AIDS Archives

CRISPR gene editing identifies possible drug targets for HIV

October 19, 2022

Working with researchers at Johns Hopkins University, the Children’s National team used CRISPR gene technology to test drug targets that find and attack latent HIV, paving the way for drug treatments that may someday completely cure the virus.

Researchers at Children’s National Hospital have identified several new drug targets that may enhance the elimination of latent HIV in patients, a major bottleneck to the full treatment of the virus, according to new findings published in Science Translational Medicine.

Working with researchers at Johns Hopkins University, the Children’s National team used CRISPR gene technology to test drug targets that find and attack latent HIV, paving the way for drug treatments that may someday completely cure the virus. Currently, anti-retroviral therapies (ARTs) can only slow its progress.

Why we’re excited

“In less than one month, we were able to use CRISPR to test 20,000 gene candidates in one single experiment. It was an amazing application of the technology,” said Wei Li, Ph.D., a co-author of the study and assistant professor at the Center for Genetic Medicine Research at Children’s National. “The CRISPR technology provides a global, unbiased approach to understanding molecular aspects of HIV-1 infection, including the ways that HIV-1 enters cells and replicates. This research could someday revolutionize how we treat the virus pharmaceutically.”

The big picture

More than 30 million people worldwide live with HIV-1, the most common form of the virus that can eventually lead to AIDS. But no single agent can entirely eliminate HIV-1 in these patients.

Researchers have sought ways to attack this elusiveness and turned to the CRISPR gene-editing tool, which can locate specific bits of DNA inside a cell. They trained CRISPR screens on the HIV-1 genome to identify critical factors that allow or prevent the virus from lying latent. In the latter case, these pieces of DNA will be the ideal targets of a drug that will push the virus out of the latent stage so it can be targeted by therapies.

What’s ahead

The findings of the Children’s National and Johns Hopkins scientists point to novel drug therapies and validation systems that could someday eradicate HIV.

Bicna Song, a postdoctoral researcher in Li’s laboratory at the Center for Genetic Medicine, said that reversing HIV-1 latency will allow for the killing of infected cells and give researchers opportunities to actually cure patients with HIV.

“So far, no single latency-reversing agent – alone or in combination with another drug – has been shown to effectively reduce the latent reservoir size in persons living with HIV-1,” said Song, who contributed to the study. “With this work, we are meeting the urgent need to identify factors that can lead to new drug targets.”

Religiousness linked to improved quality of life for people with HIV

February 3, 2020

Adults living with HIV in Washington, D.C., were more likely to feel higher levels of emotional and physical well-being if they attended religious services regularly, prayed daily, felt “God’s presence,” and self-identified as religious or spiritual.

Adults living with HIV in Washington, D.C., were more likely to feel higher levels of emotional and physical well-being if they attended religious services regularly, prayed daily, felt “God’s presence,” and self-identified as religious or spiritual, according to research published online Jan. 29, 2020, in Psychology of Religion and Spirituality. By contrast, patients living with HIV who had the lowest levels of quality of life and more mental health challenges were privately religious, potentially eschewing organized religion due to fears about being stigmatized or ostracized.

“These findings are significant because they point to the untapped potential of encouraging patients living with HIV who are already religious to attend religious services regularly. Scientific evidence suggests that religions that present God as all-powerful, personal, responsive, loving, just and forgiving make a difference in health-related quality of life. By contrast, belief systems and religions that see God as punishing, angry, vengeful and distant and isolate members from their families and the larger community do not have health benefits or contribute to health-related quality of life. People who identify as spiritual also benefit from improved overall health-related quality of life,” says Maureen E. Lyon, Ph.D., FABPP, a clinical health psychologist at Children’s National Hospital, and senior study author.

“In general, patients living with HIV have reported that they wished their health care providers acknowledged their religious beliefs and spiritual struggles. Additional research is needed to gauge whether developing faith-based interventions or routine referrals to faith-based programs that welcome racial and sexual minorities improve satisfaction with treatment and health outcomes,” Lyon adds.

More than 1 million people in the U.S. live with HIV, and in 2018, 37,832 people received an HIV diagnosis in the U.S., according to the Centers for Disease Control and Prevention (CDC). In 2017, the Washington, D.C., region recorded one of nation’s highest rates of new cases of HIV: 46.3 diagnoses per 100,000 people, according to the CDC.

A research team that includes current and former Children’s National faculty wanted to learn more about the degree of religiousness and spirituality reported by people living with HIV and the interplay between religion and health-related quality of life. They recruited patients to participate in a clinical trial about family-centered advance care planning and enrolled 223 patient/family dyads in this study.

Fifty-six percent of patients were male. Eighty-six percent were African American, and their mean age was 50.8. Seventy-five percent were Christian.

The researchers identified three distinct classes of religious beliefs:

Class 1, the highest level of religiousness/spirituality, applied to people more likely to attend religious services in person each week, to pray daily, to “feel God’s presence” and to self-identify as religious and spiritual. Thirty-five percent of study participants were Class 1 and tended to be older than 40.
Class 2 applied to privately religious people who engaged in religious activities at home, like praying, and did not attend services regularly. Forty-seven percent of study participants were Class 2.
Class 3 participants self-identified as spiritual but were not involved in organized religion. Nearly 18 percent of study participants were Class 3, the lowest overall level of religiousness/spirituality.

Class 1 religiousness/spirituality was associated with increased quality of life, mental health and improved health status.

“Being committed to a welcoming religious group provides social support, a sense of identity and a way to cope with stress experienced by people living with HIV,” Lyon says. “We encourage clinicians to capitalize on patients’ spiritual beliefs that improve health – such as prayer, meditation, reading spiritual texts and attending community events – by including them in holistic treatment programs in a non-judgmental way.”

What’s more, the research team encourages clinicians to appoint a member of the team who is responsible for handling religiousness/spirituality screening and providing referrals to welcoming hospital-based chaplaincy programs or community-based religious groups.

“This is particularly challenging for HIV-positive African American men who have sex with men, as this group faces discrimination related to race and sexual orientation. Because HIV infection rates are increasing for this group, this additional outreach is all the more important,” she adds.

In addition to Lyon, study co-authors include Biostatistician Jichuan Wang, Ph.D., and Yao I. Cheng, MS., both of Children’s National; and Lead Author Katherine B. Grill, Ph.D., the former clinical coordinator for this randomized clinical trial who is currently an adjunct professor at the California Institute of Integral Studies.

Financial support for research described in this post was provided by the National Institutes of Health under award Nos. R01NR014-052-05 and UL1RR031988.

Critters bugging! Test your infectious disease knowledge

September 10, 2019

Alexandra M. Sims, M.D., FAAP, counsels grads to know their who, how and why

May 20, 2019

Alexandra M. Sims, M.D., FAAP, general academic pediatrics fellow at Children’s National, tells newly minted George Mason social sciences graduates the concrete and abstract skills they learned during their collegiate experience are exceedingly valuable.

As a 10-year-old growing up in the suburbs of Richmond, Virginia, lip syncing with friends as they pretended to be Destiny’s Child, Alexandra M. Sims, M.D., FAAP, predicted her future: She would become a doctor.

“Ten is a really funny age,” Dr. Sims told members of the 2019 graduating class from George Mason University College of Humanities and Social Sciences, the school and department from which she received her undergraduate degree in Anthropology. “I was old enough to feel compelled to contribute to the world meaningfully, but too young to know the weight of this undertaking. I was old enough to be intrigued by the science of the human body, but too young to be intimidated by the fact that there were no doctors in my family.”

Dr. Sims’ youngest sister, Bria, was born four weeks premature and died a few weeks after birth. The sting of that tragedy instilled in her a commitment to serve others and informed a lifelong passion to help society’s most marginalized.

Ten years after graduating George Mason herself, she invited this year’s newly minted graduates to distill their college experience into three terms: who, how and why:

Who means the family members and mentors who helped them enter college and persevere toward graduation.
How is their plan to change the world. The general academics pediatrics fellow at Children’s National asks kids about their unique superpower during visits to the primary care clinic at Children’s Health Center Anacostia. “I get a range of responses, and some of them are quite funny,” she told 800 social sciences graduates gathered for their degree celebration. “Some really surprise me in other ways. ‘I want to be kind.’ ‘I want to help people.’ ‘I want to take care of my parents.’ ”
Why is the reason they continue to do what they’re doing. For Dr. Sims, that’s service and mitigating health disparities, a mission that has led her to travel around the globe conducting HIV/AIDS outreach and building coalitions near and far. Her current work is domestic, as she seeks advocates for at-risk communities through health services research.

“So, come back to these when you’re feeling unsure or uneasy: your WHO, your HOW and your WHY. Know that your time here at Mason is time well spent, and that the skills that you’ve gained, both the concrete and the abstract, are exceedingly valuable,” she advised the group.

Community-based AIDS prevention organization recognizes Children’s National Health System

April 8, 2019

Credit: Don Bon Photography

The Division of Adolescent and Young Adult Medicine at Children’s National Health System was honored with the Thurlow Evans Tibbs, Jr. Award for outstanding service in HIV prevention by Us Helping Us, People Into Living, a community-based AIDS service organization committed to reducing HIV infection in the African American community on April 2, 2019 in Washington, D.C.

“We are so honored to receive the Thurlow Evans Tibbs, Jr. Award from our colleagues and friends, Us Helping Us, People Into Living,” said Dr. Lawrence D’Angelo, director of the Youth Pride Clinic and Burgess Clinics, a division of Adolescent and Young Adult Medicine at Children’s National. “We have always considered Us Helping Us as an essential partner in this struggle and so it’s ingrained as a part of the community. It has been our honor to work with them, and an equal honor to be recognized in this way by them. We are so grateful and so proud!”

Dr. Lawrence D’Angelo and his team at the Burgess Clinic have cared for over 750 HIV infected youth, many who have gone on to live long and productive lives since the clinic opened its doors in 1988. The clinic started the Washington Area Consortium on HIV infection in Youth (WACHIVY) which later became MetroTeenAIDS Metro TeenAIDS, one of the largest and most successful prevention education programs for youth in the country. The Burgess Clinic is the home of over a dozen NIH and foundation grants that supported the diagnosis and treatment of HIV infected youth, accounting for over $55M in support.

“Receiving the Thurlow Evans Tibbs, Jr. Award from Us Helping Us, People Into Living is an honor beyond anything we could have hoped for,” says Dr. D’Angelo. “Our programs were started at the same time to meet similar needs and for years we have worked together and appreciated each other’s efforts in serving our community. D.C. could not have attained the progress it has made in the struggle against HIV without Us Helping Us, People Into Living and knowing that makes this award all the more special.”

Us Helping Us, People Into Living was incorporated in 1988 as a support group for HIV-positive black gay men.

A growing list of factors that impact CKD severity for kids

November 20, 2018

Myriad biological and societal factors can impact the occurrence and accelerate progression of chronic kidney disease for children of African descent – including preterm birth, exposure to toxins during gestation and lower socioeconomic status – and can complicate these children’s access to effective treatments.

Myriad biological and societal factors can impact the occurrence and accelerate progression of chronic kidney disease (CKD) for children of African descent – including preterm birth, exposure to toxins during gestation and lower socioeconomic status – and can complicate these children’s access to effective treatments, according to an invited commentary published in the November 2018 edition of American Journal of Kidney Diseases.

Clinicians caring for “these vulnerable children should be mindful of these multiple competing and compounding issues as treatment options are being considered along the continuum from CKD to kidney failure to transplantation,” writes Marva Moxey-Mims, M.D., chief of the Division of Nephrology at Children’s National Health System.

The supplemental article was informed by lessons learned from The Chronic Kidney Disease in Children (CKiD) longitudinal study and conversations that occurred during the Frank M. Norfleet Forum for Advancement of Health, “African Americans and Kidney Disease in the 21^st Century.”

African American children represent 23 percent of the overall population of kids with CKD in the CKiD study. While acquired kidney diseases can get their start during childhood when the diseases betray few symptoms, the full impact of illness may not be felt until adulthood. A number of factors can uniquely affect children of African descent, heightening risk for some kids who already are predisposed to suffering more severe symptoms. These include:

Preterm birth. African American children make up 36 percent of patients in CKiD with glomerular disease, which tends to have faster progression to end-stage renal disease. These diseases impair kidney function by weakening glomeruli, which impairs the kidneys’ ability to clean blood. Patients with a high-risk apolipoprotein L1 (APOL1) genotype already are at higher risk for focal segmental glomerulosclerosis (FSGS) and CKD. Researchers hypothesize that preterm birth may represent “a second hit that facilitates the development of glomerular damage resulting from the high-risk genotype.” According to the Centers for Disease Control and Prevention, 1 in 10 U.S. infants in 2016 was born preterm, e.g., prior to 37 weeks gestation.
APOL1 genotype. Compared with children who had a low-risk genotype and FSGS, children with a high-risk genotype had higher rates of uncontrolled hypertension, left ventricular hypertrophy, elevated C-reactive protein levels and obesity.
Human immunodeficiency viral (HIV) status. About 65 percent of U.S. children with HIV-1/AIDS are African American. In a recent nested case-control study of children infected with HIV in the womb, infants with high-risk APOL1 genotypes were 3.5 times more likely to develop CKD with viral infection serving as “a likely second hit.”
Access to kidney transplant. African American adults experience a faster transition to end-stage renal disease and are less likely to receive kidney transplants. African American children with CKD from nonglomerular diseases begin renal replacement therapy 1.6 years earlier than children of other races, after adjusting for socioeconomic status. Their wait for dialysis therapy was 37.5 percent shorter. However, these African American children waited 53.7 percent longer for transplants. Although donor blood types, genetic characteristics and other biological factors each play contributing roles, “these findings may reflect sociocultural and institutional differences not captured by socioeconomic status,” Dr. Moxey-Mims writes.

To alleviate future health care disparities, she suggests that additional research explore the impact of expanding services to pregnant women to lower their chances of giving birth prematurely; early childhood interventions to help boost children’s educational outcomes, future job prospects and income levels; expanded studies about the impact of environmental toxicities on prenatal and postnatal development; and heightened surveillance of preterm infants as they grow older to spot signs of kidney disease earlier to slow or prevent disease progression.

“Clinicians can now begin to take into account genetics, socioeconomic status and the impact of the built environment, rather than blaming people and assuming that their behavior alone brought on kidney disease,” Dr. Moxey-Mims adds. “Smoking, not eating properly and not exercising can certainly make people vulnerable to disease. However, there are so many factors that go into developing a disease that patients cannot control: You don’t control to whom you’re born, where you live or available resources where you live. These research projects will be useful to help us really get to the bottom of which factors we can impact and which things can’t we prevent but can strive to mitigate.”

The article covered in this post is part of a supplement that arose from the Frank M. Norfleet Forum for Advancement of Health: African Americans and Kidney Disease in the 21st Century, held March 24, 2017, in Memphis, Tennessee. The Forum and the publication of this supplement were funded by the Frank M. Norfleet Forum for Advancement of Health, the Community Foundation of Greater Memphis and the University of Tennessee Health Science Center.

Natella Yurievna Rakhmanina named to regional HIV planning commission

September 13, 2018

Natella Rakhamania

Natella Yurievna Rakhmanina, M.D., Ph.D., FAAP, AAHIVS, director of Ryan White HIV Services at Children’s National Health System, was appointed a commissioner to the Washington, D.C., Regional Planning Commission on Health and HIV.

Dr. Rakhmanina will be among the District of Columbia board and commission appointees honored during a swearing-in ceremony on Sept. 17, 2018, at the Walter Washington Convention Center.

Looking back over the last decade, she says the District has made impressive progress in lowering the prevalence rate of human immunodeficiency virus (HIV), which in 2002 had 1,686 per 100,000 District residents diagnosed with AIDS.

“It was really high. I was stunned coming to clinic and seeing a large number of kids and adolescents in care and many suffering significant complications, as our treatment options were limited at the time,” she says.

Since that time, DC Health has made “incredible investments” and adopted innovative approaches, such as name-based reporting of HIV and a Red Carpet program, to ensure newly diagnosed people are quickly linked with care. As a proud partner of DC Health’s HIV/AIDS, Hepatitis, STD and TB Administration, Children’s National launched a campaign in 2009 to universally test adolescents for HIV in two pediatric emergency departments (ED), she says.

“All teenagers aged 13 and older who arrive for any medical diagnosis are offered an oral HIV test. Children’s National ED-based HIV screening program alone has tested 30,000 children at both of our emergency departments,” she says. “We’re still not at our goal. However, the prevalence of HIV had dropped to 1.9 percent in the latest department of health analysis. We are doing better. We have much fewer people dying from AIDS. We are diagnosing earlier.”

What’s more, trends in mother-to-child transmission, a major route of transmission for pediatric HIV, also have improved in D.C.

“In 2006, our maternal HIV transmission rates were among the highest in the nation. But, in 2013, 2014 and 2015 there were zero cases. We have seen some setbacks recently, however. In 2016, there were three perinatally acquired cases and four in 2017, but these cases came out of the larger Metropolitan D.C. area,” she explains. “Every perinatally transmitted case for us is a red star. We work very closely with the regional departments of health. We really want to get back to zero cases of maternal transmission in the region.”

The regional planning commission meets several times per year to decide how to distribute federal funding in Washington and the Metropolitan D.C. area to support HIV prevention, diagnosis, treatment and care.

“My voice on the council is to make sure I speak up for services for mothers, children and adolescents,” Dr. Rakhmanina says. “The biggest challenge of HIV care remains treating children. There’s a good selection of medicines for adults, but not all are suited for kids. Young children in particular can’t be given one pill once a day. Really young children can’t swallow a pill. Using a liquid formulation, which kids prefer, may mean opening three different bottles twice daily and swallowing a liquid that often doesn’t taste good.”

Adolescents diagnosed with HIV also find medication adherence challenging, she says.

“At that age, they face a lot of challenges to self-acceptance and disease management, in part, because it’s not a physical disability. A young person with HIV may not feel anything,” she says. “They struggle with staying on daily medications. Many of them tell us they don’t want to think about HIV and face stigma.”

Another ongoing challenge is ensuring moms living with HIV remain on medicines after they’ve given birth.

“They’re tremendously committed to continuing treatment while pregnant: Treatment means their babies are born free of HIV,” she says. “That is a great success. Once the baby is born, many times the women bring their babies to be tested, but the woman’s own health becomes less of a priority. We see a drop in adherence once they have the baby.”

By serving on the commission, Dr. Rakhmanina aims to push to extend Children’s commitment to excellence beyond its walls.

Being a young parent while also HIV positive

March 20, 2018

“We realize that at some point in time, these patients will have to transition their care to an adult setting, and they will confront a different kind of health system,” says Lawrence D’Angelo, M.D., M.P.H. “We want to make sure all of their providers will be able to help them advocate for themselves and for their children.”

By the time the human immunodeficiency virus (HIV) – the virus that causes AIDS – first came to the public consciousness in the 1980s, it was clear that infected pregnant mothers readily pass it to their babies. For those infected babies to eventually have their own children was inconceivable then, says Lawrence J. D’Angelo, M.D., M.P.H., adolescent medicine specialist at Children’s National Health System. Before the advent of antiretroviral therapy, AIDS was universally fatal.

Now, about 22 percent of young adults with HIV have lived with this disease their entire lives. And like many people this age, they’re exploring romantic relationships, sex and – for some – parenthood. This unexpected turn of events, Dr. D’Angelo explains, has left many health care providers unprepared.

“We never expected that these individuals would live to reach early adulthood, so we certainly didn’t expect them to be involved in parenting,” he says. “We have no real knowledge of what to expect from them or how best to support them because we don’t understand what they’re going through.”

To learn more about these young parents living with perinatally acquired HIV (PHIV), Dr. D’Angelo worked with Cynthia Fair, professor of human services studies and public health studies coordinator at Elon University. The two conducted a qualitative assessment of parents with PHIV. After recruiting 17 individuals who fit this description directly from Dr. D’Angelo’s practice, interviewers on the research team sat down with study participants to have a conversation about what it was like to parent while also being HIV positive. They asked standard questions, such as: What do you think makes a good parent? And, describe your relationship with your parents or caregivers. How does this relate, if at all, to your views on parenthood?

The team then transcribed these interviews and fed the text into a qualitative analysis program. With the aid of this software, and their own manual analysis, the researchers found several themes emerge from the conversations.

About 90 percent of the interviews focused on challenges universal to nearly every parent: Worries about a baby taking a bottle or sleeping through the night, struggles with discipline, concerns about money. “For the most part, these are young parents with a chronic illness just trying to be good parents,” says Fair, lead author of the study published Nov. 1, 2017 in AIDS Patient Care and STDs.

However, she adds, HIV inserts an added layer of complexity. Many of the parents said they felt deprived of the opportunity to enjoy lives as long and healthy as their peers. Consequently, having a child carried a sense of pressure to accomplish more in life for their children and to leave a positive legacy. Some worried that their own HIV status would stigmatize their children and that people outside their families would automatically assume their children were HIV positive when they weren’t.

All but one parent in the study had a child who was HIV negative, but even those children require regular testing to make sure they maintain that status. Parents with infants prescribed preventive protocols spoke about the exhaustion of having to deliver prophylactic medicines around the clock. The sole parent in the study with an HIV-positive child was separated from the baby’s father; she talked about the stress of not knowing whether her baby was receiving the necessary medicines to stay healthy when the child wasn’t with her.

These young parents also spoke with interviewers about the role their own pediatric care providers played in helping them make the transition to parenthood. For example, social workers on one study participant’s care team stepped in when she had nowhere to live, finding her an appropriate shelter. Another talked about how her desire to be a good parent was strongly influenced by the care she was given by her medical providers growing up. Many of the study participants had lost one or both parents to HIV or had absentee parents due to incarceration or other causes, says Fair, making their relationships with their medical team one of the few constants they could count on.

That’s why helping care providers develop a deep understanding of the perspectives of PHIV parents is even more important, particularly as these individuals move from pediatric to adult care settings, says Dr. D’Angelo, the study’s senior author and director of the Youth Pride and Burgess Clinics at Children’s National.

“We realize that at some point in time, these patients will have to transition their care to an adult setting, and they will confront a different kind of health system,” he says. “We want to make sure all of their providers will be able to help them advocate for themselves and for their children.”

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Why we’re excited

The big picture

What’s ahead