Is This the End of HIV?

n the beginning, we were involved in describing the epidemic — how it was transmitted, who was getting infected, the symptoms, the complications, the processes — and that put us immediately into the forefront of treatment,” Dr. Fischl said. “We began treating not only the complications –— pneumonias, serious brain infections, tumors — but we also began to realize that you could actually get at this virus. The first HIV drug ever tested was tested at the Miami site.”

Dr. Fischl and others at the medical school played a critical role in recognizing the value of AZT, the first FDA-approved drug to treat AIDS. Equally important, the drug tamped down virus transmission from mother to baby.

“One of our big triumphs was giving AZT to pregnant women and then to their babies for six weeks after delivery,” Dr. Scott said. “This decreased the number of perinatal transmission cases by two-thirds. It was a total miracle. They stopped the trial early because it was such a success. That was a real turning point for preventing HIV in children.”

Another breakthrough came in 1996, when highly active anti-retroviral therapy, or ART, transformed HIV from a deadly disease to a chronic one. People went from dying in a matter of months or a couple of years to living nearly normal lifespans.

There are now 35 FDA-approved anti-retroviral drugs. Children with HIV are surviving and even having children of their own. By bringing the viral load to undetectable levels, ART and other treatments have virtually eliminated transmission from pregnant women to their babies and between sexual partners.

With Miami the epicenter of the United States’ HIV/AIDS epidemic, accounting for one-third of new HIV diagnoses in Florida, Miller School faculty are actively working to help vulnerable, HIV-infected populations. One effort is the IDEA Exchange, Florida’s first legal syringe exchange program, which was co-founded by Hansel Tookes, M.D. ’14, M.P.H. ’09, associate professor of medicine (see page 22).

The Center for HIV and Research on Mental Health, or CHARM, directed by Professor of Psychology Steven Safren, Ph.D., focuses on helping people with HIV who may also have mental health and/or substance abuse issues. The goal is to help modify behaviors to improve their health and prevent transmission.

“We support investigators who conduct research related to HIV and mental health,” Dr. Safren said. “We are particularly interested in research that’s going to inform policy and practice and help the community, as well as getting HIV transmission to zero.”

Dr. Safren noted that pre-exposure prophylaxis (PrEP), a medication that helps prevent HIV transmission, can be incredibly effective. Unfortunately, PrEP is not being used consistently in many underserved communities.

“PrEP really helps with HIV prevention,” he said. “However, many populations don’t have access to it, and we want to address that disparity.”

Dr. Pahwa established Miami Center for AIDS Research, or CFAR, in 2007. One of 19 such centers around the country, the program spurred HIV research in South Florida. Dozens of scientists are channeling nearly $30 million in grants each year to study and control HIV. In addition, a new generation of researchers is benefiting from pilot grants and other funding. (CFAR is part of an interconnected network of UM research groups, including HEIDI, the Clinical and Translational Science Institute, and Sylvester Comprehensive Cancer Center.)

Drs. Tookes and Stevenson recently received a $3.1 million grant from the National Institute on Drug Abuse to determine how methamphetamine use affects the HIV virus in men who have sex with men. Called ARES, the study follows participants for six months, testing their viral loads, immune responses, psychiatric status and other markers to better understand how methamphetamine influences HIV progression. While the primary focus is community support, the ARES study will also give researchers in the Stevenson lab new opportunities to interrogate how methamphetamine use wakes up HIV-infected cells.

“One of our suspicions is that substances like meth might trigger the virus to be more alert — to be less in the slumber mode and more in the active mode,” Dr. Stevenson said. “It’s a double-edged sword. On the one side, active HIV is not good for the individual’s health. However, if the virus is more alert, it might be more visible to the immune system and antiretroviral agents. These are the mechanisms we want to understand.”

CHARM is a National Institutes for Mental Health-funded AIDS Research Center and also relies on philanthropy to support numerous research projects. As with CFAR, many studies are conducted by junior investigators. CHARM support helps jump-start their research and get external funding to expand their work.

One program, called CHANGE (Culturally focused HIV Advancements through the Next Generation for Equity), was launched in 2021 to train the next generation of HIV behavioral scientists. Led by Sannisha Dale, Ph.D., associate professor of psychology, and Daniel Feaster, Ph.D. ’00, and Viviana Horigian, M.D., M.H.A., both professors of public health sciences, the program trains predoctoral and postdoctoral fellows to pursue high-impact research and reduce mental health inequities in Black, Latino and LGBTQ communities.

“Science is failing minoritized populations in the U.S.,” Dr. Horigian said. “Adequate pipelines of training for the professional development of minoritized scientists are scarce, and research is not focusing effectively on the disparities affecting these populations. CHANGE is a result of our institutional commitment to combating racial injustice.”

Candice Sternberg, M.D., assistant professor medicine in the Division of Infectious Diseases, is working to improve HIV care and PrEP access in Miami’s Haitian community. Dr. Sternberg wants to partner with churches, television and radio stations and other groups to raise awareness about PrEP. As a Haitian American, she often uses her personal relationship with the community to help cement change.

“I have been able to do a lot of research there because I’m a member of the community and can speak to people in their native language,” Dr. Sternberg said. “I think people are more receptive to having someone from within the community talk to them about these issues and guide them to better care.”

ven 40 years after the virus was identified, researchers are still trying to understand how HIV operates. Maria Alcaide, M.D., a professor of medicine who studies infectious diseases and is director of clinical research at the Miller School, and Deborah Jones Weiss, Ph.D., professor of psychiatry and behavioral sciences and co-director of CHARM, are collaborating on several interdisciplinary studies to improve quality of life for people living with HIV.

Dr. Alcaide approaches these studies from the clinical side, while Dr. Weiss focuses on behavioral medicine. “My interest is not the clinical or lab part but the people part,” said Dr. Weiss. “Because HIV is complex, there are so many different behavioral issues around protecting yourself, taking care of yourself and not spreading the disease.”

Under their leadership, the Miller School is a major site for the MACS/WIHS Combined Cohort Study, a decades-long effort to investigate aging in people with HIV. “Most people living with HIV in the U.S. are over 50,” Dr. Alcaide said. “Although we have good ways to treat HIV and they can live long and healthy for many years, they are aging faster.”

The research team has received a seven-year, $14 million NIH grant to study these issues. Identifying the factors that precipitate accelerated aging could help many people live longer, including those who are not infected.

Drs. Alcaide and Weiss have also received a five-year, $15 million grant to study younger women infected with HIV, investigating the virus’s impact on reproductive, mental and oral health. Oral health is a particularly important component. In another study, called CROWN, the team is studying the confluence of oral and mental health and the impact on overall well-being.

“When people have inflammation, it’s not just in the mouth,” said Dr. Alcaide. “Inflammation can be systemic, and that has been associated with markers for other diseases, including heart disease. In addition, people with poor oral health may not eat well and have poor nutrition. It may also affect their sleep, which has an enormous impact on their quality of life.”

One of the major concerns is making sure people get the care they need. HIV patients must take their medications consistently for decades to remain healthy, and compliance can be an issue. However, Drs. Weiss and Alcaide are working to keep people in treatment.

“We’ve started using a strategy called motivational interviewing to help physicians reengage people in care,” Dr. Weiss said. “This has been quite effective, because it’s the people who stop taking their medication who are more likely to die from the virus.”

Separately, cardiologist Claudia Martinez, M.D., professor of medicine, is focusing on the dangerous triumvirate of HIV, inflammation and heart disease. She is leading a four-year, multi-center study, funded by a $2.8 million grant from the National Heart, Lung, and Blood Institute, to investigate elevated cardiovascular risk in HIV patients; some patients have had fatal heart attacks in their 20s or 30s. The study will examine factors on the surface of body cells — a type of lipids, called eicosanoids, that mediate inflammation — that react when HIV or certain other viruses invade them.

“The hope is to identify targets that will help decrease inflammation in its tracks, reducing cardiovascular disease, the No. 1 cause of death in this population today,” Dr. Martinez said. “No one has looked into this before, in part because the ability to measure the eicosanoid activity is a recent advance.”
Roger McIntosh, Ph.D., associate professor of psychology, is exploring how people living with HIV and other inflammatory conditions, such as cardiovascular disease, are affected by environmental factors.

“If people are immunocompromised but are also exposed to a lot of stress, that really breaks down their resilience,” Dr. McIntosh said. “My work is really looking at what type of psychosocial factors accelerate aging and other processes and what factors can instill resilience.”

He and his colleagues have been using functional magnetic resonance imaging and other techniques to look at how stress impacts the brain. Unfortunately, it’s difficult to re-create the kinds of stressors people experience in real life in the lab. To overcome that, Dr. McIntosh recently received a grant to bring the lab into communities, using an approach called ecological momentary assessments (EMA). The team is now collecting data in people’s day-to-day environments to better understand how stress may be impacting their biology.

“With psychological metrics, for example, if someone comes into the lab, we can ask them how stressed they’ve been over the past two weeks,” he said. “But there could have been a lot of high stress and a lot of low stress. We’re really just looking at averages. With EMA, we can look at moment-to-moment changes alongside biomarkers for inflammatory and cardiovascular risk.”

IV is incurable, but there are tantalizing hints that more effective treatments are on the way. A tiny group of four patients — one of whom was in a study Dr. Pahwa worked on — have successfully gone off ART. All four had HIV and leukemia and received stem cell transplants with cells lacking the CCR5 protein, which helps HIV enter cells. While this approach cannot be scaled for the larger HIV population, it has generated great interest as researchers pursue gene and other therapies targeting CCR5.

Ronald Desrosiers, M.D., Ph.D., professor of pathology, has a long history of working on HIV. He was the first to identify SIV, the primate version of the virus, and has had preclinical success with a potential HIV vaccine. The treatment is built around a rare species of broadly neutralizing antibodies. While patients generate antibodies against their own HIV strains, the mutating virus eventually escapes this response. However, some people make broadly neutralizing molecules that attack most HIV strains.

The Desrosiers lab has combined genes from these antibodies with a virus that delivers them to muscle tissue, where they essentially become antibody factories. Early-stage research in primates has shown this strategy can be quite effective.

“It has been seven years since we did the intramuscular injection in one of our models,” Dr. Desrosiers said. “Approximately 2% of all circulating antibodies today are coming from the gene we put into that muscle seven years ago. These potent, broadly neutralizing antibodies could prevent infection in high-risk individuals or treat those who are already infected.”

While this one-shot-and-you’re-done approach has shown genuine promise, there’s still a complication: The antibodies in the therapy are so rare and exotic that the body often treats them as intruders. As a result, these therapeutic antibodies are neutralized by the body’s own antibodies, negating their impact.

“Most of the work in my lab over the past few years has been focused on finding simple, readily applicable ways to create antigen-specific tolerance,” Dr. Desrosiers said. “We need to teach the body that these antibodies are not foreign.”