Over the years, HIV has evolved into a chronic condition necessitating life-long medication. Now, researchers are studying the efficacy and acceptability of long-acting HIV medications that may keep thevirus under control for a month or longer. Can long-acting therapies provide an alternative to daily dosing? And, what do people who stand to benefit from this way of dosing think about the possibility of not having to take daily oral medications?

“HIV has been part of my life for 33 or 34 years, and medication for almost 20,” said Efrén Solanas, a long-term survivor in the Bay Area. “I’ve been taking pills for so long, that routine is completely integrated into my life. Wherever I go, I take my pills. But not having to get prescriptions filled, worry about copays, or remember when I’ve taken my pills would definitely be an attractive option. It would be amazing to not have to worry about those things.”  

Long-acting medications may be especially helpful for people who struggle with the routine of a daily pill.    

“It’s not difficult to take daily medications, but it is inconvenient,” said Guillermo Velez, a San Franciscan who seroconverted in 1995 and started taking antiretrovirals in 1996. “Sometimes I just forget. By the fifth day of the week, sometimes I think, ‘Did I take my medication yesterday?’ Instead of dosing again, I just skip a day.”

Over more than 20 years of taking antiretrovirals, Velez has experienced horrendous side effects, complicated regimens and inconvenient dosing. “It’s always a trade-off,” he said. “These medications made us miserable, but they kept us alive. Over the years, meds have gotten better. To think that a new medication is effective, and also delivered once a month by injection—that would be such a convenience. You wouldn’t need to worry about keeping the medication stocked, or filling those medication trays.”

At the IAS 2019 conference in July, Miranda Murray presented encouraging results from a study that looked at the acceptability of a long-acting cabotegravir/rilpivirine injection among people living with HIV.  

A total of 611 people were randomly assigned to continue daily oral HIV medications or switch to once-monthly injections. The researchers were interested in the experiences of people who switched to the injections, and assessed things like injection pain, overall acceptability of the treatment and if they would recommend the injections to other people living with HIV.

Overall, participants gave high acceptability ratings to the long-acting injections. Over the course of the study, people who received the monthly injections had a 13.7-point improvement in acceptability scores (from baseline to week 48).

There were very few discontinuations throughout the course of the study, and only four people (out of 303) had injection site reactions that led to withdrawal.

Most participants (90%) reported that injection site reactions (e.g., swelling) were either “totally acceptable” or “very acceptable.” 86% of participants said that pain from injections were either “totally acceptable” or “very acceptable.”    

Compared to people in the study who took daily oral medications, people who received the once-monthly injections scored more positively things like willingness to continue with the treatment, flexibility of treatment, convenience and willingness to recommend treatment.

“This indicates that the long-acting treatment meets participants’ expectations and supports the therapeutic potential of monthly dosing,” said Murray.

In April 2019, ViiV Healthcare applied for marketing approval to the U.S. Food and Drug Administration (FDA), and the FDA has set a target approval date of December 29, 2019. If approved, this treatment regimen would be the first-ever long-acting HIV treatment for people living with HIV.   

Source:

Murray, M. and colleagues. Patient views on long acting HIV treatment: Cabotegravir + rilpivirine as maintenance therapy (ATLAS 48 week results). IAS, 2019, Abstract MOAB0103. 

There’s a new antiretroviral, from a new class of medication, currently being tested for both PrEP and HIV treatment. Named islatravir (formerly MK-8591), this Merck drug is showing promise as part of a novel drug delivery system and because of its long half-life, great potency and high barrier for resistance.

Two presentations at the IAS 2019 conference in July shared Phase 2 study data on islatravir. Randolph Matthews, MD, PhD shared research of islatravir delivered through an under-the-skin implant, to test drug delivery at concentrations needed for the prevention of HIV. Professor Jean-Michel Molina, from Paris Diderot University, shared results from a dose-ranging study testing three different doses of islatravir, in combination with doravirine, to suppress viral loads in treatment-naïve adults living with HIV. 

“It is clear that PrEP and HIV medication alternatives are evolving,” said Christopher Hall, MD, MS, AAHIVS, vice president of medical affairs at San Francisco AIDS Foundation. “More options are needed especially for PrEP, because a single agent will never meet the needs of all people. Personal choice certainly will take on greater significance as alternatives evolve.”

Islatravir in a PrEP implant

Based on a design similar to that used for the Nexplanon/Implanon birth control implant, the islatravir implant is a removable implant designed to be inserted under the skin in the upper arm for a year. In the study presented by Matthews, researchers tested the drug concentration levels delivered by the islatravir implant over 12 weeks in 16 individuals.

In a double-blind, placebo-controlled study, the researchers tested two doses of the islatravir implant: 54 mg and 62 mg. Throughout the study, the researchers collected drug concentration levels in plasma and PBMCs, and were primarily interested in how much time the drug concentration levels fell below a threshold of 0.5 pmol/106 (a threshold which is believed to provide an adequate level of drug for HIV prevention based on animal studies).

At both doses, drug concentrations remained above the 0.5 pmol/106 threshold for the 12 weeks of the study, although the lower limit of the estimated range for the 54 mg dose dipped below the threshold for a brief period. The 62 mg implant delivered drug concentration levels well above the threshold for the duration of the study.

In a later analysis, the researchers projected that the 62 mg implant would lead to concentrations above the threshold for at least 12 months, falling below the threshold at around 16 months.

“This supports the potential of the islatravir implant as a once-yearly PrEP option,” said Matthews.

Future research, he said, will continue to test other prototype implants and additional doses.

“Just as in birth control, implanted, long-acting pharmaceuticals are likely to earn a place in the biomedical HIV prevention armamentarium,” said Hall. “While more study is needed, clearly the future of PrEP is one of greater alternatives, with agents that bring fewer side effects, are less susceptible to resistance, are easier to administer, and improve the experience of people who take them. The future promises a broader array of options than we have seen since the advent of FDA-approved Truvada for PrEP in 2012, and it is bright.”

Islatravir for dual-therapy HIV treatment

There are a few unique characteristics of islatravir that may make it suitable as part of a two-drug regimen, said Molina. In preclinical studies, islatravir showed more than 10-fold greater potency compared to other approved antiretrovirals. The drug is also known to act against a number of resistant HIV variants, has a long half-life and has a high barrier to resistance.

“This [two-drug regimen] may maintain efficacy comparable to a three-drug regimen,” said Molina. 

To test this, a double-blind study involving 120 treatment naïve adults living with HIV randomized participants to receive islatravir 0.25 mg, 0.75 mg, 2.25 mg or doravirine plus 3TC (lamivudine)/TDF (tenofovir disoproxil fumarate). At 24 weeks, or once viral loads were suppressed to <50 copies/mL on the triple-therapy, 3TC was removed.

There were very high response rates to the dual therapy at every dose level of islatravir.

After 24 weeks on the dual therapy, close to 90% of people receiving either islatravir 0.25, 0.75 and 2.25 mg with doravirine had viral loads <50 copies/mL. (96% of people receiving the control treatment of doravirine, 3TC and TDF had viral loads suppressed to this level.)

There were very few adverse events during the study, with two out of 90 participants receiving islatravir discontinuing the study because of adverse events.

“These results are quite promising, and demonstrate that the dual combination of islatravir and doravirine has the potential to be a potent, two-drug regimen and supports its further exploration in Phase 3 trials,” said Molina.

More research on islatravir’s safety and efficacy is needed before the drug may be granted FDA approval and brought to market. Based on the results of these studies, Merck plans to continue Phase 3 research on islatravir for HIV treatment as part of a once-daily, oral two-drug regimen. Using islatravir for PrEP, Merck is pursuing a Phase 2 study, set to begin enrolling in September 2019, that will evaluate the safety and tolerability of once-monthly oral islatravir.  

Sources:

Matthews, R. and colleagues. First-in-human trial of MK-8591-eluting implants demonstrates concentrations suitable for HIV prophylaxis for at least one year. IAS 2019, Abstract TUAC0401LB.

Molina, J. and colleagues. MK-8591 at doses of 0.25 to 2.25 mg QD, in combination with doravirine establishes and maintains viral suppression through 48 weeks in treatment-naïve adults with HIV-1 infection. IAS 2019, Abstract WEAB0402LB.  

• EMILY LAND, MAEmily Land is the editor-in-chief of BETA blog and content marketing manager at San Francisco AIDS Foundation.

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Black transgender women have one of the highest rates of HIV of any population in the U.S., with one study estimating an HIV prevalence rate of 56%. Yet the extent to which Black trans women are able to access HIV testing, treatment and care has not been well characterized. HIV and epidemiology data oftentimes lump relatively small numbers of trans women in with a much larger community of men who have sex with men—obscuring the experiences Black trans women have getting diagnosed and linked to care.

Now, a recent study highlights the startling disparities Black trans women experience in HIV diagnosis and care. In a study with 422 Black trans women from six U.S. cities, nearly 60% of women living with HIV were undiagnosed, only 38% were getting regular HIV care and about a quarter (24.5%) were virally suppressed.

“In the general population, only about 18% of people living with HIV are estimated to be undiagnosed, compared to the 60% of Black transgender women in our study that were undiagnosed. That’s a huge disparity,” said lead author Leigh Bukowski, MPH.

Tiommi Luckett

“These numbers aren’t really a surprise,” said Tiommi Luckett, from Positive Women’s Network, who was not affiliated with the study.

“We’ve been aware that Black trans women are falling through the cracks in HIV testing and care for a long time. We can fix this—but we’ve got to take a hard look at how our systems of care are failing Black trans women. And we have to be aware of what it takes for Black trans women to go in and get tested—if they’re welcome in the space, if they see themselves reflected in the staff, if transportation is an issue, and if they feel safe accessing services,” said Luckett.

Black trans women from across the U.S. participated 

Black trans women recruited from Black Pride events in Atlanta, Detroit, Houston, Memphis, Philadelphia and Washington D.C. participated from 2014 to 2017 as part of the Promoting Our Worth, Equality, and Resilience (POWER) study.

Participants completed an anonymous self-administered health survey which asked about their HIV status, HIV care, assault, violence, substance use, social support, incarceration, housing status, hormone use, discrimination, sex work and depressive symptoms. Participants were then offered confidential HIV testing, or anonymous HIV testing if the participant did not want to know their HIV status.

The average age of women in the study was 30.7. Most (78%) had health insurance coverage, and 44% reported being able to access health care.

Violence, discrimination and other forms of oppression were commonly reported by participants. About 36% had been incarcerated in the previous two years, more than half (55%) reported experiencing gender discrimination in their lifetime, and 46% reported experiencing racial discrimination in their lifetime. In the past year, 42% had been homeless, 19% reported sex work, 44% reported physical assault and 46% reported violence from an intimate partner.

HIV rates among Black trans women 

A total of 190 participants were living with HIV (45% of participants).

The researchers categorized participants as “undiagnosed HIV-positive” if the person tested positive on their HIV test, but indicated that they were HIV-negative or that they did not know their status on the survey. A total of 112 people were categorized in this “undiagnosed HIV-positive” group.

“One of the main findings was that almost 60% of Black trans women were undiagnosed at the time of the survey,” said Bukowski. She cautioned that this finding relies on self-report data, which may be influenced by participants’ reticence to state that they have been diagnosed with HIV on the survey.

There are many things that may prevent Black trans women from being able to access HIV testing services, said Luckett, a Black trans women who has been living with HIV for six years. Lack of transportation, housing, insurance, mistrust of traditional medical settings and other competing life concerns may all play a role.

“If am worried about where I am going to lay my head each night, or if I’m worried about how I’m going to feed myself, the last thing I want to worry about on top of that is an HIV diagnosis. If all looks bleak and hopeless, the last thing I want to find out is that I’m positive,” said Luckett.

Fear of a partner’s reaction can also be a significant barrier.

“You have to look at how violence shows up in people’s lives,” said Luckett. “We [trans women] are no different than anyone else. We want to be loved and feel loved. But a lot of times we’re looking for love in the wrong places. When our partners’ masculinity is threatened, we can become victims of violence. If I go and get an HIV test, and it comes back positive, I could be putting my life in danger.”

To bring in Black trans women, Luckett said that health care providers can incentivize testing with a meal or gift card and must go to where Black trans women already are.

“Come to where we are, because we don’t feel safe going where you are,” she said.

High rates of HIV care after diagnosis 

Although the percentage of Black trans women who indicated HIV-positive status on the suvey was low, most of those who did were already accessing HIV care. Of the 78 people who knew of their HIV status, 96% were linked to care, 92% were receiving regular HIV care, 83% were receiving HIV medications and 58% were virally suppressed.

This was “a bright spot” in the research, said Bukowski. Although the rate of undiagnosed HIV was high, most people who were diagnosed were receiving HIV treatment and care.

Women who reported being incarcerated, homeless, using three or more drugs, sex work and physical assault were less likely to be virally suppressed. It was a surprise to the researchers, said Bukowski, that hormone use was also negatively associated with viral suppression.

“When you consider the syndemic nature of heath disparities in this population, and all of the things that Black trans women are experiencing, perhaps it comes down to an either-or decision,” she said. “You can either get hormones or HIV treatment. And they prioritize hormones. In many places, these services are not co-located. So you’re not getting your HIV care in the same place that you’re getting your gender-affirming health care. When you’re faced with these obstacles, it might come down to, ‘What’s most important to me?’”

Luckett pointed to the importance of providing gender-affirming health care such as hormone therapy in the same place as HIV care. “Many women prioritize hormone therapy as more important than antiretroviral therapy,” she said. “Services must be as comprehensive as possible. We don’t always have access to the services we need.”

—

Source:

Bukowski, L.A. and colleagues. Characterizing the HIV Care Continuum and Identifying Barriers and Facilitators to HIV Diagnosis and Viral Suppression among Black Transgender Women in the United States. JAIDS, December 2018.

Testing for HIV is fast, confidential and freely available in many areas across the U.S. Yet an estimated 15% of people living with HIV—about 162,500 people—are living with HIV but have not received an HIV diagnosis. The CDC estimates that more than half of American adults have never been tested for HIV. What keeps people from finding out they are living with HIV, and what can we do to improve HIV testing rates everywhere?

Research by Ananda Ganguly and Joshua Tasoff from Claremont McKenna College sheds light on one reason why people living with HIV may not get tested: some people may not want to know if they’re living with HIV, and may go out of their way to avoid getting tested. Their research points to the importance of reducing fear and anxiety around HIV as a way to improve HIV testing rates. 

Although there are many reasons why people may not want or may not be able to get tested for HIV, Ganguly and Tasoff’s research explores “the ostrich effect,” a behavior where people knowingly avoid potentially negative information named for the false tale that ostriches bury their heads in the ground to avoid danger. People may resist receiving unpleasant information about their health—even when knowing the health information would be useful. Ganguly and Tasoff found that college student volunteers were willing to pay money not to receive results from an HSV (herpes) infection test.

“It’s like an ignorance-is-bliss result,” said Tasoff in a Hidden Brain podcast about the study.

In the study, student participants sat through an informational webinar about HSV-1 (which is typically associated with cold sores) and HSV-2 (which is typically associated with genital herpes), that included clinical pictures of herpes sores and rates of infection among college students.

The participants had their blood drawn, and were told that they could have their blood tested for free for both kinds of herpes. Study participants were assured confidentiality, and procedures were put in place so that even clinical staff for the study would not know the test results associated with individual participants.

To test for “information avoidance,” the researchers told study participants that they could pay $10 to not have their blood tested. A share of participants (5.2%) chose to pay to avoid an HSV-1 test. Moreover, a greater share of participants (15.6%) paid to avoid receiving an HSV-2 test. HSV-2 was judged to be “worse” or more stigmatizing than HSV-1 by participants.

“The avoidance is particularly conspicuous when we consider that the fee for an HSV test at the university’s student health center is $40,” the researchers said. “[Participants] are offered a test of potential high usefulness that would otherwise cost them $40… and yet still refuse to accept the test.”

Among people who chose not to have their blood tested, most (64.7%) said that they declined testing because the result might cause stress or anxiety.

There are certainly many reasons why some people living with HIV may not be aware of their infection. In some areas, easy and convenient HIV testing services may not be readily available. In surveys, people say that annoyance at having to wait for test results and the belief that they’re not at risk for HIV keep them from accessing regular testing. Fear and misconceptions also play a role.

“I have delayed getting tested out of fear,” said David, a San Francisco Bay Area resident. “The fear of getting a positive result still creeps into my head every time I test. Even with PrEP, and safer sex practices.”

Jimmy Gale, manager of HIV-positive services at San Francisco AIDS Foundation recalls the anxiety of testing for HIV, in addition to the fear of being judged by medical providers. “It’s even more terrifying if you don’t feel comfortable talking to your doctor about your risk factors or sexual behavior,” he said. “While many healthcare agencies have gone out of their way to be more open and inclusive to LGBTQ patients, some providers still feel uncomfortable if a patient shares intimate details of their sex lives.”

Brittany Maksimovic, manager of testing services at San Francisco AIDS Foundation recommends that people establish a regular HIV testing routine with a provider or clinic they trust as a way to reduce fear and anxiety about HIV testing.

The mobile testing unit of San Francisco AIDS Foundation provides confidential and free HIV testing services.

“Testing doesn’t have to be scary, and any good sexual health screening program will endeavor to make you feel heard and supported,” said Maksimovic. “If you experience anxiety around HIV testing, you aren’t alone—many of our clients report feeling similarly. Because we know it can be nerve-wracking (having been there ourselves!) my team goes out of our way to make sure that your sexual health screening feels comfortable and safe. And, if you do test positive for HIV, we will connect you to care so that you can live healthy and well. Knowledge is power, especially when it comes to your sexual health.”

“It’s important to test often. It will reduce your own anxiety and the more frequently you test, the easier it is to notify partners if you test positive for an STI. There are services available to help with partner notification, many of them can be done anonymously,” said Gale.

The number of HIV infections happening in San Francisco continues to decline, with a record low number of HIV infections occurring in 2017 than ever before. The rate of decline, however, is slowing.  As new data from the 2017 HIV Epidemiology Annual Report reveals, homeless people, people of color, trans women and people who use injection drugs are particularly affected.

“San Francisco has made incredible progress over the last decade reducing the number of new HIV infections. More people know their HIV status than ever before, and a greater share of people living with HIV are virally suppressed,” said Joe Hollendoner, CEO of San Francisco AIDS Foundation. “But we have much more work to do as disparities continue especially among African Americans, Latinx individuals, and people experiencing homelessness. Our vision of achieving the goals of getting to zero is closer than ever but in order to end AIDS we must continue to innovate upon HIV prevention and care services to ensure that no community gets left behind.”

5% decline in new HIV infections

In 2017, a total of 221 people were diagnosed with HIV in San Francisco. This represents a 5% decrease in the number of new HIV infections since the previous year, when 233 people were diagnosed. In previous years the percent reduction in HIV diagnoses was closer to 14% to 16%.

Susan Scheer, PhD, MPH, from the San Francisco Department of Public Health, noted that there were six populations that showed no declines in new HIV infections in recent years: African Americans, Asians, women, people who use injection drugs, men who have sex with men with a history of injection drug use and people who are homeless.

“San Francisco is doing an amazing job, and we have seen such change in recent years, but there are really important populations that we’re not reaching,” said Tracy Packer, MPH, from the San Francisco Department of Public Health.

HIV infection rates—which show HIV infections relative to population size—reveal disparities among communities of color. African American men (116 infections per 100,000) and African American women (43 infections per 100,000) continue to be disproportionately affected by HIV. (The infection rates in 2017 for white men and white women were 39 per 100,000 and 10 per 100,000, comparatively.)

HIV rates among African American women have increased since 2014 (from 5 per 100,000 in 2014 to 43 per 100,000 in 2017). The rate among African American men has increased over the past year, from 98 per 100,000 in 2016 to 116 per 100,000 in 2017.

Since 2006, HIV infections have declined the most among people who are white and also men who have sex with men—mirroring data on PrEP uptake.

The city now estimates that between 16,000 and 20,000 men who have sex with men are using PrEP in San Francisco (up from an estimated 12,600 in 2016; 10,000 in 2015; and 4,400 in 2014). Among San Francisco City Clinic PrEP clients, African Americans had the lowest proportion of PrEP use (34%) compared to clients who were white (50%), Latino (48%) and Asian (49%).

Among PrEP clients at community-based organizations including San Francisco Community Health Center, LYRIC, San Francisco AIDS Foundation, Instituto de la Raza and Alliance Health Project, Latino men who have sex with men were the most likely to start PrEP after being screened (58%). Trans women (25%) and African American men who have sex with men (44%) were the least likely to choose to begin PrEP.

HIV testing, care and viral suppression

San Francisco continues to make gains in the number of people that quickly get diagnosed, linked to HIV care and virally suppressed (which is best for individual health and also HIV prevention).

An estimated 94% of people living with HIV are diagnosed and aware of their status, which Scheer described as “very high” compared to the national average of 86%.

Among people newly diagnosed in 2016, 83% were linked to care within one month of their diagnosis, 71% were retained in care for three to nine months after diagnosis and 85% were virally suppressed within one year.

Among all people living with HIV known to reside in San Francisco, a number of populations had rates of viral suppression lower than the 74% average: women, trans women, African Americans, Latinos, people under age 50, people who use injection drugs, men who have sex with men who use injection drugs, and people who are homeless. The rate of viral suppression among people who are homeless was particularly low, at 32%.

“People experiencing homelessness have the lowest viral suppression rates of any population – less than half the average rate of San Franciscans living with HIV,” said Hollendoner. “Until there is more permanent supportive housing in San Francisco, we will continue to see this disparity. Housing is an effective strategy in ending the HIV epidemic as it has not only proven to improve viral suppression rates, it also prevents new infections from occurring. Bottom line: housing is health care.”

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Read the full 2017 HIV Epidemiology Annual Report from San Francisco Department of Public Health and find out about the innovative ways that San Francisco AIDS Foundation addresses health disparities and brings health services to communities of color.

Integrase inhibitors—potent antiretrovirals that quickly and powerfully suppress HIV—have allowed HIV researchers and clinicians to explore dosing regimens that involve fewer than three or four drugs. Proponents of dual therapy say that effective regimens involving fewer drugs will lower costs, decrease pill burden and reduce the potential for drug-drug interactions and side effects. But is it that simple?

Monica Gandhi, MD, MPH

“Two-drug regimens are exciting,” said Monica Gandhi, MD, MPH, medical director of the Ward 86 HIV clinic at San Francisco General Hospital and associate division chief of the Division of HIV, Infectious Diseases, and Global Medicine at UCSF. “But there are many clinicians who have been treating HIV for a long time that are a little bit alarmed over the two-drug fanfare. We’re not quite ready to jump on board with two-drug regimens for everybody.”

“On principal, fewer drugs is better,” said Keith Henry, MD, from Hennepin County Medical Center. “I like the philosophy of using fewer drugs, but I’m still not convinced that it’s going to be hugely beneficial. There may be only nuanced or subtle clinical advantages of a two- versus three-drug strategy evident over time—that we haven’t fully studied—especially if the drug you’re jettisoning is relatively non-toxic. In the U.S., most people that are on standard three-drug regimens are increasingly on one of the simplest, safest regimens currently available.”

Currently, there is only one recommended two-drug regimen option for people living with HIV, but the future may well bring more. Here’s a summary of challenges with the current option, and an overview of two other combinations currently being tested.

Dolutegravir plus rilpivirine

Juluca tablet (Photo: ViiV Healthcare)

Dolutegravir (integrase inhibitor) plus rilpivirine (NNRTI) is the only two-drug regimen currently recommended by the U.S. Department of Health and Human Services (DHHS). These medications can be purchased separately (no generic versions are available in the U.S.), so some people on this regimen take two pills once per day. This combination is also formulated as a single-tablet under the brand name Juluca, which is one tablet taken once per day.

This two-drug combination is not recommended for people just beginning antiretroviral therapy—it’s only a switch option for people who have been virally suppressed for at least six months.

Gandhi said that at Ward 86, the HIV clinic at San Francisco General Hospital, very few people are taking Juluca or dolutegravir and rilpivirine. The combination has been studied only in patients without a history of virologic failure, which is not common among people treated for HIV at Ward 86.  Moreover, the risk of drug resistance, and need for food security, makes this regimen only a good choice for people who are highly adherent to their medications—and Ward 86 sees many patients who are unstably housed, struggling economically or otherwise experiencing life challenges that can stand in the way of perfect adherence.

“The concern about a two-drug regimen and starting patients on this regimen is that if you lose something like dolutegravir [to drug resistance], that would make it really difficult in the future in terms of treatment options,” said Gandhi. “I think Juluca is very exciting, but it may be more so for people who haven’t had any failure to previous regimens and who are highly adherent. It’s not for everybody,” she said.

Another issue is that Juluca—a new drug approved in November 2017—is expensive, and the ease of a complete one-tablet regimen may be offset by its high price tag. Henry from Hennepin County Medical Center said that at his hospital’s pharmacy, Juluca can cost more than $38,000 for one person’s year-long supply.  (The wholesale acquisition cost is nearly $31,000/year.)

“If we purchase the tablets separately, it’s hundreds of dollars per month cheaper than that. If you look at what’s happening in society in healthcare in general, we still have to be good stewards of resources,” he said. “If you have individual small pills that are well-tolerated, I am not convinced that you always have to go with the single-tablet.”

Dolutegravir plus lamivudine

Dolutegravir plus lamivudine (3TC) is a promising two-drug regimen that is currently being studied. (It is not yet approved or recommended for use by the U.S. DHHS.) A generic version of lamivudine is available in the U.S.

At the AIDS 2018 conference in July, Pedro Cahn, MD presented results from the GEMINI-1 and GEMINI-2 studies comparing dolutegravir/lamivudine to a standard three-drug regimen of dolutegravir/tenofovir disoproxil fumarate (TDF)/emtricitabine (FTC). The study enrolled treatment naïve people who had not yet started antiretrovirals, with no evidence of drug resistance.

The researchers compared the percent of people who achieved viral suppression after 48 weeks between the two treatment groups, in addition to differences in CD4 count gains, adverse events and other safety and tolerability data.

Overall, the studies demonstrated that the two-drug regimen was non-inferior to the three-drug regimen: 93% of participants in the two-drug regimen and 94% of participants in the three-drug regimen achieved virological suppression at 48 weeks.

There were fewer drug-related adverse events with the two-drug regimen, and the two-drug regimen was also associated with better kidney and bone outcomes.

“As you well know, today ART means lifelong treatment,” said Cahn. “So as much as we can do to reduce drug burden for our patients is very welcome in terms of less long-term drug toxicity.”

Henry said that it will be interesting to see, as more efficacy data becomes available, what the differences might be between dolutegravir paired with lamivudine versus rilpivirine. He also plans to keep an eye on cost, and says this will continue to be a concern for patients and providers.

“This is part of the confusion of our health care system right now—and we’ll continue to have more of these dilemmas as time goes on and as we have more two-drug options and more generic drugs available. What is the real benefit of a single-tablet integrase regimen versus two or three small pills that are generic and much cheaper? If the single-tablet is 5% or 10% better tolerated or effective, but 45% to 50% more expensive, would a cost analysis support the use of the branded drug? We haven’t gotten into this as much as we should, but the overall state of healthcare financing means that we need to be more cost-benefit conscious.”

Cabotegravir plus rilpivirine

Cabotegravir LA vial and syringe (Photo courtesy of David Margolis)

Perhaps the most exciting two-drug regimen currently being tested is the long-acting formulation of rilpivirine and cabotegravir (which is an experimental integrase inhibitor). The dosing regimen now being tested frees people from taking oral antiretrovirals every day. Instead, people receive a long-acting injection once every four weeks or once every eight weeks.

So far, results of the LATTE-2 study, which is testing this formulation, are very promising. The injected cabotegravir and rilpivirine medications kept viral loads suppressed in 94% of people receiving injections every eight weeks and in 87% of people receiving injections every four weeks, when measured at the 96-week time point. People receiving the injections report high levels of satisfaction and convenience with the regimen, and also express willingness and desire to continue with this drug regimen.

If the long-acting injectable comes to market, Gandhi said she believes it could benefit people who struggle to take medication every day—in addition to people who are highly adherent (a bimodal population).

“We have many patients at Ward 86 who simply cannot fit taking a medication every day into their lifestyle, but, who actually show up to the clinic fairly often. People who are homeless may not come in for their primary care visits, but they show up for acute care visits. They’re engaging with the clinic a lot, which gives us hope that this will be an opportunity for treatment.”