseph Dahman, and nurse Chuck Marbley, all from Borrego Community Health Foundation; Dr. Shubha Kerkar, a founding physician of the Desert AIDS Project (DAP) and main HIV provider at Desert Oasis HMO; and Dr. Steven Scheibel, the medical director of DAP. The purpose of our meetings was to discuss common concerns regarding our care and research work here.
At one of our meetings in early 2014, our aforementioned UCSD colleagues Drs. Ron Ellis and David Moore presented a summary of recent cohort studies of HIV-positive adults. They noted that the number of adults age 65 or older, in total, across about a dozen studies combined, numbered no more than about two dozen individuals. In my own panel, it is the group of adults under the age of 50 that I can count on two hands—most of my HIV patients are significantly older. The pattern is the same for the other local HIV providers.
After discussion, we agreed that we had a unique opportunity here—indeed, a responsibility—to take advantage of this concentration of adults aging with HIV to better understand their health and care needs. Thus, we created plans for Project GRACIE (Geriatric Research of AIDS Comorbidities in the Inland Empire), a prospective cohort study of HIV-positive adults aged 50 or older, as well as HIV-negative, aged-matched peers.
The purpose of Project GRACIE is to rectify the absence of information on HIV-positive elders and their specific aging-related challenges by enrolling up to 300 individuals, all over age 50, in a decade-long, prospective study that will provide the scientific, pharmaceutical, and medical communities with an accurate, detailed, data-rich portrait of aging AIDS patients—and provide clear guidelines for the optimal medical management of older, seropositive individuals.
Project GRACIE’s approach is informed by some of the specific challenges posed by our situation in the valley—and I think our roots in the activism of the AIDS movement will help us. For starters, aside from our relationship with our colleagues at UCSD, we have no major medical university program as a base; rather, we will be doing this research work “in the community.” Fortunately, the AIDS movement practically invented “community-based research,” starting with the Community Research Initiative on AIDS (now known as ACRIA) in New York, co-founded by my former mentor, Dr. Joseph Sonnabend, and its San Francisco counterpart, the Community Consortium, led by another of my mentors, Dr. Donald Abrams. Both organizations pioneered the implementation of cutting-edge basic and clinical research conducted in the office of AIDS primary care providers, outside a university setting, in the early 1990s.
Community-based research doesn’t simply mean doing research work outside a university. It also connotes a partnership with the patients, informed by feedback on their needs and concerns.
I am hoping, along with my Coachella Valley colleagues, to instill in our future work the same kind of partnering with patient volunteers in our research that I witnessed in many UCSF projects in San Francisco. I had the good fortune in the mid-1990s to work with Dr. Mike McCune’s lab at the Gladstone Institute of Virology and Immunology (GIVI) at UCSF. There, I watched his team of scientists benefit “at the bench side” from an ongoing dialogue with patients and activists who contributed to the development of their studies and supported their success. I also helped Dr. Steven Deeks create the SCOPE cohort—now a large, NIH-supported prospective study based at San Francisco General Hospital—and watched the development of the OPTIONS early HIV infection cohort study there. Both projects exemplified similar active partnership with the patient volunteers. It was part of the work culture of the clinician-scientists at our labs to see patients as active members of the research team, contributing in the most personal way possible—with their bodies. But patients also helped by giving us their ideas, observation, and feedback, and their willingness to let their primary care providers and the larger patient community know about our work. We hope to establish a similar culture of partnership with Project GRACIE.
“Take what you need and what you want, because essentially you need this information from us.”
–Project GRACIE focus group participant
To get GRACIE off on the right foot, we have been conducting focus groups with HIV-positive adults age 55 or older, to get their direct feedback about what their concerns would be in participating in such a project. This will allow us to anticipate the concerns of our volunteers and address them right from the start of the project. I think we will have the support of the community.
And, we will need it. Establishing a prospective cohort study in a community setting is no mean feat. It will require significant organizational support, which translates into a need for expertise and finances. We attempt it at a time when NIH funding for all medical research has been declining steadily every year for the past decade. It feels like climbing a mountain.
Fortunately, when one climbs Mount Everest, one goes up the icy slopes with a band of fellow mountaineers. And, with Project GRACIE, so far, every time I thought we were licked and couldn’t surmount the next challenge, people came out of the woodwork to help us. We have been helped by our local activists, including Jeff Taylor and Jonathan Goldman, who’ve been running our focus groups; Marlene Estevez, a local pre-medical student and the main administrator of the nascent project; Edwin “Ned” Bayrd, formerly of the UCLA AIDS Institute, whose operational savvy has been hugely helpful; and many others. It is the contributions of these additional people that have allowed our science team to continue to push forward, step by step.
Funding for GRACIE will be a creative challenge. As I mentioned, NIH funding continues to drop for projects like this. We’ve been in touch with Dr. Kenneth Lichtenstein of the HOPS HIV cohort study—a famous study somewhat similar in nature to what we envision for GRACIE—who has given us some ideas of ways to add to our infrastructure without adding to our explicit expenses. Many of the AIDS-care and medical organizations in our region—including my own hospital—have supported their operations with private donations, and we will likely proceed in a similar fashion. Likewise, so far our GRACIE focus group participants have commented that they do not have a problem with us getting financial support from pharmaceutical industry sources, so long as the GRACIE team—researchers and participants—controls the research agenda. And, as I mentioned, all of what we’ve accomplished to date has happened thanks to volunteers.
“It would be nice to be asked if I need to talk to someone. A lot of these trials bring up emotional history.”
–Project GRACIE focus group participant
The next step in our work—what we’ve dubbed “Phase 0”—will be a planned chart review project, which will be handled by a four-person team of resident doctors, working under each of our principal investigators at their individual clinic locations. The purpose of this phase will be to characterize the comorbid medical problems of older HIV patients, and compare those findings to the established medical literature. This part was formally announced December 1, 2014, World AIDS Day. The nice part about a chart review project is that its financial burdens are quite modest.
The next phase would include, in addition to surveys of the patient-participants, collecting and storing blood and tissue samples taken from volunteers. The objective of this phase of Project GRACIE will be to monitor, quantify, and compare the comorbidities seen in older individuals living with HIV to those in age-matched sero-negative controls. A number of clinical markers of disease, including some of the inflammatory markers mentioned above, will be monitored in this work.
It has been interesting to me that the focus group members have commented that getting support for coping with the challenges of aging doesn’t simply mean studying the problems. While they recognize the need to involve the pharmaceutical industry as partners in supporting this work, they also wanted to make sure the investigators think about complementary therapies, including nutrition and modalities like acupuncture, in the therapeutic studies that will likely unfold out of the GRACIE project. Likewise, I anticipate that GRACIE will partner with some of our local care agencies to make sure our participants will take advantage of the existing support resources in the valley, even as our research helps shape and mold those resources for even better support in the future.
So, it takes a village. In surmounting the challenges of AIDS, it always has, and probably always will. Project GRACIE will move forward thanks to the support of many scientists, care providers, and advocates, but most importantly, the community of aging HIV-positive adults living here in the valley. I hope what we learn will benefit the larger world community of people living with HIV/AIDS and care providers.
Rick Loftus, MD, is an Associate Program Director of the Internal Medicine Residency Program at Eisenhower Medical Center in Rancho Mirage, California, and an Adjunct Clinical Assistant Professor of Medicine at the Keck School of Medicine of the University of Southern California. He would like to acknowledge Project GRACIE volunteers Edwin “Ned” Baird and Marlene Estevez for assistance in creating this article. He can be reached at rloftus@emc.org.