Mary Rodgers, a principal scientist at Abbott whose team published their findings on Wednesday in the Journal of Acquired Immune Deficiency Syndromes, said there was no reason for the public to be excessively concerned about the newly discovered HIV subtype, which they believe to be extremely rare.
But the scientists said the discovery of the new strain — called HIV-1 Group M, subtype L — should serve as a reminder of how diverse and continually evolving HIV viruses are, and how necessary it is for medical and research communities to remain vigilant.
“We can never become complacent, we need to be proactive and we’re working to stay a step ahead of the virus,” Rodgers told the Chicago Tribune.
“Identifying new viruses such as this one is like searching for a needle in a haystack,” Rodgers added in a statement. “This scientific discovery can help us ensure we are stopping new pandemics in their tracks.”
The identification of a new HIV subtype “tells us that the HIV epidemic is still ongoing and still evolving,” immunology expert Jonah Sacha, who was not involved in the Abbott study, told Scientific American.
“The calling card of HIV is its diversity. That’s what’s defeated all of our attempts to create a vaccine,” said Sacha, a professor at the Vaccine and Gene Therapy Institute at Oregon Health & Science University. “People think it’s not a problem anymore, and we’ve got it under control. But, really, we don’t.”
The Trump administration on Wednesday sued Gilead Sciences, a pharmaceutical company that sells H.I.V.-prevention drugs that can cost patients up to $20,000 a year, accusing the company of earning billions from research funded by taxpayers without paying taxpayers back.
The government said the company infringed upon patents owned by the Department of Health and Human Services, and had refused attempts by the department to license its patents and collect royalties. The company sells two drugs, Truvada and Descovy, that can be taken once daily to prevent H.I.V. infection, a strategy called pre-exposure prophylaxis, or PrEP.
Wider access to PrEP is central to the government’s goal, announced in February, to reduce new H.I.V. infections by 75 percent over five years, and to “end the H.I.V. epidemic in America” by 2030. Critics have said the drug’s lofty price tag has limited its accessibility to high-risk people with low incomes, thwarting the government’s efforts.
Gilead is already facing a separate class action anti-trust suit filed by six AIDS activists including Peter Staley.
The National Institutes of Health announced on Oct. 23 it is launching a $100 million initiative over the next four years to fund research to develop gene-based cures for HIV and sickle cell disease.
The NIH announcement says the initiative will work in collaboration with the Bill and Melinda Gates Foundation, which will also invest $100 million toward gene research for an HIV and sickle cell disease cure.
“Dramatic advances in genetics over the last decade have made effective gene-based treatments a reality, including new treatments for blindness and certain types of leukemia,” an NIH statement says.
“The collaboration between the NIH and the Gates Foundation sets out a bold goal of advancing safe, effective and durable gene-based cures to clinical trials in the United States and relevant countries in sub-Saharan Africa within the next seven to ten years,” the statement says.
Dr. Anthony Fauci, Director of the National Institute of Allergies and Infectious Diseases, which is an arm of NIH, told the Blade the new initiative is aimed at taking gene research to a new level that has yet to be developed. According to Fauci, the goal is to develop a means of genetically altering disease fighting cells in the body to enable them to protect against HIV through a single injection.
He noted that the current line of research, which is nearing the stage of clinical trials on humans, involves withdrawing blood from the body, extracting disease fighting T-cells from the blood in a laboratory, genetically changing the cells to enable them to successfully kill HIV and prevent someone from being infected, and then to “reinfuse” the altered cells back into the person’s body.
This is a highly expensive process that requires hospitalization, Fauci said, making it difficult to put in place for the large number of people who need it, especially populations in developing countries in Africa.
“We’re talking about something that is highly aspirational with an extremely high reward,” he said. “That is to develop a delivery system that you can essentially with one injection give it to a person and have that delivery system bring the appropriate gene editing tools to whatever cells you want to bring them to,” he said.
Fauci said this system, if it can be technologically achieved, would provide a genetic cure for HIV that could become available on a massive scale in the U.S. and developing countries throughout the world.
“Whether or not we’re going to succeed, we don’t know,” he said. “But we’re going to try.”
He said the combined $200 million from NIH and the Gates Foundation would be made available to qualified independent researchers or researchers affiliated with universities or with private companies working on gene editing technology.
One such company, American Gene Technologies of Rockville, Md., has developed a gene editing process for a possible HIV cure that it believes is ready for human testing. In an announcement last month, the company said it has submitted an Investigational New Drug document, or IND, to the U.S. Food and Drug Administration to obtain final approval for clinical trials on humans.
The company’s gene editing process involves extracting cells from the body, genetically editing the cells in a laboratory, and reinfusing them into the person’s body. Although this requires a hospital or clinic visit and isn’t the more advanced process that Fauci says NIH is now working toward, if successful, it would be the first-ever full cure for HIV through gene therapy.
“We are pleased to see the scientific community backing a strategy American Gene Technologies has been pursuing for many years,” said AGT spokesperson Norman Rogers. “Like the NIH, we believe a cure deliverable to developing nations is a critical goal, especially in the landscape of gene and cell therapy where the efficiencies are more than doubling every year as the costs halve,” he said. “In that environment, anything is possible.”
Gilead Sciences, the drug giant behind the blockbuster HIV prevention pill Truvada, won FDA approval on Thursday to market Descovy — a medication already used by those who have HIV — as its next-generation prevention drug.
Descovy is not yet approved for certain groups, including women who have vaginal sex, since its efficacy has not been studied in this population; for these patients, Truvada is an approved option.
“Descovy for PrEP provides a new HIV prevention option that matches Truvada’s high efficacy with statistically significant improvements in renal and bone safety, which can be an important consideration as people at risk increasingly use PrEP for longer periods of time,” Daniel O’Day, Gilead’s CEO, said in a statement.
Like Truvada, Descovy is taken once daily and can reduce the transmission of HIV by over 95 percent. According to GoodRx, a one month’s supply of Descovy and Truvada both retail for roughly $1,800, though few U.S. patients pay this price as PrEP is covered by private and public insurance.
Gilead has long been buffeted by HIV activists like the PrEP4All coalition over the high price of Truvada and the circumstances of Truvada’s development and testing, which was largely funded by private donors and the U.S. government. That information was first publicized by the Global Health Justice Partnership at Yale University, which wrote “based on our preliminary review, CDC’s Patents for PrEP appear to be valid and enforceable.”
Fewer minority men who are at risk for HIV take a prevention pill or discuss it with their doctors, U.S. researchers say.
Awareness of a pill for “preexposure prophylaxis,” or PrEP, is high for all groups of men who have sex with men. But lower proportions of black and Hispanic men, compared with white men, have actually gotten prescriptions for the drug, which is 99 percent effective at preventing HIV transmission, the study team found.
Based on interviews, researchers found the disparities emerge at the point of having a discussion about PrEP with a healthcare provider. This suggests doctors can do more to help close this gap, they write in the Centers for Disease Control and Prevention’s (CDC) Morbidity and Mortality Weekly Report.
“This type of research is critical to finding – and correcting – missed opportunities to offer PrEP to people at risk for HIV, particularly among African American and Latino gay and bisexual men,” said study leader Dafna Kanny of the CDC’s Division of HIV/AIDS Prevention.
National Gay Men’s HIV/AIDS Awareness Day is September 27. The “Ending the HIV Epidemic” national initiative aims to reduce new infections by 75 percent in five years and by 90 percent in 10 years.
“It’s important for providers to take sexual histories of gay and bisexual men and to discuss PrEP as an option for HIV prevention with those who could potentially benefit from it,” Kanny told Reuters Health by email. “These discussions also help to destigmatize PrEP use, which is particularly important for increasing PrEP use among African American and bisexual men.”
Kanny’s team analyzed interviews with more than 4,000 men who participated in the 2017 National HIV Behavioral Surveillance survey to understand who is using PrEP and why some are not using it.
Candidates for PrEP use include men with multiple male sex partners in the past year, a male sex partner with an HIV infection during the past year, condomless anal sex or a bacterial sexually-transmitted infection within the past year.
Overall, 95 percent of the white men in the study said they were aware of PrEP, along with 87 percent of Hispanic men and 86 percent of black men. Yet only 58 percent of whites, 44 percent of Hispanics and 43 percent of blacks said they discussed PrEP with a clinician in the past year.
About 42 percent of white men, 30 percent of Hispanic men and 26 percent of black men reported taking PrEP in the past year.
Among the steps from awareness to getting onto PrEP, discussing it with a healthcare provider seemed pivotal. Men who got that far were more likely to be using PrEP. Still, disparities remained. Among the 2,000 men who discussed PrEP with a clinician, 68 percent of white men reported PrEP use, compared with 62 percent of Hispanic men and 55 percent of black men.
These differences were not explained by a lack of insurance or a usual source of health care – typical barriers to accessing prescription medications.
Geographically, disparities in PrEP use were seen between white and black men in the South and West, and between white and Hispanic men in the South.
The CDC estimates that less than 25 percent of the more than 1 million Americans who could benefit from PrEP are using it, Kanny said. She added, “There is a critical need to address racial and ethnic disparities.”
Future studies will need to investigate other barriers to PrEP use, such as high deductibles and high co-pays, which affect racial and ethnic minorities in particular, said Brandon Marshall of the Brown University School of Public Health in Providence, Rhode Island, who wasn’t involved in the CDC study.
“If we continue to see these disparities, HIV infections will likely continue to grow,” he told Reuters Health by phone. “Our goals to end the epidemic will be out of our grasp.”
Recent research indicates that some doctors don’t prescribe PrEP because they believe it will lead to risky sexual behavior, Marshall noted, which may disproportionately affect racial and ethnic minority men.
“These race-based stereotypes held by some providers also continue to perpetuate mistrust of the medical community in racial/ethnic minority communities,” he said. “If you feel your healthcare provider isn’t listening to you or not addressing your needs, it’s time to find a different provider who has more experience with PrEP and can answer your questions.”
Every year, the San Francisco Department of Public Health (SFDPH) publishes a comprehensive report on HIV incidence and prevalence in the city, showing HIV trends to guide the public health response. Continuing a downward trend since the peak of the HIV epidemic in the 1990s, the most recent report with 2018 data shares a historic milestone reached by the city: Fewer than 200 HIV diagnoses occurred in San Francisco.
A total of 197 people were diagnosed with HIV last year in San Francisco. This is a 13% decline from 227 diagnoses made in 2017, and a 62% decline from 523 infections ten years ago in 2008. The peak number of HIV diagnoses in San Francisco occurred in 1992 with 2,327 diagnoses.
Most people (94%) living with HIV are aware of their status, and 91% of people newly diagnosed with HIV in 2018 entered care within one month. It is estimated that 74% of people with a last known address in San Francisco who are living with HIV were virally suppressed in 2017.
“I am really delighted that we in San Francisco, since the 1980s, have been at the forefront of pushing for innovative ways to change policies, new sciences and technologies to help us get to this milestone,” said Mayor London Breed at a press conference at Zuckerberg San Francisco General’s Ward 86. “This shows that when we work together with the community, with our policy makers, with our public health experts, and our nonprofits we can make a difference and save people’s lives.”
“We are pleased, but not satisfied,” said Diane Havlir, MD, who spoke on behalf of the Getting to Zero consortium. “We’re not satisfied because we had nearly 200 new diagnoses of HIV in our city—and it’s a preventable disease.”
Differences by Race and Ethnicity, Housing Status and for People who Inject Drugs
People of color, people experiencing homelessness and people who inject drugs continue to experience higher diagnosis rates, lower viral suppression rates and lower survival rates.
People of color are disproportionately affected by HIV
African American and Latinx men had the highest diagnosis rates (145 and 89 per 100,000), and rates increased from previous years. Diagnosis rates for white men have declined steadily since 2012. Among women, African Americans had a much higher diagnosis rate (35 per 100,000) than women of other races.
Overall, 74% of people living with HIV in San Francisco were virally suppressed, while viral suppression rates were lower for African Americans (68%), trans women (68%), women (66%), people who use injection drugs (65%), men who have sex with men who inject drugs (68%) and trans women who inject drugs (64%).
“San Francisco continues to make unprecedented progress towards ending the HIV epidemic,” said Joe Hollendoner, CEO of San Francisco AIDS Foundation. “However, we continue to see racial disparities related to HIV health outcomes. To end HIV transmission and AIDS-related deaths, the public health system needs to address the systemic racism that is inhibiting our progress.”
“We have to double down on these gaps that we’re seeing,” said Havlir. “We need to listen, and we need to deploy new innovative approaches with tools that have. With PrEP. And with upcoming tools like long-acting injectable [HIV] therapies which could make it a lot easier for some of our populations.”
Homelessness compounds HIV risk and severity of health outcomes
As the number of new HIV diagnoses shrinks year after year in San Francisco, and the number of people experiencing homelessness grows, a higher proportion of HIV diagnoses are occurring among people without access to medical care, social support and prevention resources—in particular people without housing.
In 2018, 20% (40) of new HIV diagnoses were among people without housing compared to 10% (29) in 2015. There were 8,011 people experiencing homelessness in San Francisco in January 2019, according to the 2019 San Francisco Homeless Point-in-Time Count and Survey, a 14% increase since 2013.
People without housing are also much less likely to be virally suppressed. Only 33% of people experiencing homelessness were virally suppressed, compared to 74% of people overall.
“We know that many elements that are key to success, for people living with HIV, are challenging if you don’t have a place to live,” said Monica Ghandi, MD, MPH, medical director of the SFGH HIV clinic. “That would be like making and keeping appointments. Where you store your medications, and where you keep them safe. Maintaining safe sex, and healthy eating. All of these barriers to taking your medications every day are amplified 100-fold if you don’t have a home.”
“Our focus on disparities really has to focus on ensuring that we reach people where they are,” said Hyman Scott, MD, MPH from Bridge HIV at SFDPH. “There are no ‘hard to reach’ populations—there are just ‘hard to deliver’ services. We need to re-think the way we approach some of these services that we deliver.”
HIV and people who inject drugs
People who inject drugs account for 25% of new HIV diagnoses, (10% are men who have sex with men who inject drugs; 1% are trans women who inject drugs; 14% are other people who inject drugs), a proportion which has risen over the years.
In addition to accounting for a higher proportion of HIV diagnoses, injection drug use is associated with worse health outcomes: People who inject drugs are less likely to be virally suppressed and have lower three-year survival rates after an AIDS diagnosis.
The percentage of people who are diagnosed with HIV who inject drugs is rising steadily every year, while reductions are seen in other populations including men who have sex with men.
“San Francisco has a robust syringe access program, which has kept HIV transmission rates low among people who inject drugs, but it’s not sufficient to eliminate HIV transmission among people who inject,” said Laura Thomas, director of harm reduction policy at San Francisco AIDS Foundation. “Housing instability and displacement make it challenging for people who use substances to always do so safely. That’s why it’s so important for us to establish safe injection sites in our city.”
“Unless we invest in expanding low barrier substance use and mental health counseling services like those offered at our Harm Reduction Center and at the Stonewall Project, I worry that increased HIV infection trends like those we’re seeing with people who inject drugs will continue,” said Mike Discepola, MA, senior director of behavioral health services and the Stonewall Project at San Francisco AIDS Foundation. “We will not get to zero new infections in San Francisco unless we focus services on our most vulnerable populations. This includes those who inject and use drugs, are experiencing homelessness or have untreated mental health concerns.”
An Aging HIV Population
With nearly 16,000 people living with HIV in San Francisco, two-thirds (10,691 people) are age 50 and older.
“We know that this is the generation that didn’t plan to live,” said Vince Crisostomo, manager of theElizabeth Taylor 50-Plus Network at San Francisco AIDS Foundation. “They didn’t plan financially, they didn’t set up 401Ks. But, they did live. And service providers need to be thinking about how to adjust services to meet the needs of these long-term survivors. How can we provide culturally competent services for people of older age who are living with HIV?”
“To end the epidemic we cannot leave anyone behind,” said Hollendoner. “We must achieve this ambitious goal together and prove to the world that it can be done.”
Guided by a new 5-year strategic plan, San Francisco AIDS Foundation charts a course for improving the sexual health outcomes of people of color and other priority communities, establishing safe injection sites, creating a comprehensive network of health and wellness services for people over age 50 who are living with HIV, and living our values of racial justice.
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.
Publication of the largest-ever study of the roles of genes in homosexual behavior is fanning the debate over whether being gay is due to genes or environment.
“There is no ‘gay gene’ that determines whether someone has same-sex partners,” says Andrea Ganna, a geneticist at the Broad Institute of MIT and Harvard and the University of Helsinki.
Family studies have suggested that genetics account for about 32 percent of heritability of homosexual behavior. But each SNP, or single nucleotide polymorphism, has a very small effect on whether someone has ever had a same-sex sexual partner, the new research found.
Taking into account all the SNPs measured in the study, including those that weren’t statistically significantly associated with same-sex behavior, explained only 8 to 25 percent of heritability of same-sex behavior. When considering just those five statistically significant SNPs, that number drops to much less than 1 percent.
But those variants could point to biological processes that are involved in choosing sex partners, the researchers say. For instance, one variant identified in the study has been linked to male-pattern baldness, and another to the ability to smell certain chemicals, which may affect sexual attraction.
“The study is a big step forward because of its huge size,” says J. Michael Bailey, a psychologist at Northwestern University in Evanston, Ill., who has worked on sexual orientation genetics but was not involved in the work. It included more than 470,000 people, dwarfing previous research.
“This is the first study that we can be pretty sure that they’ve identified genetic variants associated with an aspect of same-sex behavior,” Bailey says. “I’ve been a coauthor on some previous molecular genetic studies that were much more tenuous. I believe these results will replicate.”
But Bailey disagrees with some of the study’s conclusions. For instance, Ganna says that people who have exclusively same-sex or exclusively opposite-sex partners are genetically distinct from people who have partners of both sexes. That means that sexuality may not be a continuum from completely heterosexual to homosexual after all. So the Kinsey scale, which scores people’s sexual behavior along a spectrum with bisexuality in the middle, may need to be rethought, the researchers say.
But the Kinsey scale accurately predicts men’s arousal when shown erotic pictures of either men or women, Bailey says. That makes it a far better tool than the genetic score for predicting sexual preference, he says.
Qazi Rahman, a psychologist and sexual orientation researcher at King’s College London, has bigger quibbles with the study. “I should be really excited about this,” he says. But “despite being an ardent believer in the biological basis of sexuality, I’ve found this study problematic, and I’m not at all sure what was found and whether that holds up.”
Rahman points to what he sees as inconsistencies in the data and possible bias in the people who volunteered to participate in the study. The study drew volunteers from two big genetic databases, the UK Biobank and the consumer DNA testing company 23andMe, and from three smaller studies. Participants answered questionnaires about how many sexual partners of each sex they had ever had. 23andMe customers also responded to questions about attraction, sexual identity and fantasies.
But only 5.5 percent of UK Biobank participants and about 1.5 percent of 23andMe’s customers joined the study. Such low participation rates could skew the results, or point to genetic variants that make people more likely to sign up for a study. “What you’re getting is genetic influences on self-selection into a study, not genetic influences on same-sex behavior,” Rahman says.
It’s legitimate to question where study participants come from, but there’s no way to know whether that bias is affecting the results, says coauthor Benjamin Neale, a geneticist at Massachusetts General Hospital in Boston and the Broad Institute.
The study wasn’t designed to address sexual orientation or identity, but the same variants associated with same-sex behavior were also associated in 23andMe participants with attraction, sexual identity and fantasies. The small contribution of genetics to sexual behavior is in line with genetic contributions to other behaviors, such as level of education attainment. “There’s a lot of room for nongenetic effects,” Bailey says.
The authors don’t disagree. The study underscores that elements of both biology and one’s environment may play roles in shaping sexual behavior, Neale says. Environmental influences may include an array of developmental, social and cultural factors that all could affect behavior, he says.
That’s true, says coauthor J. Fah Sathirapongsasuti, a computational biologist at 23andMe in Mountain View, Calif. But, he says, “just because something is not completely genetic or something has an environmental, or what we call nongenetic, component doesn’t mean it’s a choice.”
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.
“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.
Kyle Murphy, the communications director for the national AIDS advocacy group AIDS United, released to a listserv of AIDS activists a letter informing AIDS United’s president and CEO and other officials and staff members that he was resigning from his job because the group accepts large sums of money from pharmaceutical companies.
Murphy states in his Aug. 9 letter, a copy of which was obtained by the Washington Blade, that AIDS United is among nearly all of the nation’s AIDS advocacy organizations that for years have worked for the interests of people with HIV/AIDS who accept money from drug companies.
He said that although he does not think any of the groups and their leaders have compromised their basic principles and objectives for fighting AIDS, the widespread contributions by the nation’s largest pharmaceutical companies to AIDS organizations gives the appearance of a conflict of interest, even if no compromises have been made.
“This decision was not made lightly, and I hope that all of you will believe that the primary source of my anguish the last several months was the inspiration and kindship that I feel for each of you,” he said in his letter. “I am an AIDS United constituent. I am a gay man. I am also living with HIV,” he wrote.
“You are my heroes, and I have been so inspired by each and every one of you, and the call to end this epidemic,” he said. “But when it all is said and done, the mission of our constituents are what matter and we are not serving like we should,” he states in his letter.
“Not out of some malevolence. But rather, our collective hearts wrote a check, that our budgets couldn’t cash,” his letter continues. “And so with the best of intentions and the sincere desire to be good partners with our colleagues in both the public and private sector, we have been slowly bought off. And most of us know it. We just aren’t willing to say it,” Murphy says in his letter.
As one example of a possible conflict of interest, Murphy points out how most AIDS organizations and the “vast majority” of the HIV community have become strong supporters of the HIV prevention regimen known as PrEP in which the drug Truvada, manufactured by pharmaceutic giant Gilead Sciences, is widely used and promoted.
“This support may or may not have been related to the sizeable donations that Gilead Sciences makes to almost every single HIV service provider, advocacy organization and patient interest group in the country,” Murphy states in his letter. “But the mere fact that this potential and glaring conflict of interest exists, should be enough to give all of us pause,” he wrote.
“I cannot say that Gilead Sciences or any other pharmaceutical company has inappropriately influenced any decision that the leadership of AIDS United or any of its many partners have made,” Murphy states in his letter. “But I do know that their status as a contributor is a consideration when we decide how to respond to questions around drug pricing, PrEP access, and drug safety,” he wrote.
“And that alone is enough for me to decide that I can no longer work for an organization that has representatives from these companies on its board,” Murphy stated.
William McColl, AIDS United’s Vice President for Policy and Advocacy, sent an email message to the listserv members who received Murphy’s letter, giving what he said was background information on some of the issues raised by Murphy.
“We greatly respect Kyle and wish him the best in his future,” McColl said in his message.
McColl noted that pharmaceutical company representatives have served on AIDS United’s board “dating back more than 30 years” and currently include representatives from Gilead Sciences and the pharmaceutical company ViiV Healthcare. He said approximately 24 percent of AIDS United’s fiscal year 2018-2019 budgets of more than $16 million are funded by pharmaceutical companies.
“Virtually all of this funding supports grants directly to organizations supporting people living with HIV,” McColl said in his message. “We seek to engage with funders (including pharmaceutical partners) precisely because it helps us to bring additional financial resources to the most difficult issues and underserved populations in the HIV epidemic; sometimes where funding might otherwise not be available,” he states in his email message.
“Our mission to end the HIV epidemic in the U.S. and serve our constituents is front and center with any decision we make as to an organization and we will consider opportunities to partner, including with pharmaceutical companies, where it advances this mission,” he wrote. “AIDS United has been and will continue to be transparent about the sources of its funding, which is publicly available information.”
Jesse Milan Jr., AIDS United’s president and CEO, told the Blade in a separate statement that the organization has included people on its board from a wide range of “stakeholders,” including funders.
“AIDS United engages with a wide spectrum of donors, including pharmaceutical funders, to support our grant-making, policy and advocacy, and capacity building work,” Milan said. “Their commitment makes much that we do possible, including funding many of our grants that support the work of hundreds of community organizations each year.”