In the 40 years since AIDS was first identified at UCLA, the university has been at the forefront of research and clinical advances that have transformed the disease from an almost-certain death sentence to a treatable chronic illness.
This is Part 2 of a two-part story chronicling UCLA’s engagement with the HIV/AIDS epidemic over the past four decades. Part 1, detailing the first identification of AIDS at UCLA and the efforts that followed to overcome the scientific, clinical and social hurdles of the deadly new illness, appeared in the Fall 2021 issue of U Magazine.
By Dan Gordon
Tom Gillman has lived a long time with AIDS. He was 38 years old when he was diagnosed in 1984. Now he is 75. His journey with AIDS has taken up half of his life, and it has often been filled with obstacles and pain. “In my darkest days, I’ve felt like I was in a rowboat in the middle of a very rough ocean,” he says.
But it also has been a journey punctuated with hope. For that, Gillman credits Ronald T. Mitsuyasu, MD ’78 (FEL ’84), who has managed Gillman’s care for the past 37 years, and the clinical AIDS research and treatment program that Dr. Mitsuyasu founded at UCLA. “There’s no question about it, Dr. Mitsuyasu and his clinic saved my life,” Gillman says.
Dr. Mitsuyasu, a hematologist-oncologist who was starting his fellowship training when the first report of a group of young gay men with an unusual constellation of illnesses was published in 1981, was one of UCLA’s earliest clinicians treating patients with AIDS. The clinic Dr. Mitsuyasu established in 1983 has gone through numerous iterations over the years. Starting in a basement in UCLA’s Center for the Health Sciences to today’s bright and modern suite in a building on Pico Boulevard, where it operates as a multidisciplinary hub of state-of-the-art medical care, clinical trials, education and research, the program now known as the Clinical AIDS Research and Education (CARE) Center remained under his direction until Dr. Mitsuyasu announced his retirement in 2020.
But Dr. Mitsuyasu continued to see patients for a year after retiring, and when Gillman learned that he would be having a final clinic day this past June, he rushed to get on the calendar to be Dr. Mitsuyasu’s last patient.
Their journey together has been extraordinary. Gillman is among the few survivors from those earliest years. “My job has been to stay alive,” Gillman says. “In that regard, I’ve done pretty damn well.” When Gillman first came to the clinic, with a diagnosis of Kaposi’s sarcoma (KI), Dr. Mitsuyasu started him in a study of interferon alpha, one of the first drugs tested for AIDS-related KI. Other trials followed over the years.
“It has been a hell of a journey,” Dr. Mitsuyasu says. That journey has encompassed almost the entirety of the history of AIDS to date, starting with its first identification by a young physician at UCLA 40 years ago. Throughout that time, UCLA has been at the forefront of research and clinical advances that have transformed AIDS from a near-certain death sentence to a treatable chronic illness, akin to diabetes. Gillman is a living example of the progress that has been made.
Judith S. Currier, MD, was in medical school at Dartmouth when UCLA reported the first AIDS cases. She remembers a microbiology professor telling his students about the importance of reading the Morbidity and Mortality Weekly Report of the U.S. Centers for Disease Control and Prevention (CDC) to stay well-informed about the world of infectious diseases. When her professor read the June 5, 1981 MMWR, with its three-page report by a young UCLA immunologist named Michael Gottlieb, MD, and four of his colleagues titled “Pneumocystis Pneumonia — Los Angeles,” he said, “Mark my words, this is going to be something,” Dr. Currier recalls.
In 1985, Dr. Currier moved to Boston for her training; since she was interested in both laboratory immunology and primary care, HIV seemed like the ideal way to combine the two. “We saw a lot of people admitted to the hospital who never got out,” Dr. Currier says. “Without any treatment, we tried to support them the best we could.” But through her involvement with clinical trials, Dr. Currier saw the emergence of medications that helped patients, at least in the short term. That ignited her interest in HIV/AIDS research. She came to Los Angeles in 1993 as medical director of the L.A. County-USC Rand Schrader HIV clinic, then moved to UCLA in 1998 to focus on HIV/ AIDS research — including studies that shed light on the unique health impacts for women living with HIV — and became associate director of the CARE Center.
She serves as the national chair of the AIDS Clinical Trials Group (ACTG), an international network of centers evaluating trials of treatments for HIV, the virus that causes AIDS, and is chief of the UCLA Division of Infectious Diseases. She assumed the role of director of the CARE Center in June 2020. From her vantage, Dr. Currier has had a front-row seat to the dramatic medical advances that have altered the landscape for patients with AIDS. An important breakthrough came in 1996, when research showed that the combination of three antiretroviral medications — the “cocktail” known as highly active antiretroviral therapy (HAART), and now more commonly known as antiretroviral therapy (ART) — could durably suppress the virus to the point that it was no longer detectable. UCLA was a site for many of the pivotal multicenter studies, with investigators whose work informed the treatments.
“It’s been stunning and spectacular to see people going from trying to survive from one birthday to the next to being able to live a full life.” Dr. Currier says. “Many times, it can take decades before scientific findings are translated into something that will impact patients. We’ve had the incredible privilege of moving developments from the laboratory into the clinic over just a few years.” Raphael J. Landovitz, MD, graduated from Harvard Medical School the year antiretroviral therapy changed the paradigm for HIV care. By that time, he had already decided on his career path, based on an experience he had as a third-year medical student helping to provide hospital care for a patient with cerebral toxoplasmosis — a complication of advanced HIV/AIDS. Despite numerous clues of a progressive immunodeficiency, the patient hadn’t been tested for HIV until well into his illness. When Dr. Landovitz asked the man’s primary-care physician why not, the doctor responded disparagingly: “I don’t do AIDS.”
“I was rattled to my core,” Dr. Landovitz recalls. “What does that mean — that it’s too complicated? Or that you don’t want to care for people in the risk groups affected most by HIV? At that moment, I decided I was going to be the best physician who ‘does HIV/AIDS’ that I could be.” Dr. Landovitz was recruited in 2006 to join the UCLA CARE Center, where he now serves as co-director. He entered the field at an inflection point, not only for HIV therapeutics, but also for HIV prevention, his major interest.
He is now a leader in research focusing on preventive approaches such as pre-exposure prophylaxis (PrEP), a daily pill that greatly reduces the risk of acquiring HIV, and post-exposure prophylaxis (PEP), medication that can lower the risk of becoming HIV-positive if started within three days of exposure. “It used to be that all we could offer were behavioral strategies, like ‘use a condom,’” he says. “My arrival at UCLA coincided with an explosion in our understanding of what was possible and opportunities to develop and implement these strategies as part of our prevention tool kit.”
While effective therapy has been a game changer, it by no means has solved all of the problems associated with the HIV/AIDS epidemic. As more patients live longer with the virus, it has become clear that HIV exacerbates the aging process — including an increased risk of heart attack, stroke, neuropathy, certain cancers and dementia — from both the virus and the long-term medications to keep it in check. Beyond that, Dr. Currier says, “One of the biggest challenges is to implement the effective tools we have for both prevention and treatment.”
In 2016, the Joint United Nations Programme on HIV/ AIDS established an ambitious goal for all countries to reach by 2020, known as 90-90-90: 90% of all people with HIV knowing their HIV status, 90% of those who know their HIV-positive status being on antiretroviral therapy and 90% of those receiving antiretroviral therapy experiencing viral suppression. All but 14 countries fell short of the goals, including the United States. In Los Angeles County, Dr. Landovitz notes, the overall number of people living with HIV who don’t know they are infected is 9-to-10%. However, according to the latest statistics, that number is as high as 20-to-40% for some age groups and other high-risk populations. “Until we remove the stigma attached to an HIV diagnosis, we’re never going to encourage people who are most at risk and most disenfranchised from medical interventions to come forward and get tested so that we can move to the next step,” he says.
The importance of dismantling the barriers to getting people tested and on sustained treatment is underscored by the emergence in the last decade of scientific evidence that shows when those living with HIV have an undetectable viral load, they are untransmittable to sexual partners — the concept of U=U. But the stigma preventing at-risk individuals from getting tested is only part of the problem, Dr. Landovitz says. He points to factors such as racism, sexism, homophobia and transphobia, along with larger failures of the health care and mental health systems. Black and Latino populations, in particular, continue to experience the highest burden of the disease. “On every level, we are failing people of color,” says Gail Wyatt, PhD ’73, of the efforts directed against HIV/AIDS.
As a member of the UCLA faculty in 1980, Dr. Wyatt — now Distinguished Professor of Psychiatry and Biobehavioral Sciences at the Jane and Terry Semel Institute for Neuroscience and Human Behavior at UCLA and director of the UCLA Center for Culture, Trauma and Mental Health Disparities — was the first person of color to receive a prestigious National Institute of Mental Health Research Science Career Development Award. Her focus was sex research, and with the initial AIDS cases, she began to study sexual risk-taking, including the impact of trauma and other mental health issues. In the four decades since, she has developed culturally congruent interventions for women and people of color — which she believes are in short supply in the HIV/AIDS field.
Dr. Wyatt laments that the current “one size fits all” approach to HIV prevention and treatment was developed for a population of gay white men that was highly motivated to seek care and had strong community-support systems. “It’s a colonial model that doesn’t address the barriers and issues for women and people of color, which are not the same,” Dr. Wyatt says. “Most diseases trickle down to poor, underrepresented people who don’t have good health care, and that’s where this disease is now. But the methodology for those populations hasn’t changed, and it’s been extremely challenging to get the funding to address the cultural and epidemiologic issues relevant to them.”
Within the broader context of national health care, the issues surrounding HIV/AIDS point to much deeper problems that plague our system as a whole, Dr. Wyatt says. “No matter how elegant the advances in medications are today, until HIV/AIDS researchers focus on the disparities in maximizing general health care overall, and in HIV/AIDS specifically, there will continue to be people of color who are at risk but who are not being adequately treated.” Four decades of research and clinical care count for little, she says, “if disparities in health and health care utilization, and the failure to address the historical roots of structural racism that inhibit diversity in leadership and in approaches to HIV/AIDS prevention, are not addressed.”
Dr. Wyatt’s sentiment aligns with that of other researchers in the field at UCLA. “We have to focus first on the groups where the disease is most represented, understand their conditions and bring in expertise to competently address the issues they face,” says Steve Shoptaw, PhD ’90, professor of family medicine and psychiatry and biobehavioral sciences and director of the UCLA Center for HIV Identification, Prevention and Treatment Services (CHIPTS). Dr. Shoptaw has devoted much of his work over the last decade to research involving Black men who have sex with men, a group affected by HIV at threeto- four times their representation in the population.
An addiction-science researcher, Dr. Shoptaw was drawn to HIV/AIDS research in the early 1990s, based on the fact that methamphetamine use has been a primary driver of HIV infection in Los Angeles. His epiphany came at a community meeting in 1992, where the prevailing belief was that methamphetamine-using men who had sex with men belonged at the back of the line in the distribution of HIV drugs. “I realized my understanding of how these behaviors engage risk in people’s lives was unique, and that we needed more people with expertise in both addiction medicine and infectious diseases,” Dr. Shoptaw says.
CHIPTS, which includes a multidisciplinary team of experts, studies and develops intervention strategies focusing on substance use, mental health disorders and social determinants that impair people living with or at risk for HIV from meeting their goals. It includes faculty like Dr. Shoptaw, with expertise at the intersection of addiction medicine and infectious diseases. His push for better integration of the two fields recently led to the first federal study targeting addiction for Americans living with HIV, which Dr. Shoptaw is co-chairing. INTEGRA, funded by the HIV Prevention Trials Network, will try to establish if using mobile health units to deliver integrated health services for people with opioid-use disorder can improve HIV and substance-use treatment and prevention.
News reports coming out of New York City in the spring of 2020 took Dr. Gottlieb back to the beginning of the AIDS epidemic. “The images of COVID ICUs reminded me of the early days in the respiratory-care unit at UCLA, where all of the beds were occupied by young men on ventilators with pneumocystis pneumonia,” he says.
Despite obvious differences, Dr. Landovitz can’t help but notice the echoes of HIV/AIDS in how the COVID- 19 pandemic has unfolded in the U.S. “We’ve seen the science move so fast it’s dizzying, but also some of the stigma and inequities of care playing themselves out again,” he says. “It’s a sobering reminder that science can move things forward, but we’re not always so good at learning the lessons from previous experience.” Adds Dr. Currier: “Both of these viral pandemics hold a mirror up to some of the huge cracks in our society in the way we treat each other, and in the disparities in our health care system.”
In 1984, U.S. Secretary of Health, Education and Welfare Margaret Heckler and Dr. Robert Gallo, the National Cancer Institute researcher who played a key role in the discovery of HIV as the cause of AIDS, announced that an HIV vaccine would come within two years. While effective COVID vaccines were developed in less than a year, 37 years after the announcement of an imminent HIV vaccine, it remains elusive.
It is not for lack of trying, says Irvin S.Y. Chen, PhD, founding director of the UCLA AIDS Institute. “From a scientific point of view, the AIDS virus is very different from the coronavirus,” he says. “With SARS-CoV-2, someone with the virus eventually will clear the infection and then have natural immunity. That hasn’t been the case with HIV — in which, in all but a few extraordinary circumstances, people stay infected for life, without ever developing natural immunity to clear the infection. HIV also becomes part and parcel of your DNA, which is why latency is such an issue. That’s not the case with SARSCoV- 2. And both viruses have a capability of mutating, but because there’s very little immunity to HIV, the virus tends to mutate more rapidly, which means that within any patient, there can be thousands of variants.”
Dr. Currier points out that COVID-vaccine researchers benefited greatly from the scientific advances that have come out of decades of HIV research — most notably, the use of messenger RNA technology, or mRNA, to induce cells to make a protein that triggers an immune response. Likewise, she and her colleagues are hopeful that the heavy investment in COVID research will bear fruit for HIV/ AIDS researchers in their pursuit of an effective vaccine.
The search for a cure also looms large, particularly in light of the side effects of current long-term HIV treatments. UCLA researchers led by Jerome A. Zack, PhD, chair of the Department of Microbiology, Immunology & Molecular Genetics and co-chair of the UCLA AIDS Institute, have contributed key findings on the matter of HIV latency — the concept that even with antiretroviral treatment to the point of undetectability, the virus tends to hide in the body and will quickly rebound once the drugs are stopped.
A major current focus of the international ACTG network, led by Dr. Currier, is to achieve antiretroviral therapy-free remission through drugs capable of awakening and killing the latent virus. But before promising approaches can be tested in the clinical setting, studies need to be done in the laboratory. In fact, lab-based research led by scientists at UCLA that was reported in January in the journal Nature Communications has demonstrated significant advances on that front. The work amplified earlier developments into a treatment strategy called “kick and kill” to target HIV-infected cells and reduce, or even eliminate, the amount of virus in an infected individual.
The approach utilizes a synthetic compound, administered in combination with antiretroviral drugs, to coax infected cells out of hiding and then kill them. “Our findings show proofof- concept for a therapeutic strategy to potentially eliminate HIV from the body, a task that had been nearly insurmountable for many years,” says UCLA infectious-diseases specialist Jocelyn Kim, MD, the lead researcher. Such bench research lays the groundwork for future clinical studies.
Dr. Chen and others have actively pursued a second important approach, using gene therapy in an effort to permanently modify the immune system. The research builds off of insights from “the Berlin patient,” a wellknown case in which a previously HIV-positive man from Berlin, Germany, remained free of the virus without antiretroviral drugs following a bone-marrow transplant from a donor with a rare gene mutation that confers resistance to HIV infection.
“That was an amazing finding, and it set the stage for research to mimic that approach through gene therapy,” Dr. Chen says. In laboratory research that started in the early 2000s, Dr. Chen’s group and researchers at Caltech used a technology known as RNA interference to eliminate the production of CCR5, the protein expressed on the surface of T cells that allows HIV to gain entry. The approach is currently being tested in human clinical trials.
On the morning of his final appointment with Dr. Mitsuyasu, Tom Gillman arrives at the CARE Center wearing a checked shirt, dark slacks and a blue surgical mask. He comes bearing plates of cupcakes for the staff, along with a retinue of family and friends: Bill Akell, his husband and partner of 23 years; Launa Romoff, the sister of a life partner who died from AIDS; and Bobbe Korbin, one of Gillman’s three older sisters. It is an emotional visit, during which doctor and patient ref lect on their nearly four-decades-long relationship. “I dreaded this appointment,” Gillman says as he takes a seat on a table in one of the clinic’s examination rooms. “I was very sad and insecure, like a child being deprived of something familiar.
When I come here, I don’t feel like I am going to the doctor; I feel like I am coming home.” Today, Gillman’s health problems are less directly related to AIDS — though there are some that are connected to the treatments he has received over the years — and more closely associated with those that would be familiar to any man his age. Within the last decade, he was successfully treated for prostate cancer. He now has physical limitations stemming from six back surgeries. But after close to 40 years living with this disease, Gillman remains a success story within the long, twisting saga of HIV/AIDS.
It is a success worth celebrating with a warm, lingering hug with the doctor who has taken care of him over these past many years. “I’m alive,” Gillman says. “There still are health issues, to be sure, but my problems have to do with being old. Seventy-five is just a number, but it’s an old number.”
Dan Gordon is a freelance writer and frequent contributor to U Magazine. UCLA Health senior writer Jocelyn Apodaca Schlossberg contributed reporting to this article.