Is This the End of HIV
Is This the End of HIV?
Not yet, but Miller School researchers and clinicians are part of a decades-long effort that is closing in on a cure
By Josh Baxt
Illustrations by James Taylor
n the early 1980s, Savita Pahwa, M.D., was director of immunology at North Shore University Hospital in Long Island, New York, when an unnamed disease began killing children. She thinks about them often. “I remember all the beautiful children,” she said. “I had such close relationships with them.”
Dr. Pahwa wrote the first definitive paper about how a virus affected children’s immune systems. The disease was so new, the term human immunodeficiency virus, or HIV, didn’t yet exist. In the study, she called it human T-cell lymphotropic virus (HTLV-III).
At the University of Miami, physicians like Gwendolyn Scott, M.D., now professor emeritus of pediatrics, were also seeing how this new disease was affecting children.
“In the early years of the HIV epidemic, there was a lot of fear and stigma since we did not understand what caused the disease or how it was transmitted, and there were no specific treatments,” said Dr. Scott, an infectious disease specialist. “The mortality rate was incredibly high, and families were frequently alone in coping with it. Many infected infants suffered an early death.”
Around the same time, Margaret Fischl, M.D. ’76, professor of medicine and director of the AIDS Clinical Research Unit, and colleagues were treating adults with AIDS. Contrary to the “gay plague” epithet, they found the virus was affecting heterosexuals, particularly in the Haitian community. Initially, the U.S. Centers for Disease Control and Prevention rejected these findings, thinking the UM team was seeing a different disease, but eventually the agency came around.
HIV was finally identified in 1983, and that led to clinical progress. UM clinicians were among the first to provide antibody tests and culture the retrovirus to diagnose patients. Forty years later, physician-researchers at the Miller School are still on the cutting edge of HIV/AIDS research, working to understand the disease from many different angles, providing treatments and support for those living with the virus, and imagining a near future in which new infections drop by 90%.
“We’ve made amazing progress,” said Dr. Pahwa, “but the virus remains a master at evading the immune system. We know what it’s doing, we just haven’t been able to defeat it yet.”
A Tricky Virus
ART controls the virus but never fully destroys it. HIV knows how to play hide and seek with the immune system. Under treatment, the virus hibernates. If a patient stops taking their medications, it wakes up.
“HIV establishes long-lived reservoirs that persist indefinitely, even when people are on effective therapy,” Dr. Pahwa said. “That’s because the viral DNA integrates into the host genes in CD4 T cells. When they are in a resting state, there is no way to tell if it’s an infected cell or a normal one. The immune system just can’t see it.”
CD4 memory T cells are perhaps the most essential immune system components. They are also the main cells that HIV infects. CD4 T cells help B cells make antibodies, and CD8 (cytotoxic) T cells attack infected cells.
“They’re called memory T cells because they live a long time and rarely forget a pathogen,” said Mario Stevenson, Ph.D., professor of medicine and director of the HIV and Emerging Infectious Diseases Institute (HEIDI) at the University of Miami.
When the immune system knocks out a measles virus it first encountered during a tearful pediatric visit decades before, it’s CD4 T cells taking command. Active HIV destroys CD4 cells, eliminating that leadership.
Researchers have developed a strategy called “shock and kill” to root out the virus. The idea is simple: Shock HIV out of hibernation and destroy it. But that is easier said than done. HIV is built to mutate, and many of these mutations render the virus inert. This can make it difficult to determine which infected CD4 cells are dangerous.
But the greatest challenge may be in detecting where dormant HIV-positive T cells live. While it’s relatively easy to find infected immune cells in blood, there are other, more secretive hiding places. The majority of hidden HIV lives in immune cells, including myeloid cells, which patrol various tissues to fight off disease.
Even collecting myeloid cells for study is challenging. As a result, scientists don’t really know where the virus may be hiding. The liver? Lungs? Brain? Dr. Stevenson’s lab has developed an indirect way to find where viral particles originate: He simply asks them.
“We’ve found that the viral particles have these tiny molecular address tags,” Dr. Stevenson said. “If an individual discontinues therapy and the virus rebounds, we can collect it and look for its address label. We’ve developed assays that look at the composition of the virus that give us clues to what kinds of cell it originated in — T or myeloid — and where that cell was located.”
Understanding HIV’s secret life is a necessary early step toward shocking those hibernating cells awake and destroying them with ART or other therapies. But even that is tricky. Shocking T cells can generate a runaway immune response. Another strategy may offer a more nuanced approach.
“A large number of labs are looking at creative ways to eliminate these hidey-holes using gene therapy, immune modulators and antibodies,” Dr. Stevenson said. “They’re not trying to shock and kill but rather shock and lock. They’re not removing HIV, just making it inert.”
DESTROYING A VIRUS THAT HIDES✱
DESTROYING A VIRUS THAT HIDES✱
Countering Risk with Education
Longtime HIV fighter Sonjia Kenya, Ed.D., M.S., M.A., professor of medicine and public health sciences, is known for her unconventional approaches to reducing the incidence of HIV/AIDS in underserved neighborhoods. She explains how one of them — CHAMP (Community-based HIV Awareness & Testing for Minority Populations) — creates bonds with residents at risk.
By Joey Garcia
Illustration by James Taylor
Why is Miami-Dade — and especially Liberty City — the epicenter for new HIV infections in the United States?
Lack of access to culturally informed HIV education and to health care are the driving factors for excess HIV infections in Liberty City. There is no accessible, comprehensive HIV care in Liberty City, and to my knowledge, CHAMP is the only street-based team composed of culturally representative Black community health workers focused on reducing HIV in this community. While other health providers rotate in and out of Liberty City, most employ non-Black staff, which can function as a barrier to care since the team members don’t look like or speak like the population they’re attempting to serve.
Does knowing the “why” help combat HIV through better education, treatments or other initiatives?
Yes, knowing why people don’t practice protective sexual behaviors does help our team develop behavior-specific interventions. For example, CHAMP hosted a workshop titled “Are You the Side Chick?” in response to Liberty City residents telling us that numerous women were having sexual relations with the same man who was HIV positive. While the women knew they were in a non-monogamous relationship, they did not understand their HIV risk. As a result, the workshop we hosted prompted women to consider their sexual relationships within the context of HIV risk. Once they understood that non-monogamy was associated with increased HIV risk, they could make informed decisions about whether they wanted to be the “side chick.”
How do you reach out to the community?
We have numerous community engagement events several times per month and a robust social media presence in which community members can send us direct messages to obtain on-call services. At least once per month, we host a health awareness event addressing issues the community has brought to our attention. It’s not always about HIV — it’s about building healthier communities and trust with residents so they feel comfortable reaching out to us for assistance with HIV or any other health concern. Outreach is shared among the 12 team members, and specific community health workers conduct outreach at different times of day and night to ensure all residents have access. We have four full-time testers, and the last full year of HIV testing data showed CHAMP tested about 1,000 individuals annually, which breaks down to about 85 people per month. The rest of the team is focused on linking HIV-positive people to care and supporting them with medication adherence in order to achieve optimal HIV outcomes.
What are the demographic statistics?
Ninety-five percent of our participants are Black, and the remaining are majority Latin/Hispanic. We test people ages 13-82, and the median age of participants is 43 years old. With regard to gender, our sample is equally split between males and females.
Numbers are rising again. Is that because there was less testing during the pandemic? Or are there other factors?
The pandemic disrupted HIV care, and the World Health Organization has estimated at least 500,000 excess deaths from HIV would result from this disruption of services during the pandemic. Other contributing factors include reduced efforts from health care providers focused on HIV. With the onset of COVID-19, HIV funding decreased substantially, and HIV took a back seat in infectious disease control. Ironically, the same people who suffer from the worst HIV outcomes also suffer from the worst COVID-19 outcomes, and we did secure funding to address COVID-19 in our communities of focus.
HIV is a preventable disease. Why do people indulge in risky behaviors?
While HIV is preventable, many people of low socioeconomic status do not have easy access to condoms or PrEP, and they don’t know that these resources can be obtained free of charge at public health clinics. While much information is available, it is rarely conveyed in a culturally tailored manner to reach the populations that need it most. If condoms, PrEP and culturally representative community health workers were available at no cost on every corner of low-income neighborhoods, HIV disparities would not be so prevalent in these communities.
What new programs are you planning?
I plan to expand our street-based community health worker teams to other geographic locations where Black people suffer poor HIV outcomes. As current HIV therapies are underutilized by Black people and the cure for HIV will soon become a reality, it’s critically important to ensure trustworthy HIV-prevention efforts are in place to ensure Black people benefit equitably from these advances. My hope is these efforts help eliminate HIV disparities in Blacks and contribute to policy development enabling vulnerable Black patients to receive free support from culturally representative community health workers.
What do you think it will really take to end HIV?
Scientifically, we’re almost there, and I am confident a cure will be available within the next decade. However, to eliminate HIV among the most vulnerable populations, it is critically important for historically marginalized patients to know about the treatment and to trust HIV providers and the health care system so they feel confident in taking the treatment.
An HIV History
Eliminating HIV Through Prevention
any people are hoping for an HIV vaccine but developing one may take several more years. In the interim, the U.S. has set a goal to reduce new HIV infections by 90% by 2030.
ART will play a key role in meeting those numbers, and long-lasting injectable drugs are making it easier for people to comply with their medication regimens. When patients’ HIV becomes undetectable, it reduces the chance of transmission to near zero. In addition, PrEP helps keep at-risk people safe from infection. Community outreach programs, like those at UM, will play a significant role in expanding PrEP’s use.
“HIV was a death sentence, and then we had treatments, but people had to take hundreds of pills. Now we can treat people with one pill,” Dr. Pahwa said. “And if we can get enough people the right medications, we can reach that 90% goal and really reduce the HIV burden in our community.”
Dr. Stevenson is similarly optimistic. “We don’t have a cure yet,” he said, “but we’re knocking on the door.”
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