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Yale has been awarded over $3.7 million to strengthen systems of care for people with opioid disorder and at risk for HIV across five states.

The new initiative, called Project MO(H)RE (Multisite Opioid (& HIV) Response Endeavor), will increase medication-assisted treatments for opioid-use disorder, strengthen networks, and better coordinate care. The project will focus on patients with or at risk for HIV and Hepatitis C (HCV). The award is part of the Health Resources and Services Administration’s “Special Projects of National Significance” program.

The project will be led by Frederick L. Altice, M.D., professor of medicine and public health at Yale, a pioneer in developing and integrating collaborative models of treatment for infectious diseases and substance use disorders. He and his expert team will work across multiple stakeholder groups and disparate geographic regions to design creative solutions to the opioid crisis. Altice is joined by two Yale researchers: Merceditas Villanueva, M.D., associate professor and director of the AIDS Program, and Lynn Madden, CEO of the nonprofit APT Foundation, a nonprofit healthcare organization that specializes in integrated treatment of substance use disorders.

Altice said that “timing for this implementation science project could not be more crucial as the opioid epidemic continues to claim lives with parallel outbreaks of HIV and HCV. This project will help guide multi-level stakeholders within states to focus on scaling up treatment for opioid use disorders, the most effective strategy to reduce overdose and transmission of blood-borne infections.”

Over a period of three years, Yale will coordinate activities with five participating states — Kentucky, West Virginia, Connecticut, Vermont, and New Hampshire — that are either disproportionately impacted by HIV or have recently been designated high-vulnerability regions for outbreaks of HIV and HCV related to opioid use. For example, West Virginia has the highest rate of opioid-related deaths nationally and is now experiencing unprecedented HIV outbreaks in some counties.

Robert Hansen, director of West Virginia’s Office of Drug Control Policy, said: “Building upon our ongoing efforts to address HIV cases resulting from the opioid epidemic is a critical piece of West Virginia’s Substance Use Response Plan. We are excited to have this opportunity to better align our programs to achieve the best possible outcomes.”

Other leaders in Project MO(H)RE include Alice Thornton, M.D., chief of infectious disease at the University of Kentucky, and Daniel Daltry, program chief of the HIV, STD, and Hepatitis C program at the Vermont Department of Health. “This initiative is especially important in Kentucky as the commonwealth has been hit extremely hard by the opioid epidemic,” said Thornton. “We are eager to participate in a project that will better coordinate HIV and opioid treatment services.” He added: “Vermont has made great strides to scale up treatments for opioid-use disorder, yet this project provides new opportunities to better integrate HIV services for those in treatment.”

The team’s first task will be to assess the legal and financial landscapes for increased and improved addiction treatment. They will meet with state and system stakeholders to review the gaps, opportunities, and priorities for scaling up treatment and coordinating services. Subsequently, a team of implementation specialists will facilitate rapid-cycle projects (projects made and tested in three months or less) on addiction treatment scale-up. Project MO(H)RE is modeled on a process developed by the Institute for Healthcare Improvement that helps organizations achieve “breakthrough” improvements in quality medical treatment. 

Additional team members include Kimberly Johnson from University of South Florida, who will guide the epidemiological and regulatory gap analysis, and Jennifer Oliva from Seton Hall University, who will oversee the legal components of the project. Altice and his team will lead efforts carried out across the country. “States are thrilled to bring together public health and behavioral health constituencies and key stakeholders, who are not often at the same table, to work together to solve common and related challenges,” he said.

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Tuberculosis and HIV—two of the world’s deadliest infectious diseases—are far worse when they occur together. Now, Texas Biomedical Research Institute researchers have pinpointed an important mechanism at work in this troubling health problem. And, their discovery could lead to a new mode of treatment for people at risk. The results were published in the Journal of Clinical Investigation, a top-tier venue for critical advances in biomedical research.

“We were a little surprised at the extent of clarity in our data,” Professor and Southwest National Primate Research Center Director Deepak Kaushal, Ph.D., said. “I am actually very excited to move forward trying different treatment approaches on co-infected monkeys.”

The scientific community has long assumed the reason people with HIV are more likely to develop TB is a depletion of immune cells called CD4+ T cells. However, Dr. Kaushal’s team was able to show that other effects of viral co-infection play a crucial role in this process.

Using about 40 rhesus macaques, researchers determined that lung-specific chronic immune activation is responsible for the progression of disease. Chronic immune activation is a dysfunction of immune pathways that generate molecules (cytokines and chemokines) which fight off pathogens like bacteria, viruses and fungi.

Dr. Kaushal used an analogy to explain what this dysfunction caused by HIV infection does in the body. “It’s like all the taps and faucets in your house are turned on full blast all the time,” he said. “You are going to lose a lot of water. With this dysfunction, all cytokines ad chemokines are constantly being produced to the highest levels. This dysregulates the body’s ability to fight off other infections.”

Even with the gold standard antiretroviral therapy (ART) for people with HIV, chronic immune activation still persists. Dr. Kaushal said his study shows “we need to develop approaches to target chronic immune activation,” perhaps with a drug that would be an additional therapy along with ART.

Dr. Kaushal said the implications of a new method of treatment are enormous. Up to a fourth of the world’s population is infected with tuberculosis. Most of the time, the bacterial disease remains latent (dormant). In otherwise healthy people with latent TB, only 5% will go on to develop active tuberculosis. In HIV/AIDS patients, the risk of developing active TB increases ten-fold to 50%. TB and HIV co-infection is considered a global syndemic, meaning the diseases are pandemics infecting people all around the world, and they promote each other. In parts of Sub-Saharan Africa, the rate of TB/HIV co-infection is “astronomically high,” according to Dr. Kaushal, citing statistics that show it’s 100 times higher than the rest of the world.

This discovery was 12 years in the making, starting with the creation of a nonhuman primate model for TB/HIV co-infection. Dr. Kaushal said he is hopeful new treatment strategies could reach the clinic within a decade.

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A paper published in Scientific Reports describes how researchers affiliated with the University of São Paulo’s Medical School (FM-USP) in Brazil and colleagues at institutions in Europe evaluated behaviors leading to weight gain in adolescents. Childhood obesity can favor the premature emergence of health issues such as type 2 diabetes and cardiovascular disease.

The main finding is that skipping breakfast, a common habit among teenagers, correlates directly with increased waist circumference and body mass index in this age group. The habit can lead to an unbalanced diet and other unhealthy behaviors, potentially making the adolescents vulnerable to weight gain.

“We found that skipping breakfast is associated with adiposity markers in adolescents regardless of where they live and how much sleep they get, or whether they’re male or female,” said epidemiologist Elsie Costa de Oliveira Forkert, a member of the Youth/Child Cardiovascular Risk and Environmental (YCARE) Research Group in FM-USP’s Preventive Medicine Department.

“By skipping breakfast, millions of children and adolescents around the world are probably replacing a more healthy homemade meal including dairy products, whole-grain cereal and fruit with fast food at a venue on the way to school, or at the school itself,” Forkert said.

“This typically means consuming industrialized hypercaloric foods of low nutritional value, such as deep-fried snacks, pastries, sodas and other sugary drinks, which are all directly associated with the development of obesity.”

The study was part of Forkert’s postdoctoral research, supported by São Paulo Research Foundation—FAPESP. Scientists at institutions in Austria, Belgium, Germany, Greece, Italy and Spain collaborated.

Analyzing data from two major surveys conducted in Europe and Brazil, the scientists assessed the association between energy balance-related behaviors in adolescence and markers of total and abdominal adiposity.

The European data came from the “Healthy Lifestyle in Europe by Nutrition in Adolescence” cross-sectional study (HELENA-CSS, 2006-07), which involved 3,528 adolescents in 10 major cities. The subjects were between 12.5 years and 17.5 years of age and were stratified by age, gender, region, and socioeconomic status. Males and females accounted for roughly half of the study population each (47.7 percent and 52.3 percent, respectively). The principal investigator was Luis Alberto Moreno, a professor at the University of Zaragoza’s Health Science School in Spain.

The Brazilian data came from a survey entitled “Brazilian Cardiovascular Adolescent Health” (BRACAH). Using a similar methodology, this survey was conducted in 2007 in Maringá, the third-largest city in Paraná state. It involved 991 adolescents aged 14-18 years of age. Males accounted for 45.5 percent and females accounted for 54.5 percent of the study population. The adolescents were assessed for cardiovascular risk factors and health-related behaviors.

The principal investigator for this survey was Augusto Cesar Ferreira de Moraes, a professor in the Epidemiology Department of the University of São Paulo’s Public Health School (FSP-USP).

The new study analyzed weight, height and body mass index data as indicators of overall obesity and waist circumference and waist-height ratios as indicators of abdominal obesity.

“Energy balance-related behaviors were measured by means of a questionnaire covering physical activity levels at school or at home, during leisure or while commuting, etc. Approximately 60 or more minutes per day of moderate to vigorous physical activity was considered adequate. Less than that was considered insufficient,” Forkert said.

According to Forkert, sedentary behaviors were analyzed in terms of habitual screen time (television, computer, video games), and subjects were asked to specify how many hours they usually slept on weekdays and weekends.

A separate questionnaire was applied to explore attitudes and concerns regarding food choices, preferences, healthy eating habits and lifestyle, and included a specific question about breakfast that asked subjects to agree or disagree (more or less strongly on a scale from on to seven) with the statement “I often skip breakfast.”

The scientists used the data from these surveys to investigate whether adolescents who skipped breakfast had higher adiposity markers on average than those who did not.

“Among all the energy balance-related behaviors analyzed, the strongest correlation was between skipping breakfast and the augmented average levels of obesity markers,” Forkert said.

Sedentary habits and more calories

Data from both the European and Brazilian surveys showed that male adolescents were heavier and taller on average and had larger waist circumferences than females.

“For boys who skipped breakfast, the average waist circumference was 2.61 cm larger in Europe and 2.13 cm larger in Brazil than those of boys who usually ate breakfast,” Forkert said.

“On the other hand, when we looked at how sleep time influenced the association between the other behaviors and the obesity markers, we found that the average body mass index for European and Brazilian boys who skipped breakfast was 1.29 kg/m² and 1.69 kg/m² higher, respectively, than those who ate breakfast, even when they got sufficient sleep [eight hours or more per day].”

For European and Brazilian boys, skipping breakfast was the predominant energy balance-related behavior that correlated positively with obesity indicators such as body mass index, waist circumference and waist-height ratio.

“The same was true of European girls. Skipping breakfast correlated positively with total and abdominal obesity even when sleep time was adequate,” Forkert said. “For example, the average waist circumference increased by 1.97 cm, and the waist-height ratio was 0.02 higher.”

In Brazil, girls were more sedentary than boys. In Europe, sedentary habits prevailed less among girls than among boys, but girls were also less physically active, although they were more active than Brazilian boys. The sedentary behaviors of these girls (more than two hours per day) resulted in an increased waist circumference (1.20 m on average), even when sleep time was adequate.

“However, among Brazilian boys who slept less than eight hours per day, less sleep was protective for total obesity, which fell by 0.93 kg/m² on average,” Forkert said.

“The adolescents with more sedentary habits who spent more time watching television, using a computer or playing video games probably had an unbalanced diet and consumed unhealthy food while watching television or playing,” she added, although such behaviors were not investigated in the study. “Sedentary behaviors associated with relatively high calorie consumption lead directly to obesity.”

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