FDA Approves Long-Acting Injectable Drug for HIV Prevention

Approval Marks Pivotal Expansion of HIV Prevention Options in the United States

The U.S. Food and Drug Administration has announced its first approval of a long-acting HIV prevention medication, marking a pivotal expansion of HIV prevention options in the United States.

Developed by ViiV Healthcare, the medicine is long-acting cabotegravir injected once every two months. FDA has approved the medicine for use by adults and adolescents weighing at least 35 kilograms who are at risk of sexually acquiring HIV. This milestone marks a vital expansion of biomedical HIV prevention options available to people in the United States. The National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health, thanks and congratulates everyone who led, conducted and participated in the research that led to this important development.

An estimated 34,800 people in the United States acquired HIV in 2019, the most recent year for which data are available. Men who have sex with men, transgender women who have sex with men, and Black cisgender women are among those disproportionately affected by HIV in this country.

Until today, the only FDA-licensed medications for HIV pre-exposure prophylaxis (PrEP) were daily oral pills containing the HIV drugs tenofovir and emtricitabine. These medications are highly effective at preventing HIV when taken daily as prescribed. However, taking a pill daily while feeling healthy can be challenging. Long-acting injectable cabotegravir PrEP is a less frequent, more discreet HIV prevention option that may be more desirable for some people. 

The FDA approval is based on data primarily from two NIH-supported clinical trials, HPTN 083 and HPTN 084. Both trials compared the safety and effectiveness of a PrEP regimen containing long-acting injectable cabotegravir with a regimen of daily oral PrEP. HPTN 083 enrolled more than 4,500 cisgender men who have sex with men and transgender women who have sex with men in Argentina, Brazil, Peru, South Africa, Thailand, the United States and Vietnam. HPTN 084 enrolled more than 3,200 cisgender women in Botswana, Eswatini, Kenya, Malawi, South Africa, Uganda and Zimbabwe. The two trials found that both HIV prevention methods were safe and highly effective, but injectable cabotegravir was more effective than daily oral PrEP at preventing HIV acquisition. 

The HPTN 083 and HPTN 084 trials were sponsored by NIAID and conducted by the NIH-funded HIV Prevention Trials Network (HPTN). NIAID and ViiV Healthcare co-funded both trials; the Bill & Melinda Gates Foundation also supported HPTN 084. HPTN is co-funded by NIAID, the National Institute of Mental Health, the National Institute on Drug Abuse, and the Eunice Kennedy Shriver National Institute of Child Health and Human Development, all part of NIH.

NIH study offers new evidence of early SARS-CoV-2 infections in U.S.

A new antibody testing study examining samples originally collected through the National Institutes of Health’s All of Us Research Program found evidence of SARS-CoV-2 infections in five states earlier than had initially been reported. These findings were published in the journal Clinical Infectious Diseases. The results expand on findings from a Centers for Disease Control and Prevention study(link is external) that suggested SARS-CoV-2, the virus that causes COVID-19, was present in the U.S. as far back as December 2019.

In the All of Us study, researchers analyzed more than 24,000 stored blood samples contributed by program participants across all 50 states between Jan. 2 and March 18, 2020. Researchers detected antibodies against SARS-CoV-2 using two different serology tests in nine participants’ samples. These participants were from outside the major urban hotspots of Seattle and New York City, believed to be key points of entry of the virus in the U.S. The positive samples came as early as Jan. 7 from participants in Illinois, Massachusetts, Mississippi, Pennsylvania and Wisconsin. Most positive samples were collected prior to the first reported cases in those states, demonstrating the importance of expanding testing as quickly as possible in an epidemic setting.

“This study allows us to uncover more information about the beginning of the U.S. epidemic and highlights the real-world value of longitudinal research in understanding dynamics of emerging diseases like COVID-19,” said Josh Denny, M.D., M.S., chief executive officer of All of Us and an author of the study. “Our participants come from diverse communities across the U.S. and give generously of themselves to drive a wide range of biomedical discoveries, which are vital for informing public health strategies and preparedness.”

In studies like these, false positives are a concern, particularly when the prevalence of viral infections is low, as was the case in the early days of the U.S. epidemic. Researchers in this study followed CDC guidance to use sequential testing on two separate platforms to minimize false positive results.

All of Us worked with Quest Diagnostics to test samples on the Abbott Architect SARS-CoV-2 IgG ELISA and the EUROIMMUN SARS-CoV-2 ELISA (IgG) platforms. For a sample to be considered “positive” by the research team, it had to have positive results on both platforms, which target antibodies that bind to different parts of the virus. Both tests have emergency use authorization from the FDA.

“Antibody testing of blood samples helps us better understand the spread of SARS-CoV-2 in the U.S. in the early days of the U.S. epidemic, when testing was restricted and public health officials could not see that the virus had already spread outside of recognized initial points of entry,” said Keri N. Althoff, Ph.D., lead author and associate professor of epidemiology at the Johns Hopkins Bloomberg School of Public Health, Baltimore. “This study also demonstrates the importance of using multiple serology platforms, as recommended by the CDC.”

Antibodies are proteins produced in the blood in response to an infection, such as a virus. They play a critical role in fighting infections and are helpful signs that a person may have been exposed to an infection in the past, even if they didn’t show symptoms. In the All of Us study, researchers looked in participant samples for a type of antibodies called IgG. These antibodies do not appear until about two weeks after a person has been infected, indicating that participants with these antibodies were exposed to the virus at least several weeks before their sample was taken. In this study, the first positive samples came from participants in Illinois and Massachusetts on Jan. 7 and 8, 2020, respectively, suggesting that the virus was present in those states in late December.

The study authors noted several limitations to their study. While the study included samples from across the U.S., the number of samples from many states was low. In addition, the authors do not know whether the participants with positive samples became infected during travel or while in their own communities. Ideally, this study could be replicated in other populations with samples collected in the initial months of the U.S. epidemic and with multiple testing platforms to compare results.

All of Us expects to release more information following further analysis, and will offer participants whose samples were included in the study an opportunity to receive their individual results. The presence of antibodies in one’s blood sample does not guarantee that a person is protected from the infection (has immunity), or that any such protection will last.

U.S. clinical trial results show Novavax vaccine is safe and prevents COVID-19

Results from a Phase 3 clinical trial enrolling 29,960 adult volunteers in the United States and Mexico show that the investigational vaccine known as NVX-CoV2373 demonstrated 90.4% efficacy in preventing symptomatic COVID-19 disease.

The candidate showed 100% protection against moderate and severe disease. In people at high risk of developing complications from COVID-19 (people 65 years or older and people under age 65 with certain comorbidities or with likely regular exposure to COVID-19), the vaccine showed 91.0% efficacy in preventing symptomatic COVID-19 disease.

Safety data indicate the investigational vaccine was generally well-tolerated. Mild-to-moderate injection site pain and tenderness were the most common local symptoms among participants, and fatigue, headache and muscle pain lasting less than two days were the most common systemic symptoms.

Novavax, Inc., of Gaithersburg, Maryland, developed the investigational vaccine and led the clinical trial known as PREVENT-19(link is external). The Biomedical Advanced Research and Development Authority (BARDA), a component of the HHS Office of the Assistant Secretary for Preparedness and Response, and the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health, provided funding support for the trial as part of the federal COVID-19 response.

The PREVENT-19 trial began in late December 2020 and enrolled adult volunteers at 119 study sites, including those in the NIAID-supported COVID-19 Prevention Network (CoVPN)(link is external). Participants were randomly assigned to receive two shots, 21 days apart, of either the investigational vaccine or a saline placebo. Randomization occurred in a 2:1 ratio with two volunteers receiving NVX-CoV2373 for each one who received placebo. Because the trial was blinded, neither investigators nor participants knew who received the candidate vaccine.

PREVENT-19 was designed to evaluate whether NVX-CoV2373 can prevent symptomatic COVID-19 disease seven or more days after the second injection relative to placebo. The results shared today are based on 77 cases of symptomatic COVID-19 that investigators observed among trial participants from January 25 through April 30, 2021. Investigators recorded 63 cases among the approximately 10,000 participants who received placebo and 14 cases among the approximately 20,000 participants who received the investigational vaccine. Of the 63 COVID-19 cases in the placebo group, investigators classified 10 as moderate and four as severe. There were no cases of moderate or severe disease in the investigational vaccine group.

NVX-CoV2373 is a subunit vaccine made from a stabilized form of the coronavirus spike protein using the company’s recombinant protein nanoparticle technology. The purified protein antigens in the vaccine cannot replicate or cause COVID-19. The vaccine also contains a proprietary adjuvant, MatrixM™. Adjuvants are additives that enhance desired immune system responses to vaccine. NVX-CoV2373 is administered by injection in liquid form and can be stored, handled and distributed at above-freezing temperatures (35° to 46°F.) A single vaccine dose contains 5 micrograms (mcg) of protein and 50 mcg of adjuvant. The vaccine is administered as two intramuscular injections 21 days apart. The technology used for this vaccine was developed under a long-standing contract with the Department of Defense.

African Americans who smoke seem at higher risk of coronary heart disease

African Americans who smoke appear to have more than twice this risk of  developing coronary heart disease compared to those who do not smoke, a new study has found. The findings — the first up-close look at the relationship between smoking and coronary heart disease in this population—also examined the risk for plaque buildup in the arteries of African Americans who smoke. Excessive plaque in the arteries is a known predictor of heart attacks and heart failure.    

 The study, published today in the Journalof the American Heart Association, draws on data from nearly 4,500 participants in the Jackson Heart Study, the largest cohort study investigating cardiovascular disease exclusively in African Americans. That study, as well as the new research, is supported by the National Heart, Lung, and Blood Institute (NHLBI), and the National Institute of Minority Health and Health Disparities (NIMHD), both part of the National Institutes of Health.    

Coronary heart disease, the leading cause of death in the world, is the most common type of heart disease. In the United States, it affects more than 20 million adults(link is external) and causes one in seven deaths, according to the Centers for Disease Control and Prevention. It can develop when plaques build up in the blood vessels that supply the heart. These clogged, or calcified, arteries can limit or block blood flow and increase the risk for heart attack.    

Compared to whites, African Americans are more likely to die from coronary heart disease. Cigarette smoking causes inflammation and atherosclerosis, and coronary heart disease. Despite a marked decline in smoking among African American adults in recent years, almost 15% reported current cigarette smoking in 2019. Yet the link between cigarette smoking and coronary heart disease has been understudied in this population.    

African Americans have disproportionally higher rates of hypertension, diabetes, and obesity—known risk factors that partly explain the greater death toll from coronary heart disease in this community, according to the researchers.    

“But smoking is also a well-documented risk factor, which, combined with the others, suggest that African Americans smokers represent a particularly vulnerable population for this disease,” said lead study author Adebamike Oshunbade, M.D., M.P.H., a postdoctoral research fellow at the University of Mississippi Medical Center in Jackson. “However, our study is the first to focus on the relationship between cigarette smoking and coronary heart disease exclusively among a large cohort of African Americans.”      

Given the scant inclusion of African Americans in prior studies, researchers had limited ability to single out the specific effects of smoking, distinct from other risk factors, in this population. But with the Jackson Heart Study cohort of 5,306 participants, Oshunbade and colleagues were able to assess the relationship between smoking, coronary heart disease, and coronary artery calcification in African American adults.   

The investigators used coronary artery calcification (CAC) score measurements to assess the degree of calcified plaque buildup in participants’ coronary arteries. CAC score, which is measured by a CT scan, is a key predictor of an individual’s risk for cardiac events like heart attacks.      

For the study, 4,432 participants without a history of coronary heart disease at the time (2000-2004), were classified as current smokers, former smokers, or never smokers. After taking into account other risk factors — including smoking intensity, or the number of cigarettes each consumed daily — researchers followed the participants through 2016, tracking the development of coronary heart disease.     

The researchers found that, compared to those who never smoked, those who currently smoked had a more than two-fold higher risk of coronary heart disease. Similarly, those who smoke had an increased likelihood of having a higher CAC score.   

   “Smoking is a modifiable risk factor for cardiovascular disease and 73% of African American adults who smoke want to quit,” said David Goff, M.D., Ph.D., director of the NHLBI’s Division of Cardiovascular Sciences. “However, compared to whites, African American patients are less likely to receive information about smoking cessation treatments that we know can make a difference. Fully addressing tobacco-related disparities requires addressing conditions where people live, work, and play.” 

As the authors noted, the study was observational, and the findings do not establish casual links. Additionally, they should not be generalized to people of other races or regions.

NIH funds study to evaluate remdesivir for COVID-19 in pregnancy

A new study funded by the National Institutes of Health will evaluate the effects of remdesivir in pregnant women who have been prescribed the drug to treat COVID-19. The study, which will be conducted at 17 sites in the continental United States and Puerto Rico, aims to determine how pregnant women metabolize the drug and whether there are any potential side effects.

“Pregnant women with COVID-19 are at high risk for hospitalization, for intensive care admission and for needing ventilator support,” said Diana W. Bianchi, M.D., director of NIH’s Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD). “There is an urgent need to identify effective treatments for this population and to determine whether drugs prescribed for other adults are appropriate for use in pregnancy.”

The study is funded by NICHD, the National Institute of Allergy and Infectious Diseases (NIAID), and the National Institute of Mental Health, all part of NIH. Called IMPAACT 2032, the study will be conducted by the NIH-funded International Maternal Pediatric Adolescent AIDS Clinical Trials (IMPAACT) Network.

Originally developed to treat Ebola and Marburg virus infections, remdesivir was shown in a NIAID-funded clinical trial to accelerate recovery in patients with advanced COVID-19 disease. Remdesivir has since been approved by the U.S. Food and Drug Administration for the treatment(link is external) of COVID-19 in adults and children over age 12 years.

Although it has not been approved specifically for use in pregnancy, remdesivir can be prescribed to pregnant women if their physicians believe the drug may benefit them. However, physicians currently lack scientific evidence for the safety and efficacy of remdesivir for treating pregnant women with COVID-19. Because pregnancy may influence a drug’s effects, IMPAACT 2032 will compare remdesivir use in pregnant and non-pregnant women of reproductive age who are hospitalized with COVID-19.

The study will evaluate remdesivir’s pharmacokinetics—how a drug is absorbed, moves through the body and is broken down and eliminated in pregnant women and nonpregnant women of childbearing potential who receive it as part of clinical care. For women who received the drug within five days of delivery, samples from the plasma and umbilical cord will be analyzed for insight into remdesivir’s pharmacokinetics in the placenta. Breast milk will also be tested for remdesivir among women who are lactating. Researchers will also document potential side effects and adverse events that could occur with use of the drug.

US decision will provide ‘profound relief’ to millions in war-torn Yemen: UN spokesperson

OCHA/Mahmoud Fadel
An internally displaced child plays at an IDP settlement in Al-Dhale’e governorate, southern Yemen.

The US announcement revoking the previous administration’s terrorist designation of Yemen’s Houthi movement, formally known as Ansar Allah, will provide “profound relief” to millions in the country, who depend on international assistance and imports for their survival, the UN Spokesperson said on Saturday. 

In a note to correspondents, Stéphane Dujarric, Spokesman for the UN Secretary-General, welcomed the announcement, which was made by the Biden administration on Friday. 

“The revocation of the designations will provide profound relief to millions of Yemenis who rely on humanitarian assistance and commercial imports to meet their basic survival needs. It will help ensure that much-needed essential goods reach them without significant delays”, Mr. Dujarric said. 

“At a time when Yemen is at significant risk of famine, maintaining commercial imports and humanitarian assistance in adequate quantities is essential”, he added. 

Mr. Dujarric also expressed hope that the move will contribute to UN efforts to resume a Yemeni-led and Yemeni-owned political process to reach an inclusive, negotiated settlement to the conflict. 

Methamphetamine overdose deaths rise sharply nationwide

NIH-supported study finds biggest increase among American Indians and Alaska Natives.

Non-Hispanic American Indians and Alaska Natives: Overdose deaths involving methamphetamine rose from 4.5 to 20.9 per 100,000 people ages 25 to 54 during 2011-2018. NIDA

Methamphetamine overdose deaths surged in an eight-year period in the United States, according to a study that will published today in JAMA Psychiatry. 

The analysis revealed rapid rises across all racial and ethnic groups, but American Indians and Alaska Natives had the highest death rates overall. The research was conducted at the National Institute on Drug Abuse (NIDA), part of the National Institutes of Health.

Deaths involving methamphetamines more than quadrupled among non-Hispanic American Indians and Alaska Natives from 2011-2018 (from 4.5 to 20.9 per 100,000 people) overall, with sharp increases for both men (from 5.6 to 26.4 per 100,000 from 2011-2018) and women (from 3.6 to 15.6 per 100,000 from 2012-2018) in that group. The findings highlight the urgent need to develop culturally tailored, gender-specific prevention and treatment strategies for methamphetamine use disorder to meet the unique needs of those who are most vulnerable to the growing overdose crisis. Long-term decreased access to education, high rates of poverty and discrimination in the delivery of health services are among factors thought to contribute to health disparities(link is external) for American Indians and Alaska Natives.

“While much attention is focused on the opioid crisis, a methamphetamine crisis has been quietly, but actively, gaining steam—particularly among American Indians and Alaska Natives, who are disproportionately affected by a number of health conditions,” said Nora D. Volkow, M.D., NIDA director and a senior author of the study. “American Indian and Alaska Native populations experience structural disadvantages but have cultural strengths that can be leveraged to prevent methamphetamine use and improve health outcomes for those living with addiction.”

Shared decision-making between patient and health care provider and a holistic approach to wellness are deeply rooted traditions among some American Indian and Alaska Native groups and exist in the Indian health care system. Traditional practices, such as talking circles, in which all members of a group can provide an uninterrupted perspective, and ceremonies, such as smudging, have been integrated into the health practices of many Tribal communities. Leveraging traditions may offer a unique and culturally resonant way to promote resilience to help prevent drug use among young people. Development and implementation of other culturally appropriate and community-based prevention; targeting youth and families with positive early intervention strategies; and provider and community education may also aid prevention efforts among this population.

The study found markedly high death rates among non-Hispanic American Indians and Alaska Natives, as well as a pattern of higher overdose death rates in men compared to women within each racial/ethnic group. However, non-Hispanic American Indian and Alaska Native women had higher rates than non-Hispanic Black, Asian, or Hispanic men during 2012-2018, underscoring the exceptionally high overdose rates in American Indian and Alaska Native populations. The results also revealed that non-Hispanic Blacks had the sharpest increases in overdose death rates during 2011-2018. This represents a worrying trend in a group that had previously experienced very low rates of methamphetamine overdose deaths.

Methamphetamine use is linked to a range of serious health risks, including overdose deaths. Unlike for opioids, there are currently no FDA-approved medications for treating methamphetamine use disorder or reversing overdoses. However, behavioral therapies such as contingency management therapy can be effective in reducing harms associated with use of the drug, and a recent clinical trial reported significant therapeutic benefits with the combination of naltrexone with bupropion in patients with methamphetamine use disorders.