Pharmaceutical company Gilead is ‘intentionally withholding’ a safer drug used for HIV treatments, a lawsuit claims.
The company holds the patent on Tenofovir Disoproxil Fumarate (TDF), an antiretroviral drug for people living with HIV. If routinely taken, this can regulate the viral load.
However, a lawsuit filed in US federal court on 17 November alleges that the company is withholding a new version of the drug with fewer side-effects to exploit patent laws.
The Food and Drug Administration (FDA) greenlit the new drug in November 2016.
According to the lawsuit, the company plans to sell a safer version of the drug called Tenofovir Alafenamide Fumarate (TAF). However, this will only happen when the patent on TDF expires in 2021.
Patent expiration means that cheaper, generic versions of the drug can be produced by other companies. If Gilead is timing the rollout for TAF to the patent expiration on TDF, they could continue to charge premium rates for the new drug.
The lawsuit claims that the company is ‘intentionally withholding [TAF] …from hundreds of thousands of patients in order to extend the profitability of the patent’. It says this has particularly impacted LGBTI individuals and ethnic minorities.
‘We are filing lawsuits on behalf of people with HIV who took one or more of Gilead’s TDF drugs—Truvada, Viread, Atripla, Complera, and Stribild—and then allegedly suffered kidney disease and/or bone density loss,’ the law firms announced on their website.
‘Gilead is accused of knowing that these drugs could cause serious side effects, but allegedly withheld a safer version of the medication (TAF drugs). Our law firms—Morgan & Morgan, Ben Crump Law, and Hilliard Martinez Gonzales—aim to hold Gilead accountable and recover money for people who claim they were harmed by these drugs.’
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.
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.
Health care experts have been informed of a US man contracting HIV despite being on PrEP. He’s thought to be the first man in California – and only the third in the US – to contract HIV while adhering to a daily PrEP regime.
PrEP is medication that mimimizes the chances of someone acquiring HIV, even if they do not use condoms.
News of the case was presented at the annual IDWeek conference in San Francisco, which concluded over the weekend. The conference is run by the Infectious Diseases Society of America.
The man was HIV negative when he began taking PrEP in San Francisco in late 2016. He continued to diagnose HIV negative when testing at three, six and ten months. Blood tests also demonstrated he continued to take his medication consistently.
HIV positive after being on PrEP for a year
After just over a year on PrEP, he received a HIV positive diagnosis in early 2018. He was immediately placed on HIV drugs and has maintained a suppressed viral load since that time.
Doctors were able to accurately diagnose the exact strain of HIV he picked up. It’s one identified with people who have taken HIV medication in the past but no longer take it. It was then revealed that the patient’s main male partner was HIV positive but no longer taking medication.
The partner was tested and found to have a high viral load of the resistant-strain. He has resumed taking medication.
Researchers say it was the fact the patient came into contact with a resistant strain that led to him acquiring the virus. They believe he stuck to his PrEP regime well. They could tell this from analyzing his hair, which he happened to grow long.
Dr Robert Grant, of the University of California San Francisco, said, ‘[The patient’s] long hair allowed us to test by centimeters, which allowed us to go back and read drug levels from six months ago.’
Previous cases of men becoming HIV positive while on PrEP
There have been five previous reports on men acquiring HIV while on Pre-Exposure Prophylaxis (PrEP). The first two occurred in Toronto and New York in 2016.
In 2017, there were three more cases. One involved a man in North Carolina, one in Australia, and a fifth a man in Amsterdam.
The first four cases are believed to be due to the person on PrEP having sex with someone with a high viral load of a rare, resistant strain of HIV.
The fifth case is not believed to be linked to a drug-resistant strain of HIV. The Amsterdam man had an ‘unusually high number’ of sexual partners – averaging 50-70 a month – and several other sexual infections. Researchers have speculated he may have repeatedly exposed himself to HIV, which took a hold in his body after a slight dip in Truvada levels.
‘Greater than 99% effective’
Health experts say despite these rare cases, PrEP remains highly effective. The medication is taken by more than 350,000 people worldwide.
Dr Grant said, ‘We know PrEP is greater than 99% effective. There are some cases where HIV will break through. We only have a handful of cases now, and next year, we’ll probably have a handful more. Fortunately, these cases are caught early, treated, and suppressed quickly. The person goes from taking one pill a day to one pill a day. The biggest difference is stigma.’
Matthew Hodson, Chief Executive of HIV information organization NAM, agrees.
‘We estimate that PrEP is more than 99% effective at preventing HIV. By comparison, a recent meta-analysis of the efficacy of condoms found that they prevented nine out of ten cases, this was a better result than previous analyses.
‘PrEP is still better than condoms at preventing HIV. PrEP failure makes news. Condom failure doesn’t.
He said that in the UK, 93% of people diagnosed with HIV have suppressed the virus to a point where it cannot be passed on ‘in any circumstance.’ This is regardless of whether it’s a drug-resistant strain or not.
‘It’s vital to acknowledge that PrEP, just like other safer sex strategies isn’t 100% effective. It is also vital not to let isolated cases obscure how effective it is. PrEP has played a significant role in bringing down new HIV infections in London, Sydney, New York, San Francisco and other cities around the world.’
San Francisco is making strides in reducing the number of new HIV infections that happen every year. But recent data released by the San Francisco Department of Public Health show that homelessness is a factor for HIV risk and in how people living with HIV receive treatment.
Homelessness and HIV are tightly linked. People who are homeless experience higher rates of HIV infection, have a more difficult time staying in HIV care and adhering to HIV medications, and experience worse health outcomes as a result of HIV infection. With nearly 7,500 homeless people in San Francisco, and 3,840 people who are unsheltered, the impact of HIV on our city’s homeless population is evident year after year.
“We’ve been saying it for years: housing is health care,” said Joe Hollendoner, CEO of San Francisco AIDS Foundation. “For many people living with HIV and experiencing homelessness, it can be difficult to access systems of care because of barriers like identification, insurance, or previous trauma. You might not be able to keep possession of medications because are forced to move or flee, or maybe you have to prioritize food over medication.”
“The HIV rate among homeless people is incredibly high,” said Julie Lifshay, MPH, PhD, of San Francisco AIDS Foundation. “And, homeless folks who are becoming infected with HIV are from more marginalized communities compared to people being diagnosed overall—they are more likely to be trans women, African American, people who use injection drugs, or men who have sex with men who use injection drugs. The good news is that people who are homeless are being linked to care at about the same rate as those who are housed and the percent who are virally suppressed within a year seems to be increasing.”
A large percentage of new HIV infections in San Francisco are among people who are homeless. A total of 31 people diagnosed with HIV (14%) were experiencing homelessness in 2017.
In 2017, 14% of all HIV diagnoses in San Francisco were among people experiencing homelessness.
Viral suppression not only improves the health of the person living with HIV, but prevents onward transmission. Only 32% of people who are homeless are virally suppressed, while 75% of people who are housed are virally suppressed.
Only 32% of people who are homeless and living with HIV are virally suppressed.
People who are homeless have higher viral loads on average than people with housing. And, the likelihood of being virally suppressed and viral load is related to the degree of housing stability.
In an analyses of people attending Ward 86 at Zuckerberg San Francisco General Hospital, percentage of people in each category of housing (renting/owning, in rehabilitation centers, in single resident occupancy hotels, couch surfing, in shelters or on the streets/outdoors) who were virally suppressed declined according to the level of housing stability each housing option offered.
Viral load declines as people are housed more securely.
The average viral loads of people in each category also increased with housing instability. People living on the street or outdoors had average viral loads over 85,000 compared to people in SROs (17,000) or those who were renting/owning (7,000).
It takes longer for people who are homeless to become virally suppressed. The average time to viral suppression for homeless people is 71 days, while it is 57 days for people who are housed.
People who are housed reach viral suppression more quickly.
Homelessness is a significant contributing factor leading to death in people with HIV who died in the last few years. Out of 50 people with HIV who died in the last few years, 30% were determined to have issues related to homelessness contribute to their death.
In one analysis, 30% of HIV death cases were determined to have issues related to homelessness contribute to cause of death.
“We know that homelessness is a main driver of new transmission,” said Susan Buchbinder, MD, director of Bridge HIV. “To get to zero new HIV infections and zero AIDS related deaths, we need to reach the homeless population.”
To reduce the impact of HIV on people in San Francisco experiencing homelessness, Tracy Packer, MPH, from the San Francisco Department of Public Health said that a new $2 million (yearly), 4-year grant from the CDC will allow the health department to scale up access to HIV, hepatitis C and STI testing and treatment plus PrEP for 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 Packer. “It’s not just about outreach. It’s about thinking through how we can change the system that we currently have to make it more accessible. Lower barriers to treatment, care, and to appointments.”
“One thing San Francisco AIDS Foundation has been able to do through our work at the 6th Street Harm Reduction Center is help people store their meds,” said Hollendoner. “Our outreach teams are also working to get people linked to care programs if they’re living with HIV but not receiving care. Our linkage and retention teams are also helping people living with HIV get into housing, and keep their housing. But these programs—while successful—are not enough. More housing is what we need to end the homelessness crisis, to build and maintain community health and wellness.”
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San Francisco AIDS Foundation has joined the Coalition on Homelessness to support Our City, Our Home, Proposition C, on the San Francisco ballot this November. If passed, Proposition C would fund permanent supportive housing, homelessness prevention, additional shelter beds and mental health and substance use services in San Francisco.
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.”
Britain’s High Court today ruled to overturn pharmaceutical company Gilead Science’s patent extension on Truvada. The HIV medication is also used for PrEP (Pre-Exposure Prophylaxis). When taken as advised, this stops HIV negative people acquiring HIV.
PrEP is not yet available on the NHS in England and Wales. The NHS is currently conducting a trial to test its cost efficiency. It is still in the process of recruiting around 10,000 high-risk participants for the ongoing trial.
Opponents of the NHS supplying Truvda say the medication is expensive. They point to the fact branded Truvada could cost the NHS up to £350 per month per person.
Supporters of PrEP say this is a price worth paying given its effectiveness. They argue the NHS has to pay more to provide a lifetime of HIV treatment to someone with HIV.
Currently, the NHS is only allowed to supply branded Truvada from Gilead.
Truvada was due to come off patent in July 2017, but Gilead extended its exclusivity until 2020 by a supplementary protection certificate (SPC). This prohibited smaller pharma companies from selling generic versions of the drug in the UK.
Generic versions could cost from around 80-90% cheaper, depending on the manufacturer. The NHS is often able to negotiate cheap deals because it buys in bulk.
The High Court today ruled against Gilead Sciences. The court’s decision follows a similar ruling in Ireland last year. There, those with HIV and or seeking Post-Exposure Prophylaxis treatment can use Truvada. Ireland does not yet offer Pre-Exposure Prophylaxis.
‘This represents a huge cost saving’
Many HIV and sexual health advocates welcomed today’s decision.
Deborah Gold, chief executive of NAT (National AIDS Trust) said: ‘We welcome this court decision, which overturns the patent extension for Truvada.
‘The decision will mean that unbranded versions of the drug can be legally prescribed. This represents a huge cost saving to buying a drug that would save public money, even at full price.
‘We continue to urge the NHS in England to commission PrEP by April 2019, as the current trial is not reaching everyone at risk. Indeed some have acquired HIV after being turned away from clinics whose trial places are full.
‘With the generic, unbranded version of the drug available at a fraction of the cost, the pressure increases on NHS England to begin routine commissioning, and make PrEP available to all who need it, urgently.’
‘I would urge NHS England to seize this moment’
Matthew Hodson, Chief Executive of HIV information organization NAM, also welcomed the judgement.
‘PrEP was already cost effective for people at high risk of HIV at Gilead’s price. This ruling should mean that much cheaper generic versions can be purchased by the NHS, ultimately saving even more money.
‘I would urge NHS England to seize this moment and swiftly rollout PrEP to all those who need it. This can be done in parallel to the existing trial.
‘PrEP has contributed to the significant declines that we have recently seen in HIV diagnoses among gay and bisexual men.’
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.”
As use of PrEP continues to grow, epidemiological evidence is starting to show a link between increased use and declines in new HIV infections. A study presented at the International AIDS Conference in Amsterdam shows an association between higher PrEP use and lower HIV incidence in the U.S. These figures highlight ongoing disparities in PrEP use, with some of the groups who need effective HIV prevention being the least likely to use it.
The Food and Drug Administration approved Truvada (tenofovir/emtricitabine) for HIV prevention in July 2012. For the past several years Gilead Sciences has been reporting PrEP use estimates from an ongoing survey of Truvada prescriptions at retail pharmacies.
Data from January 2012 through December 2017 show that the total number of people who have ever started PrEP exceeded 177,000. But PrEP still is only reaching a small proportion of those who might benefit. The Centers for Disease Control and Prevention (CDC) estimates that less than 10% of the nearly 1.5 million people at substantial risk for HIV infection are using it.
PrEP and new HIV diagnoses
Is increasing use of PrEP leading to a decline in new HIV infections? Trends in cities with high PrEP use suggest this may be the case.
In San Francisco, HIV incidence has declined steeply since the widespread adoption of PrEP in 2013, reaching its lowest-ever level in 2016. Dramatic declines in new infections among gay men have also been reported in London and Sydney. But stepped up HIV testing and the “treatment as prevention” effect of starting antiretroviral therapy immediately after diagnosis makes it hard to tease out the contribution of PrEP.
Patrick Sullivan from Emory University’s Rollins School of Public Health in Atlanta and colleagues from Gilead and the Centers of Disease Control and Prevention (CDC) looked at the correlation between PrEP use and new HIV diagnoses, using data from people age 13 and older in all 50 states and Washington, D.C., between 2012 and 2016.
A pharmacy survey examined a representative sample of anonymous prescription data from more than 80% of retail pharmacies in the United States, including independent pharmacies, chain stores, mail-order pharmacies and clinics. It did not include military or university health services or independent closed health systems like Kaiser Permanente.
Nationwide, the overall HIV diagnosis rate decreased significantly, from 15.7 per 100,000 persons in 2012 to 14.5 per 100,000 in 2016, an estimated annual decline of -1.6% per year. During the same period, PrEP use increased from 7.0 per 1,000 eligible individuals to 68.5 per 1,000, an estimated annual increase of +78.0%.
But there were some notable differences between states. The quintile or fifth of states with the highest PrEP use (11.0% of eligible individuals) saw a -4.7% decline in new HIV diagnoses. In contrast, new diagnoses actually increased by +0.9% in the quintile with the lowest PrEP use (3.5% of eligible individuals).
Estimated annual percent change in HIV diagnoses by U.S. states’ PrEP use, Slide: Patrick Sullivan
In an attempt to tease out the effect of PrEP versus treatment as prevention, the researchers also looked at viral load data from a subset of states, finding that PrEP use remained significantly associated with declines in new HIV diagnoses after controlling for levels of viral suppression.
“By documenting significant declines in average new cases of HIV in states where Truvada for PrEP has been most widely adopted, our analysis emphasizes the importance of improving access to HIV screening and a full range of prevention tools, including PrEP, in U.S. states,” Sullivan said in a Gilead press release about the study.
PrEP use among teens
Gilead researchers also did an analysis of PrEP use among young people, a group with a high unmet need for HIV prevention. In 2016, youth ages 13 to 24 accounted for 21% of new HIV diagnoses, according to the CDC. More than 80% of these were among young gay and bisexual men, with more than half among young black gay men.
The latest pharmacy survey numbers indicate that 15.4% of PrEP users are under age 25, with only 1.5% of them being 17 or younger.
People ages 12 to 24 accounted for 17.0% of all PrEP users in 2012. The proportion declined a bit during 2014-2016, as PrEP use skyrocketed among older gay and bi men, but then rose back to about the same level in 2017.
Breaking down the age distribution further, adolescents age 12 to 17 accounted for around 20% of PrEP prescriptions among people under 25 in 2012 and 2013. But, for unexplained reasons, both the proportion and the absolute number then started to fall, plummeting to 3.9% in 2016 and 2017.
In the early years of the survey, before gay men started promoting PrEP within their communities, a large proportion of PrEP users were women. In part, this reflected the use of PrEP to prevent HIV transmission within serodiscordant couples who were trying to conceive.
Today, the youngest PrEP users are still predominately girls and young women. Although women account for about 18% of PrEP users overall, they make up more than 80% of those age 17 and under. This disparity suggests that awareness of the need for HIV prevention, or willingness of providers to prescribe it, is greater for young women than for young men.
Adolescents ages 12 to 17 received Truvada for PrEP mostly from pediatricians, while family practice and internal medicine doctors provided most prescriptions for those 18 and older. A majority (59%) of PrEP users in the 17 and under age group received coverage through Medicaid, compared with 22% of those ages 18 to 24 and 13% of older adults. Nearly a third of those ages 18 to 24 and 38% of older adults obtained PrEP through commercial insurance.
Based on these findings, the researchers concluded, “there remains an important unmet need to improve awareness and engagement in HIV prevention for adolescents and young adults at risk for HIV.”
“I think that as we have seen in the news a growing presence of ICE in communities—despite San Francisco’s status as a sanctuary city—we are also seeing a growing trepidation and hesitation as people are seeking care,” said Liliana Schmitt, recruitment and retention coordinator for Clínica Esperanza at Mission Neighborhood Health Center.
Schmitt, who works with new clients at the clinic, said there are a variety of barriers that people from other countries seeking HIV care may face, but that clinic staff focus on making entry and retention in HIV care as easy as possible.
“We work with clients to figure out how to document things like identity, proof of income, residency, and insurance status—which can be difficult for many of our clients. Luckily, we have a lot of ways we can qualify that documentation. We don’t need official pay stubs, or an official lease or utility bill, for instance.”
HIV care staff at Clínica Esperanza and other HIV navigation and care centers in the Bay Area also work successfully with clients to figure out medication needs (for example, to find a similar medication to one the person had access to in another country), troubleshoot issues around traveling safely with HIV medications, and figure out how to pay for medications.
“These should not be limiting factors if you need HIV medications or PrEP,” said Schmitt. “It’s really important for people to know that many community sites and clinics in San Francisco—including ours—have payment programs and eligibility programs to help pay for HIV medications regardless of immigration or payment status.”
There are HIV care resources and protections for people of any immigration status in the Bay Area.
“It doesn’t matter what your immigration status is,” said Marco Partida, an HIV services navigator at San Francisco AIDS Foundation. “We are able to serve people regardless of what their immigration status is. We help people start or continue HIV care, get emergency supplies of medications, figure out how to pay for medications, and more.”
HIV navigation options in San Francisco
Navigation services help people living with HIV connect to any clinic or provider in the San Francisco Bay Area.
San Francisco AIDS Foundation staff provide services to all people living with HIV including people who are undocumented, people living with HIV and hepatitis C, transgender and gender non-conforming people, people who use drugs, and gay, bi and queer men. The team can help establish health care coverage and there are no insurance restrictions.
Call 415-602-9676 or 415-487-3000 and ask for the health navigator. Email assist4hiv@sfaf.org with questions.
St. James Infirmary provides navigation support for people who use drugs, current and former sex workers, and transgender and gender non-conforming people. Call 415-554-8497.
Shanti provides HIV navigation to all people living with HIV, including women, people who use drugs and people who are living with HIV and hepatitis C. Call 415-674-4760.
Glide provides HIV navigation to all people living with HIV, including people who use drugs, people living with HIV and hepatitis C, and transgender and gender non-conforming people. Call 415-674-6168.
HIV care options in San Francisco
The following clinics offer wrap-around care that includes medical care, benefits support and other social services.
Clínica Esperanza at Mission Neighborhood Health Center provides services for all people living with HIV, and specializes in care for Spanish-speaking and Latinx communities. Call Liliana Schmitt at 415-552-1013 x2234. http://www.mnhc.org/
Positive Health Program at Ward 86 provides HIV care for any person living with HIV. Call 415-206-2400.
San Francisco City Clinic provides care for people living with HIV including people who are uninsured or not currently in care. Call Andy Scheer at 415-487-5511.
A community march in Amsterdam, where the 22nd International AIDS Conference was held. Photo by: Matthijs Immink / IAS
AMSTERDAM — The fight to end HIV/AIDS was given a boost by a star-studded week of presentations, panel sessions and the occasional protest at this year’s International AIDS Conference in Amsterdam. However, tensions within the community remain, and with few new funding pledges announced, there are questions about how to translate strong rhetoric into action.
Some 16,000 stakeholders from more than 160 countries gathered in the Dutch capital last week for AIDS 2018, the conference’s 22nd edition and one of the biggest events in the global health calendar, featuring sessions on the latest HIV science, policy, and practice.
Held under the theme of “Breaking Barriers, Building Bridges,” the real story of this year’s conference was the growing realization that the HIV/AIDS epidemic is in crisis, with 1.8 million new infections in 2017. There are also alarming spikes in new HIV cases among key groups including adolescent girls in sub-Saharan Africa and drug users in eastern Europe and parts of Asia, according to recent figures from UNAIDS. At the same time, development assistance for HIV dropped $3 billion between 2012 and 2017, according to a study by the Institute for Health Metrics and Evaluation.
“The feel is definitely less congratulatory than past conferences and more sobering,” Rachel Baggaley, coordinator for HIV prevention and testing at WHO, told Devex, but added that it was good to see the community responding with force. The activist spirit which has defined the fight against AIDS in the past was never far away, she noted, with many sessions interrupted by campaigners.
“It is very positive to see the AIDS movement hasn’t gone away … I went feeling rather down and have come away challenged and inspired; there’s a lot of things we must do and a lot of people who continue to take this [AIDS agenda] forward,” she said.
One protest challenged the leadership of the U.N.’s dedicated AIDS agency, UNAIDS, with more than 20 female campaigners interrupting Executive Director Michel Sidibé — who has been criticized for his response to a sexual harassment scandal — during his address on stage at the opening plenary. Sidibé insists he has made changes and has resisted calls to step down, but his presence was a source of controversy.
The key now will be turning the strong rhetoric and passion seen throughout AIDS 2018 into action on the ground, according to youth HIV activist Mercy Ngulube.
“We are all going to build bridges this week … but where is your bridge going to lead us? Don’t let your bridge be a bridge to nowhere,” she said during the opening plenary.
A Devex team was on the ground throughout the week and rounds up the key takeaways.
1. Target key populations
Attendees agreed that, without drastic change, the world will see global HIV targets missed and a possible resurgence of the epidemic. But Peter Piot, founding executive director of UNAIDS and now director of the London School of Hygiene and Tropical Medicine, warned the targets themselves could leave key populations even further behind.
Speaking on Thursday, Piot reminded the audience that the 90-90-90 targets set by UNAIDS in 2014 will miss 27 percent of HIV patients. The framework calls for countries to get 90 percent of people living with HIV diagnosed; 90 percent of those diagnosed to be accessing treatment; and 90 percent of people on treatment to have suppressed viral loads by 2020.
“The 90-90-90 targets are actually 90-81-73,” he said, adding that “what the future of the epidemic is going to be determined by is the 10-10-10” — those not hit by the targets.
The 10-10-10 is likely to be made up of key populations including sex workers, men who have sex with men, LGBTI groups, people who inject drugs, and young people — all of whom are less likely to access HIV services due to social stigma, discrimination, criminalization, and other barriers, Piot said. These groups currently account for 47 percent of people with new infections, according to UNAIDS data.
Reaching these key populations was high on the agenda last week. Dudu Dlamini, a campaigner for sex workers’ health and rights who was awarded the Prudence Mabele prize for HIV activism during the conference, spoke to Devex about the need to decriminalize sex work in order to remove barriers to HIV services for sex workers.
Leading HIV scientists also put out a statement in the Journal of the International AIDS Society about laws that criminalize people with HIV for not disclosing their status and for exposing or transmitting the disease. Such laws, which exist in 68 countries, “have not always been guided by the best available scientific and medical evidence,” it said, and when used inappropriately can reinforce stigma and undermine efforts to fight the disease.
2. Prevention pay off
With new infections standing at 1.8 million last year, the recent UNAIDS report describes a “prevention crisis.” Traditionally, prevention has received only a tiny proportion of HIV funding, with the bulk going toward treatment. But there was a new buzz around the prevention agenda at this year’s event, in part driven by excitement around oral pre-exposure prophylaxis, or PrEP, which can prevent HIV infection among those at high risk. The antiretroviral medication has been successfully rolled out in North America, western Europe, and Australia, and has been shown to help reduce new infections among men who have sex with men.
WHO’s Baggaley said PrEP had “energized the prevention agenda.” However, questions remain about the feasibility of rolling it out in low-income countries, and about its efficacy for women.
“There is a prevention crisis and we need to find better ways of addressing it,” said Christine Stegling, executive director of the International HIV/AIDS Alliance. But while PrEP is a promising tool, a full approach to prevention needs to include a range of methods, combined with interventions that tackle human rights issues and gender inequality, she said.
3. A youth bulge
It was impossible to miss the strong youth presence at this year’s AIDS conference, which organizers said had a larger number of young people attending than ever before, and featured dozens of youth-focused events. This is linked to a growing recognition that adolescents face a disproportionately high risk of becoming infected with HIV, especially in Africa where the population is set to rapidly increase, and where new infection rates are on the rise among young people.
Ugandan youth advocate Brian Ahimbisibwe, a volunteer ambassador for the Elizabeth Glaser Pediatric AIDS Foundation, said: “Without the youth, the future of all these conferences, and more importantly [of] services and programs, [is] compromised.”
However, 28-year-old Tikhala Itaye, co-founder of women’s rights group Her Liberty in Malawi, said the youth voice had not been fully integrated and that young people were still being “talked at” during many of the sessions, as opposed to being listened to.
“There’s now acceptance that young people need to be at the center … they do have the demographic weight and power to influence issues around HIV,” she said, but “you still find the different youth events happening in different rooms … Why aren’t we all coming together as one to build the bridges and have a global voice?”
Signs at the 22nd International AIDS Conference in Amsterdam, The Netherlands. Photo by: Marcus Rose / IAS
4. The need for integration
A number of sessions talked about the need to integrate HIV programming, which has traditionally been siloed due to having its own funding streams, into broader health care. This was a key message of The Lancet Commission report on strengthening the HIV response published ahead of the conference, and was also the message delivered by WHO director-general Tedros Adhanom Ghebreyesus during the opening plenary.
“We have not truly helped a child if we treat her for HIV, but do not vaccinate her against measles. We have not truly helped a gay man if we give him PrEP but leave his depression untreated … Universal health coverage means ensuring all people have access to all the services they need, for all diseases and conditions,” he said.
Baggaley said integrating HIV into the broader health agenda posed both “an opportunity and also a challenge and risk for those populations most marginalized,” explaining that key populations currently served by externally funded nonstate health services could see their assistance diminished under UHC if the country in question did not believe UHC includes key populations or had punitive laws against gay men or sex workers, for example.
There was much discussion around the need to combine HIV and tuberculosis efforts, especially in the run up to the first U.N. high-level TB event in September. TB is the number one killer of people with HIV, who are up to 50 times more likely to develop it, according to WHO.
Speaking in between interruptions from the crowd, former U.S. President Clinton highlighted the need to address HIV and TB in tandem during the closing plenary and called on world leaders, notably India which has the highest TB burden, to attend the upcoming U.N. TB meeting.
“If you think … anyone ..that we can possibly bring the developing world to where we want it to be by abandoning the fight against HIV/AIDS and the collateral struggle against TB, you need to think again,” he said.
New findings from the Sustainable East Africa Research in Community Health program, presented during the conference, showed positive results from a community-based program which combined HIV testing and treatment with other diseases including TB, diabetes, and hypertension. The findings of a three-year randomized controlled trial in Kenya and Uganda showed that communities receiving testing and care for HIV alongside related conditions saw nearly 60 percent fewer new TB cases among HIV-infected people and that hypertension control improved by 26 percent.
5. Medical developments
Concerns about GlaxoSmithKline’s so-called “wonder drug” dolutegravir, which a study recently suggested might be linked to serious birth defects among children in Botswana, sparked debate amongst conference goers about whether potential mothers should be prescribed the drug.
WHO already advises that women of childbearing age wishing to take the antiretroviral have access to effective contraception, and will be re-evaluating its guidance as new evidence emerges, Baggaley told Devex. But there are concerns the agency could introduce blanket restrictions for women of childbearing age, which would force them to take other antiretroviral drugs that have worse side effects. The controversy could also lead to delays in the rollout of other forms of the drug, such as a pediatric version.
The conference also featured new data from the APPROACH study, which is evaluating the safety of several different HIV vaccines currently undergoing clinical trials in the U.S., East Africa, South Africa, and Thailand — but researchers admitted a vaccine will take years to develop.
6. The Trump effect
The shadow of U.S. President Donald Trump’s beefed-up “global gag rule,” otherwise known as the Mexico City Policy, loomed large over the conference, and a number of sessions discussed how it is negatively affecting HIV programs. Unlike previous iterations of the policy — which restricts U.S. funding to non-U.S. organizations that offer services related to abortion — Trump’s version is applied to almost all U.S. global health assistance, including PEPFAR.
Santos Simione from AMODEFA, an NGO that offers sexual health and HIV services in Mozambique, said his organization had lost U.S. funding due to the gag rule and was forced to close half of its youth clinics, which offered sexual and reproductive health services alongside HIV testing, counseling, and antiretroviral therapy.
“We could not provide condoms … testing … we just stopped everything,” Simione said.
Participants also spoke of a chilling effect, whereby organizations have stopped offering services that may not actually be prohibited under the rule, and raised concerns about PEPFAR’s staying power within a hostile Trump administration.
Meanwhile, there was heated debate about arrangements for the next conference, which the International AIDS Society has said will take place in San Francisco, California, in 2020. The decision has been met with fierce opposition and threats to boycott the event from AIDS campaigners who say many key population groups affected by HIV will have difficulties attending due to strict immigration policies. In 2009, former U.S. President Barack Obama lifted a restriction banning people with HIV from entering the country, but sex workers and people who use drugs still face legal challenges entering.
