Keith Loria is a contributing writer to Medical Economics.

Keith Loria

home

authors

keith-loria

When it comes to HIV care—as opposed to HIV infection or HIV risk—the biggest challenges for trans people are access and discrimination, which are entwined.

, M.F.A., Ph.D., assistant professor of teaching, health, society, and behavior at the University of California, Irvine, spoke about HIV care issues in the trans community with 

What are the main challenges for trans people when it comes to HIV care?

American healthcare is obviously not designed to be easily accessible to people without health insurance, and trans people are more likely to be unemployed and/or financially precarious because of any combination of discrimination and mental health problems—most often brought on by discrimination and its subsequent trauma.

When trans people have the means to get healthcare, they face the challenge of finding care providers who are not just trans-friendly but are actually educated on trans health issues and know HIV care.

This is tough even when you are middle class, insured, and know how to navigate the systems. In major cities, this is easier but by no means easy. In Los Angeles, for instance, we have a more of such providers, and the county and state actually want to help, as opposed to states where the government is downright hostile. But unless you live in, say, Hollywood, you might have to travel three hours by bus to get to Hollywood if you can’t afford a car.

What can be done to meet some of these challenges?

I think it’s important to point out that a lot is already being done but many Americans don’t know or simply assume we wouldn’t ever be doing it.

Most importantly, the nearly 32-year-old Ryan White CARE Act has funded HIV/AIDS care for people who are under- or uninsured, so HIV care is not prohibitively expensive if you’re poor. In In fact, it’s free.

The Biden administration has stated that Ryan White funds can be used for gender affirming care and recommends that trans people get HIV treatment and hormone therapy in the same care setting. However, this information is not exactly put on billboards, so we need continued and expanded outreach to trans people about the services available of both HIV care and HIV prevention through PrEP (preexposure prophylaxis), which is covered by Ryan White funds.

That won’t matter, however, if the services aren’t available everywhere. Caregivers need to be trained on trans health issues, gender-affirming care, in addition to HIV care. I’d like to see governments provide incentives for caregivers to get that training, and I’d like to see these issues embedded in curriculums at medical, nursing and PA schools. Those schools shouldn’t be accredited without it being part of the curriculums.

What does the available data  on HIV and trans people show?

It is discouraging in most ways but also encouraging in a least one detail. In 2019-20, the CDC surveyed a little over 1,600 transgender women in seven cities in the United States, and 42% reported being HIV positive. That’s outrageously high, but the survey also asked about treatment and 90% of those who reported being HIV positive said they were on antiretroviral drugs.

We don’t know how many of them are virally suppressed, and we’d all like to see 100% of them on medications. But 90%means they’re accessing care. 

However, the survey didn’t include people not in those cities and obviously didn’t include people who weren’t comfortable being identified or self-identifying as transgender, so we need better information to know what’s really going on.

Articles

Ryan White funds can make HIV care affordable, even free, but there needs to be more outreach to the trans community, says University of California, Irvine, professor.

HIV Care and the Trans Community | A Brief Conversation With Theodore Gideonse, Ph.D.

Late last year, President Joe Biden released a new National HIV/AIDS strategy to provide the framework and direction for the administration’s policies, research, programs and planning through 2025. The plans have the lofty goal of ending the HIV epidemic in the United States by 2030.

New HIV infections have declined from their peak in the mid-1980s. People with HIV who receive care and treatment are living longer, healthier lives. But there were still 18,489 deaths among people diagnosed with HIV in 2020 in the U.S., and 650 000 AIDS-related deaths globally.

Biden administration’s strategy has the milestones of reducioing new HIV infections in the U.S. by 75%by 2025 and by 90% by 2030.

 and a former Harvard Medical School professor, noted the aim of helping communities take advantage of HIV services outside traditional healthcare settings through self-testing and mobile services is an important update to the government’s HIV/AIDS plans and something he has long advocated for. 

“The strategy also addresses hepatitis, substance abuse, mental health, and other STI syndemics often connected with HIV, taking a whole person approach to HIV care,” he said. “This pledge demonstrates a continued commitment to combating HIV both nationally and internationally and ending HIV transmission in the US even amongst other competing health crises such as Covid-19.”

Ending the HIV epidemic in the U.S. is a common if ambitious goal for the administration, some members of Congress, and the HIV community. Obstacles loom, though.

“EHE (ending the HIV epidemic) originated during the previous administration and resulted in increased federal funding for HIV testing, prevention, treatment, and the response to emerging HIV outbreaks directed at communities and states in which more than half of new HIV diagnoses occurred in 2016 and 2017,” said 

Clinical advances in HIV prevention and treatment have made ending the epidemic possible, said Jorstad, who used the “U = U” coinage, which stands for undetectable = untransmittable and is supposed to reinforce the goals of HIV 

So far, the Biden administration has reinstated the Office of National HIV Polic, which provides the leadership in development and implementation of the National HIV/AIDS Strategy (2022-2025). The administration’s FY 2023 budget request included $337 million to continue funding efforts to end the epidemic, as well as funding increases for existing federal programs across HHS.

The proposed funds include $165 million more for the Ryan White HIV/AIDS Program, $47 million more for HIV and hepatitis prevention activities at the Indian Health Service, and $115 million for CDC HIV prevention programs.

The FY 2023 budget request also proposed a national PrEP program to expand access to and uptake of PrEP.

“PrEP is a relatively recent addition to the HIV prevention toolbox but is only being used by approximately a quarter of people who would benefit,” Jorstad said. “Efforts to educate and train providers on PrEP as well as those to reduce stigma among providers can help. U=U is an important message that people living with HIV, providers, insurers, and communities need to hear.”

Beyond funding, Jorstad noted addressing individual, provider, and community-based stigma and engaging community stakeholders across sectors continue to be a challenge.

“Progress has been made to lessen gaps in HIV-related outcomes, but disparities exist,” she said. “Federal, state, local, and clinic-level data are being used to determine disparities and identify strategies to address them. Closing disparate gaps can require new or different approaches and will benefit from stakeholder buy-in at all levels, from community to executives.”

Preexposure prophylaxis and emphasizing the U=U (undetectable = untransmittable) message are central to the efforts to end the HIV epidemic, a goal that the Biden administration picked up from the Trump administration.

How President Biden Can Meet His Pledge to End HIV by 2030

Antiretroviral (ARV) medicines have significantly decreased mortality over the past 30 years, but treatment failure remains a concern, especially for heavily treatment-experienced  people living with multidrug resistant HIV.

ViiV Healthcare has publicized positive long-term results from its phase 3 BRIGHTE study of its drug, 

 (fostemsavir), that may seed hope that those treatment failures can be overcome. 

The results showed that people living with multidrug resistant HIV-1 who are "heavily treatment experienced" and treated for approximately five years with fostemsavir-based regimens, experienced durable virologic responses and continued clinically meaningful improvements in CD4+ cell count and CD4+/CD8+ ratio, according to 

, vice president head of global early development and research strategy at ViiV Healthcare.

Importantly, BRIGHTE study participants continued to show clinically meaningful improvements in CD4+ cell count and CD4+/CD8+ ratio, which is crucial for immune recovery, according to ViiV.

The study involved 371 people living with multidrug resistant HIV who are heavily treatment-experienced and have few treatment options left due to the significant complexities of resistance, safety, tolerability, contraindications and prior treatment failure.

“All trial participants were required to have a viral load ≥400 copies/mL and ≤2 classes of ARV (antiretroviral) medications remaining at baseline,” said Andrew Clark, global medical lead at ViiV Healthcare. “Trial participants were enrolled in either a randomized or non-randomized cohort.”

Within the randomized cohort, participants had one, but no more than two, fully active and available ARV agent(s) at screening, which could be combined as part of an efficacious background regimen. Randomized participants received either fostemsavir 600mg twice daily or placebo in addition to their current failing regimen for eight days of functional monotherapy. Beyond Day 8, randomized participants received open-label fostemsavir 600mg twice daily plus an optimized background therapy.

Within the nonrandomized cohort, participants had no fully active and licensed antiretroviral agent(s) available at screening, Clark explained. Nonrandomized participants were treated with open label fostemsavir 600mg twice daily plus optimized background therapy from Day 1 onward. The use of an investigational drug as a component of the optimized background therapy was permitted in the nonrandomized cohort.

Overall BRIGHTE study participants had very advanced HIV; 75% had a CD4 count <200 and 86% had a prior history of AIDS.

Lataillade noted that there are people living with multidrug resistant HIV who are often unable to benefit from newer therapies in existing classes due to complex resistance profiles. As a result, they can run out of treatment options. 

“In addition, most people living with MDR (multidrug resistant) HIV also have a poor immune system response to HIV despite ART,” he said. “What this data shows is that this specific patient population can take fostemsavir as part of their antiretroviral regimen and still experience a durable and favorable virologic response after a five-year period.”

Importantly, BRIGHTE study participants continued to show clinically meaningful improvements in CD4+ cell count and CD4+/CD8+ ratio, which is crucial for immune recovery.

ViiV Healthcare reports long-term positive results for its drug, Rukobia (fostemsavir).

Study Champions Rukobia For Some AIDS Patients

CAR-T therapies are a new and promising treatment for cancer. The global market for CAR-T therapies is projected to increase from $2.9 billion in 2020 to $11.8 billion by 2025, according to MarketsandMarkets.

But some major obstacles loom ahead, cost being one of them. A single CAR-T treatment can run into the hundreds of thousands of dollars. Although CAR-T therapy is a relative rarity now and therefore not a huge burden on payers, as the number of patients receiving it increases, so will the cost and payer scrutiny. The enthusiasm about the promise of CAR-T is also tempered somewhat by the risk of cytokine release syndrome, an adverse effect that can be life threatening.

CAR-T therapies involve genetically engineering a patient’s own T cells so they recognize and kill tumor cells.

Approved by the FDA in 2017, Kymriah (tisagenlecleucel) was the first CAR-T therapy to get the agency’s OK. Yescarta (axicabtagene ciloleucel) was next, approved a few months later as a treatment for large B-cell lymphoma in adults after at least two other kinds of treatment failed.

In 2021, the agency approved Abecma (idecabtagene vicleucel), the first CAR-T for multiple myeloma. And in February 2022, the FDA approved a second CAR-T therapy for multiple myeloma, Carvykti (ciltacabtagene autoleucel).

Sankalp Sethi, the cell and gene therapy practice lead at ZS Associates, has helped more than 25 oncology manufacturers commercialize cancer innovations and notes that this approval marks a strong gain in efficacy outcome.

“Nearly all patients (98%) in the study of Carvykti achieved a clinical response, and 78% achieved a stringent complete response,” he says. “Time is needed to determine how the product impacts overall survival, though many say that these results represent a new gold standard in CAR-T efficacy.”

Abhinav Deol, M.D., a hematologist-oncologist at Karmanos Cancer Institute in Detroit, says the recent spate of CART-T approvals is notable. In addition to Carvykti, the FDA approved Yescarta as a treatment for a broader group of patients with large B-cell lymphoma, Kymriah as a treatment for relapsed or refractory follicular lymphoma and Breyanzi (lisocabtagene maraleucel) as a treatment of patients with large B-cell lymphoma.

Deol also points to the ongoing trials evaluating allogeneic CAR-T cells, which would be available “off the shelf,” replacing the complicated process that involves using the patient’s own T cells. “Additionally,” he says, “there are ongoing studies looking at rapid manufacturing of autologous CAR-T cell product, thereby shortening the time it takes to have the product ready for infusion.”

Deol explains that CAR-T therapy provides another option for an increasing number of patients with cancers that have come back despite multiple rounds of other types of treatment.

“Long-term data in diffuse large B-cell lymphoma in the third-line setting shows that about 30% to 40% of patients can have sustained remission after CAR-T cell therapy,” Deol says. “Heavily treated (patients with multiple myeloma) can have disease control for over a year after one infusion of CAR-T cell therapy.”

For many patients, CAR-T represents their best potential option at a key moment of treatment eligibility. However, availability has been limited.

“These advancements mean these products can be more safely administered, more patients will be able to receive them and patients will be able to receive them earlier,” Sethi says.

“Remember, when CAR-Ts first came out, only a select number of centers of excellence were certified to administer. Given the complex nature of the products as well as the serious potential (adverse) effects, there was a need for providers to build more experience with the products before allowing for wider distribution.”

Progress has been made in overcoming some of the chief barriers to access to CAR-T, says Sethi, which include traveling distance for patients, management of adverse effects and financial viability of the administering centers.

“We are now reaching a stage where access is much more widespread — at this time, 70% of the U.S. population lives within 50 miles of a center that administers a CD19 CAR-T,” he says. “Geographic access to these products will no longer be a major barrier for most patients.”

Additionally, providers have become more comfortable handling the adverse events that come with CAR-T, he says. This means that for the right patients, outpatient administration is possible. Patients can stay with their families and caregivers while being monitored, improving their quality of life.

A recent study by ZS Associates also found that around 90% of CAR-T providers today are profitable overall with CAR-T administration.

“When first approved, CAR-Ts negatively impacted treatment centers’ finances, as reimbursement rates and mechanisms were still being sorted out,” Sethi says. “But we are now seeing that these centers have been able to become profitable through better management of (adverse) effects, applying markups and manufacturer discounts, and where applicable, receiving hospital-specific Medicare reimbursement adjustments. As a result, we expect more providers to be able to scale their capacity over time and offer CAR-Ts to more patients in the future.”

The supply chain and manufacturing challenges of CAR-T are center stage in discussion today.

Maria Whitman, global head of the pharmaceutical and biotech practice at ZS Associates, notes that Carvykti launched with a more limited number of certified centers (32) and limited manufacturing slots. This means that although patients and providers are eager for these products, the benefit is limited to a very small proportion of patients deemed eligible.

“Looking forward, it is also a source of budding innovation in support of patients,” she says. “Limited capacity and commercial availability are not only a challenge for meeting demand, but for scaling accessibility.”

For instance, Novartis recently unveiled T-Charge, a next-generation CAR-T platform that is expected to develop the cancer-finding T cells in the patient’s body instead of in a cell culture, reducing manufacturing time.

Gracell Biotechnologies Inc.’s proprietary FasTCAR platform is currently being evaluated in trials in China, and the company claims it has “next-day manufacturing” capabilities.

“Manufacturing turnaround times have long been a barrier to broader accessibility of CAR-T, and these developments are a strong sign that we are moving toward a future where patients are no longer waiting weeks to receive product,” Whitman says.

The high cost of CAR-T is another obstacle. CMS announced in 2019 that Medicare would cover CAR-T, but some provider groups have expressed discontent with what they say are low rates.

“One important thing to note is the cost for these advanced therapies can lead to sticker shock,” says Deol. “But the cumulative cost of other cancer therapies over a period of time is very high too, and CAR-T therapy is generally a one-time cost.”


Keith Loria is a writer in the Washington, D.C., area who covers healthcare.

More of these treatments have been approved, but supply chain issues and cost remain obstacles.

The Latest on CAR-T Therapy 

, a patient advocacy group whose funders include Pfizer, Gilead, Bristol Myers Squibb and several other pharmaceutical companies. Schmid has more than 20 years of experience advocating for HIV patients in Washington, including 16 years leading the AIDS Institute and building up its federal team. He is a cancer survivor and is living chronic hepatitis B.

Schmid has been a member of the President’s Advisory Council on HIV/AIDS under three administrations and served as its co-chair from 2018 to 2021.

What do you believe lawmakers should be doing to end HIV in the United States?


In addition to ensuring people have access to affordable and quality health care coverage, such as private insurance, Medicaid and Medicare, it is important that lawmakers fully fund the numerous domestic HIV programs that ensure there is adequate care and treatment for people living with HIV, such as the 

, and prevention programs, including HIV testing, at the CDC. With the proper funding, we can end HIV.

What are some recent efforts for getting to this point?

There is a concerted effort begun under the Trump administration to end HIV by 2030 with focused prevention, testing, care and treatment programs in the jurisdictions most impacted by HIV. This will take additional funding and Congress can ensure the goals of ending HIV can be met with the funding needed and proposed by President Biden. However, there is one element of the plan to end HIV that has not been adequately supported and that is a national PrEP (

) delivery system. PrEP are drugs that prevent HIV but not everyone who should be taking PrEP is utilizing it. This is particularly true for Black gay men and women and Latino gay men.

Congress has been very supportive of funding the Ending the HIV Epidemic initiative but not at the levels needed to meet the goals of ending HIV by 2030 and proposed by both Presidents Trump and Biden. Even with the dedicated funding for these efforts, COVID-19 put a monkey wrench in our plans to accelerate HIV elimination. But there are many competing interests and needs by so many communities. We hope as they finalize the spending bills for this year, they will maintain the proposed funding increases.

What would it take for the government to fund a national program?


President Biden has proposed a 10-year $9.8 billion new mandatory spending program that would fund a national PrEP program that covers medications, the office visits and ongoing associated lab work, along with community and provider outreach. Congressional passage of such a program — the legislative text hasn’t been developed yet — will take time to consider.

There are also congressional bills that would establish PrEP grant programs that public health entities can apply for. These programs are centered on the people eligible for PrEP who are uninsured and underinsured. Whatever happens, additional money will be needed and that is what we are pressing for right now.



How close are we to something like that happening?


Congress is considering the fiscal year spending bills now. Money is tight, and they have proposed increases for the Ending the HIV Epidemic initiative and other ongoing domestic HIV programs. We will continue to push for dedicated PrEP funding so that CDC and its grantees can undertake a national PrEP program, but if that does not happen this year, we must make sure CDC uses some of its existing dollars to support PrEP. Congress has also supported funding for community health centers to do more PrEP work and is considering increases this year to expand that work. We must also ensure that since PrEP is a USPSTF (U.S. Preventive Services Task Force)recommended service, private insurers must not charge beneficiaries for any costs for both the medications and the associated office visits and labs.


We desperately need a national program to promote and cover PrEP. We have established successful programs, such as the Ryan White Program, that provides care and treatment to low-income people who are living with HIV. It has been widely supported on a bipartisan basis. But we need a corresponding program to provide PrEP to low-income people who are at risk of HIV. There must be recognition that PrEP it is not just a pill or injection, but provider visits, ongoing lab tests and adherence services. We must also ensure that there is widespread community and provider outreach, particularly in those communities who are not taking advantage of PrEP. Special attention must be paid to the South, where the health care system and Medicaid expansion is lacking while at the same time HIV stigma is high.



Schmid, a long-time leader in the HIV advocacy world and executive director of the HIV+Hepatitis Policy Institute, says a national program to promote and cover the costs of preexposure prophylaxis (PrEP) is desperately needed.

A Conversation with Carl Schmid

Once-daily oral tablet regimens are the current standard of care for HIV treatment. The daily tablets were a leap forward from earlier regimens that required taking multiple pills a day.

But now many people living with HIV want treatments that are even less frequent than a daily pill, and drug developers are competing to meet the demand.

The interest and investment in longer-term HIV treatment got a major boost early last year when the FDA approved 

 (cabotegravir and rilpivirine), an injectable treatment that is administered monthly.

, a biotech company with offices in China and the United States, is one of the HIV drug developers vying for spot in the HIV treatment market. The company is developing two, once-weekly HIV treatment pills, provisionally named BRII0778 and BRII-732.

BRII-778 is an extended-release formulation of Edurant (rilpivirine hydrochloride), a nonnucleoside reverse transcriptase inhibitor (NNTRI).

“Edurant, an instant-release formulation of rilpivirine, has exhibited antiviral activity against a broad panel of HIV’s most common strains,” says David Margolis, M.D., Ph.D., vice president, head of infectious diseases at Brii Biosciences. “BRII-778, like all NNRTIs, binds to the NNRTI binding site which is a flexible allosteric pocket located at a site adjacent to the deoxyribonucleic acid polymerizing processing site, resulting in conformational changes and altered function of reverse transcriptase.”

Last year, Brii Bio completed the phase 1 SAD/MAD study of BRII-778 in the U.S. and selected one of the formulations for further development and evaluation in clinical trials. The data readout of phase 1 SAD/MAD trial for BRII-778 is expected to be presented at a scientific conference in the second half of 2022.

BRII-732 is a new chemical entity that is metabolized upon oral administration into EFdA (4'-Ethynyl-2-fluoro-2'-deoxyadenosine), which is also known as 

“EFdA functions not only as a potent chain-terminator like other NRTIs (nucleoside reverse transcription translocation inhibitors), but also as a potent HIV reverse transcriptase translocation inhibitor, with high binding affinity to the active site of RT, that inhibits HIV reverse transcriptase by blocking translocation of nascently synthesized strand for the next nucleotide incorporation,” Margolis says.

In April 2021, Brii Bio received clearance from the FDA for an investigational new drug (IND) application for BRII-732. The next month, a phase 1 trial that involved giving the drug to human patients got started.

However, in December 2021, the FDA placed a temporary hold on all islatravir-based clinical trials sponsored by Merck due to a decline in CD4 cell count in some subjects. BRII-732 is a prodrug of islatravir and was also placed on clinical hold out of abundance of caution and pending additional safety evaluations.

Based on the published data and information disclosed by Merck in December 2021, the safety finding of CD4 cell count decrease is both dose and time dependent. Brii Bio believes a safe dose of BRII-732 may be selected based on the Phase 1 study and will be efficacious for patients. The company plans to meet with the FDA to discuss plans to further investigate and develop BRII-732.

“Top-line data from the completed Phase 1 SAD/MAD study for BRII-732 showed that the therapeutic candidate is well tolerated without any CD4 cell count decrease observed,” notes Margolis.

Margolis says that HIV treatment has continued to evolve in important ways, to meet the priorities and preferences of people living with HIV.

Several safe and highly effective treatments have been developed in the past decade, the standard of care has always required daily dosing for life, to maintain viral suppression. However, daily oral dosing can complicate medication compliance and heightens the stressors of living with HIV, for some patients.

“Within just the past year, the first ever long-acting regimen, Cabenuva, was approved in the U.S. enabling injectable dosing every 4-8 weeks, freeing some patients for the first time ever from taking daily therapies,” says Margolis. “Research into additional long-acting approaches is being conducted in experimental clinical trials, including the potential for once-weekly oral options and self-administered injectable options, aiming to further reduce the medication burden and psychological burden of living with HIV.”

Brii Biosciences is one of the drug developers working on regimens that would free people living with HIV from daily pills.