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INFORMATION FOR

HIV/AIDS Care at Yale

May 18, 2022
by Ashley P. Taylor

Yale doctors have been caring for patients with HIV and AIDS since the first U.S. cases of what was at the time an unknown and deadly illness were reported in 1981. Over the last four decades, medical advances have transformed HIV into a chronic disease, which, if treated, barely shortens life expectancy. The HIV medicines called antiretroviral therapy (ART) can beat back, or suppress, the virus to undetectable levels. When patients with HIV are fully suppressed, as having undetectable viral load in the blood, they are less likely to transmit the virus to others, even though they still have HIV. It also allows them to live a normal lifespan. Phrases like “treatment as prevention” and “U=U” (undetectable=untransmissible) express this phenomenon. But HIV is far from eradicated. Even with medications to treat the virus and to prevent people at high risk from getting it, there are still about 35,000 new U.S. cases of HIV every year. “We can say, ‘wow, U=U, we’ve got powerful medications, look how far we’ve come,’” said Merceditas Villanueva, MD, director of the HIV/AIDS Program and associate professor of medicine at Yale School of Medicine (YSM). “And yet look how far we haven't come,” she continued.

Ensuring that everyone living with or at high risk for HIV has access to the prevention and treatment services that they need is the major hurdle now. “It's one thing to have the technology, which is great, but it's another thing to implement it in the community,” Villanueva said. Doing this—determining how best to use medical advances to improve people’s health in the real world—is called implementation science.

Implementation science is the heart of the work YSM faculty are doing in the areas of treatment, research, education, and community outreach. Frederick Altice, MD, professor of medicine and of epidemiology; Jaimie Meyer, MD, associate professor of medicine and public health; and Sandra Ann Springer, MD, associate professor of medicine and associate clinical professor of nursing, are developing and testing systems to prevent and treat substance use disorders and HIV in people at highest risk for both. Onyema Ogbuagu, MBBCh, associate professor of medicine and director of the HIV clinical trials program, leads trials of new treatments and prevention approaches. Lydia Aoun-Barakat, MD, medical director of the Nathan Smith Clinic, director of the Yale Infectious Diseases Ambulatory Services Program, and program director of the HIV primary care training track within the Yale Internal Medicine Primary Care Residency Program, trains primary care physicians who choose to specialize in HIV care. Villanueva, as principal investigator for the New Haven Ryan White HIV Continuum, works with community organizations to support patients underserved by the medical system.

Treatment: Frederick (Rick) Altice, MD

Today treating HIV is not difficult, according to Altice, an infectious disease doctor. “The medications are simple and safe and people who receive it are doing well. Your patients who are stable can now be seen once a year, if even that,” he said. The challenge now is overcoming the barriers, including substance use, homelessness, and incarceration, which prevent many people from accessing those treatments. “As an implementation science researcher, I work at reducing or overcoming such barriers so that those at the margin of society will have parity in terms of access to treatment,” he said.

About 30 years ago, in 1993, Altice developed one of the first mobile healthcare systems in the U.S. This 40-foot Community Health Care Van (CHCV), a bus repurposed as a clinic, provides free HIV prevention and treatment services to people in areas of New Haven where the risk for HIV and other medical problems is high. The van has a waiting area, multiple exam rooms, and bilingual staff. It offers HIV treatment and prevention services as well as primary care, mental health care, and treatment for substance use disorders. It also serves as the hub for the New Haven Syringe Services Program, one of the largest harm reduction programs in the country.

“I’ve heard people say ‘oh, you can't go out into the street, you're in a bad neighborhood.’ In reality, people in these neighborhoods feel respect when they can receive treatment on their own turf,” Altice said.

The CHCV was the first mobile medical clinic to provide buprenorphine treatment, an effective treatment for opioid use disorder. According to a 2017 demographic analysis, people receiving buprenorphine, a treatment for opioid use disorder that reduces cravings, visited the CHCV most frequently. People who were born outside U.S., used injected drugs, and who had hypertension also used the van at high levels.

The fact that the CHCV treats people with opioid use disorder relates to HIV because the virus can spread through contaminated needles. Helping people to stop or reduce using injected drugs, therefore, indirectly helps prevent the spread of HIV. Treating one’s opioid use disorder also improves HIV treatment outcomes by stabilizing them so that they can access and effectively treat their HIV. Several clinical research studies by Altice and Springer has found that people with HIV who receive treatment for opioid use disorder are more likely to maintain viral suppression.

Mobile health care systems work so well that they have spread from pioneers like Yale to cities and towns nationwide. Today the U.S. has an estimated 2,000 mobile health care units.

The CHCV physically brings health care to people in their neighborhoods. In a similar way, the expansion of telemedicine services during the pandemic has allowed people to get virtual healthcare wherever they were. “COVID was really the great implementation disrupter,” Altice said. When in-person visits became dangerous, healthcare systems had to adopt telemedicine. Medical professionals, including Altice’s team, documented that telemedicine worked. “We could diagnose people and effectively evaluate and engage them without seeing them in person. We could electronically provide prescriptions, have medications delivered to their home, and engage patients by phone or text. And our patients showed up for their virtual appointments, sometimes by phone if they did not have a smartphone, because they didn't have to travel by bus or arrange childcare,” Altice said. “Telemedicine has given people the convenience to receive their care in a way that is compatible with their lives,” Altice said.

Treatment: Sandra Ann Springer, MD

Infectious disease and addiction medicine doctor Springer is focused on preventing and treating HIV and AIDS by preventing and treating substance use disorders, in particular opioid use disorder (OUD) with medication treatment like buprenorphine and extended-release naltrexone. In her research program, InSTRIDE, she investigates how best to help people get treatments—for HIV and substance use disorders alike—and stick to them.

At the end of March, Springer launched a new study comparing two methods for doing this work: giving patients access to HIV prevention and treatment and SUD services on mobile health units and connecting them with patient navigators who link study participants to care at brick-and-mortar clinics.

Study participants have a history of opioid and or stimulant use, have or are at risk for acquiring HIV, and have recent involvement with the criminal justice system. Participants are randomized to treatment through the mobile health unit or to a patient navigator.

All study participants regardless of randomization will receive at baseline rapid HIV, HBV, HCV and STI (gonorrhea, chlamydia, syphilis) testing as well as a rapid diagnosis of OUD. Springer will use a validated Rapid Opioid Dependency Screen (RODS) that she developed several years ago and administered in less than 5 minutes by non-clinicians to enable rapid medication treatment of OUD if needed. “People are more likely to disclose use of substances asked in a non-punitive, non-threatening or stigmatizing manner,” Springer said. Depending on the results of their HIV tests, patients may either begin or continue ART, if they have HIV, or start pre-exposure prophylaxis (PrEP), a daily pill (or now a monthly injection) that prevents people from contracting HIV even if they are exposed to it. Patients with opioid use disorder will be offered treatment through medications, such as buprenorphine.

Participants randomized to patient navigator services will be linked to clinicians who offer similar services as provided on the mobile health units through brick-and-mortar clinics. Unlike the mobile health units, that the study researchers manage, brick-and-mortar clinics vary in the services they offer. As Springer noted, “this is the real world.” Another real-world aspect of the study is that although clinicians can prescribe treatments to study participants, they cannot control how quickly or even whether patients fill those prescriptions and start treatment, Springer said.

The primary outcome of the study is how long it takes patients to begin antiretroviral treatment, if they have HIV, or PrEP, if they are do not have HIV. The study will evaluate the full HIV/PrEP, HCV and OUD care cascades, including not just initiation of treatment but retention on treatment as well. Another important secondary outcome assessed in this study is the frequency of non-fatal and fatal overdoses, the number one cause of death for people released from jail or prison, Springer said.

The intervention period will last six months, during which time the researchers and patient navigators will do their best to connect participants to healthcare and other services in the community that they can rely on when the intervention ends. Currently, the mobile health units are only available to people through participation in studies like this one. At the one-year mark, the researchers will follow up with participants to find out whether any effects of the intervention lasted once the support of the study was removed.

The study is taking place in Tolland, Windham, Middlesex, and New London counties in Connecticut, some of which are rural, and they are partnering with Alliance For Living in New London, Connecticut, as well as in two Texas locations through collaborations with Texas Christian University, in Fort Worth, and University of Texas Southwestern, in Dallas.

For Springer and the other researchers working on this study, the work is more than research, said Cyndi Frank, PhD, RN, who directs InSTRIDE. The team tries to help patients with whatever problems they have, like unstable housing or lack of access to transportation or anything else, by connecting people with community organizations that can help, Frank said. “We use [research] as an opportunity to try to make people's lives better. And I don't say that lightly. Because everybody on our team functions that way,” Frank said.

Research: Onyema Obguagu, MBBCh

HIV treatment has advanced to the point where people with HIV can take pills only once a day or long-acting injectables to suppress the virus. “That’s just been huge,” said Ogbuagu. But taking a pill every day can be difficult. It can be exhausting—a phenomenon called pill fatigue. People facing mental illness, substance use disorders, unstable housing, and other barriers to treatment may be unable to take a pill every day. When people miss doses of their medications, HIV can develop resistance to the drugs. Multi-drug resistant strains can develop, such that even if you go back on some pills, they no longer work. Multi-drug resistance is also common in people who were infected with HIV from birth, according to Ogbuagu. To avoid the challenges of a daily pill, “the next frontier with regards to the advancement of HIV therapeutics is long-acting therapies,” Ogbuagu said.

Ogbuagu is leading a phase 2/3 clinical trial of lenacapavir, a long-acting treatment for multi-drug resistant HIV manufactured by Gilead. Antiretroviral therapies are categorized into several classes according to how they work, and HIV has developed resistance to all classes of drugs on the market. Lenacapavir is a capsid inhibitor; it works by interacting with HIV’s protein coating, the capsid. It also first-in-class, meaning that it is the first ever capsid inhibitor used to treat HIV. Because lenacapavir is a new kind of weapon against HIV, the virus is unlikely to have developed the ability to resist it. Additionally, because it is long lasting, administered as an injection every six months, it avoids the adherence problems of daily pills.

To be eligible for the trial, participants had to have HIV that was resistant to two drugs in each of three drug classes and to be failing their current drug regimens, as defined by having 400 or more copies of the virus per milliliter of blood. Participants were randomly assigned to receive either lenacapavir or a placebo. For the first two weeks, participants took a pill form of lenacapavir (or placebo) in addition to their failing drug regimen. The goal of this two-week oral lead-in, as it’s called, was to make sure individuals did not have adverse reactions to the drug before giving them a long-acting version of it. The reason for administering the drug alongside the failing regimen was to observe the effects of lenacapavir on its own—that is, without any other working drugs, Ogbuagu said. After this two-week period, 88% of participants who were taking lenacapavir had a significant drop in HIV levels compared with 17% of those taking the placebo. After that, the study was unblinded and all patients, whether they had previously received the placebo or oral lenacapavir, began receiving a subcutaneous injection of long-acting lenacapavir every six months alongside their failing regimen and one or two additional antiretroviral drugs, according to Ogbuagu. The reason for using multiple drugs, not just lenacapavir, was to prevent HIV from becoming lenacapavir resistant. After one year, Ogbuagu reported in February 2022 at the Conference on Retroviruses and Opportunistic Infections, 83% of study participants had an undetectable viral load.

“We've accomplished two things with these results,” Ogbuagu said. “We showed that lenacapavir added to the failing regimen, two weeks in, can have an effect on the virus. And then in the next phase of the study, we showed that in combination with other antiretrovirals, it could achieve and maintain viral suppression in patients.”

Ogbuagu and colleagues are also testing the drug in people who are just beginning HIV treatment and as a type of long-lasting PrEP.

Training: Lydia Aoun-Barakat, MD

Barakat is an infectious disease specialist and medical director of the Nathan Smith Clinic, which cares for patients with HIV at Yale New Haven Hospital. She is also helping to train future HIV physicians as program director for the HIV training track within Yale Internal Medicine’s Primary Care Residency Program, which she founded.

In 2011, Barakat was awarded a grant from the federal Health Resources & Services Administration (HRSA) to integrate HIV training into graduate medical education. There is a shortage of doctors interested in treating patients with HIV (PWH), in part due to the success of treatment allowing PWH to live longer. In addition, the doctors who had treated the first patients with HIV back in the 1980s were retiring, and there was not a sufficient workforce of new doctors who wanted to follow this career path, Barakat said. Many doctors want to be either infectious disease specialists or primary care providers, but patients with HIV need someone who does both. Patients with HIV “have many comorbidities, psychosocial issues. Now we are dealing with aging and neurological problems. You need a specialized physician who can meaningfully care for them. You need a person who knows HIV but is also well versed in geriatrics and primary care. And not many are interested in this role,” she said. Barakat, on the other hand, is very interested. “I wake up every morning excited about doing this work,” she said. And so do the residents who choose the Yale HIV training track.

The first residents within the HIV training track entered the program in 2013, and the program has continued ever since. The internal medicine residency program accepts two residents to the HIV training track each year. Since residency lasts three years, there is a cohort of six residents within the HIV training track. In addition to completing the general internal medicine curriculum, residents in the HIV training track participate in lectures, on-line modules, and case-based group discussions in topics of HIV medicine. They follow a cohort of patients with or at risk of HIV in the ambulatory clinic, the Nathan Smith Clinic.

At the end of their residency, trainees within the HIV training track are eligible for the American Academy of HIV Medicine certification exam and the American Board of Internal Medicine certification exams. About half of the graduates go straight into work as primary care doctors specializing in patients with HIV. Many choose to pursue infectious disease fellowships to become ID specialists. Some have gone into academic careers in internal medicine and HIV.

People who complete the training track are a much-needed group of physicians, according to Barakat. “Not every primary care physician knows how to take care of HIV patients. You can look at it as an intersection between infectious disease and primary care. And those residents, they have both. They have the primary care, and they have the HIV specialty competency as part of their training,” she said.

Community Engagement: Merceditas Villanueva, MD

As director of the HIV/AIDS program at YSM, Villanueva looks at the big picture of HIV treatment. Part of that picture is working with community organizations to overcome the barriers outside the domain of clinical research that have a real impact on people’s ability to get medical care. For example, some patients may struggle to take their HIV medications every day because they have unstable housing and don’t have a safe place to store them. Part of treating those patients may be helping them overcome such barriers by, for example, giving them a fanny pack for their meds. But there are some barriers that doctors alone cannot overcome, and that’s where community organizations come into play, according to Villanueva.

“There's only so much we can do in the clinical realm,” Villanueva said. “We know about drug interactions, we are up-to-date on new medications, but if we can't get patients into stable housing, or into a drug treatment program when they need it, the patient may not benefit. That's where we need our community partners,” Villanueva said. She has been working to strengthen the partnerships between Yale and community organizations since she became director of the Yale HIV/AIDS Program in 2009.

Before 2009, Villanueva said, community organizations in New Haven applied for and received Ryan White (Part A) grants, which are federal funds to support treatment of low-income people with HIV/AIDS. Back then, out of deference to community organizations, Yale did not apply for Ryan White funds, since it had other funding sources, Villanueva adds. But in 2009, the Ryan White Part A office changed its policy: Instead of many small agencies applying for funds, each eligible metropolitan area (such as New Haven) needed a Lead Agency, who would receive the funds and distribute them to community partnering organizations. “Along with others, I advocated for and organized to have Yale School of Medicine serve as the Lead Agency for New Haven,” Villanueva said.

When she first arrived, among community organizations “there was a generalized distrust of Yale, at least in the HIV community,” Villanueva said. Community agencies perceived Yale as a rich giant that was now trying to take away their funding, she said. When she proposed that YSM serve as the lead agency for Ryan White funds, community organizations responded with anger and distrust. “No other organization could come to the table and take the lead. Why? Because leading requires a degree of organizational capacity,” she added. That’s a capacity Yale has.

Yale has the business organization to administer subcontracts. Yale also has relevant clinical and public health expertise, as well as academic capacity to organize and track data that can be used to improve the quality of care. “We monitor the way the community does HIV/AIDS care, and we have fantastic statistics to prove it. We've got a 92% viral load suppression rate in our community,” she said. That means that HIV is undetectable in 92% of people who are being treated for HIV through New Haven’s Ryan White funding. "Bottom line is, we're now 12 years into this Lead Agency arrangement, and it's gone really well,” Villanueva said. “I've had great working relationships with the community agencies. They have accepted the partnership with Yale. In many respects, they've come to have a much better opinion of Yale because we work in the trenches together and we support one another particularly during challenging times such as the recent COVID pandemic. Our history of collaboration was leveraged in innovative ways to keep our patients engaged in care.”

The importance of seeing diseases in their public health contexts is something Villanueva wants to instill in clinicians of the future. “We can have all these wonderful ideas, but if we don’t bring them to the community, we’ve fallen short of our goal,” Villanueva said.

Submitted by Julie Parry on May 17, 2022