This blog is the first in a series about the future of NIAID's HIV clinical research enterprise. For more information, please visit the HIV Clinical Research Enterprise page.

NIAID supports four research networks as part of its HIV clinical research enterprise. Every seven years, the Institute engages research partners, community representatives, and other public health stakeholders in a multidisciplinary evaluation of network progress toward short- and long-term scientific goals. This process takes account of knowledge gained since the networks were last funded and identifies essential course corrections based on the latest scientific and public health evidence. Subsequent NIAID HIV research investments build on the conclusions of these discussions.

Pregnancy, childbirth and the postnatal period are a key focus of NIAID HIV research and call for measures to support the health of people who could become pregnant as well as their infants. Biological changes and social dynamics such as gender inequality, intimate partner violence, and discrimination can increase the likelihood of HIV acquisition during all natal stages. Of note, breastfeeding/chestfeeding is emerging as the predominant mode of vertical HIV transmission. NIAID is committed to optimizing HIV treatment and prevention options for people who might become pregnant, people who are pregnant and lactating, newborns, and young children who are still nursing or are living with HIV. Our goals are to offer safe, effective, acceptable, and accessible tools that provide evidence-based HIV prevention choices throughout the period of reproductive potential; prevent vertical HIV transmission to infants; and enable infants born with HIV to experience long periods of HIV remission or complete HIV clearance. We think these goals can be reached with discovery and development studies to advance biomedical interventions, and implementation science to rapidly introduce state-of-the-art interventions where they are needed most urgently.

In the current evaluation of our clinical trials networks, NIAID and other stakeholders are assessing novel interventions to interrupt the unacceptably high rate of new pediatric HIV diagnoses that persist in high burden countries. Recent research is rapidly expanding the evidence base for treatment for children and pregnant people with HIV, as well as biomedical prevention tools for pregnant people and people of reproductive potential who stand to benefit from their use. Some key advances include: 

• Expanded evidence to support a cascade of multiple regulatory approvals making new therapeutic agents available to the youngest children with HIV;
• Demonstrated safety of prevention products and antiretroviral therapy (ART) throughout pregnancy, including long-acting cabotegravir for HIV pre-exposure prophylaxis (PrEP); the controlled-release vaginal ring for HIV PrEP; and integrase strand transfer inhibitor-based ART for viral suppression in people with HIV; and
• Rigorous examination of the potential of treatment initiation within hours of birth to enable ART-free HIV remission in children in a research setting.

Together, these advances open doors to improved tools for HIV prevention and treatment and help define remaining evidence gaps and research needs.

Biomedical research to accelerate evidence responsive to pediatric and perinatal needs 

As noted above, a NIAID-sponsored clinical trial led by the International Maternal Pediatric Adolescent AIDS Clinical Trials Network (IMPAACT), called IMPAACT P1115, found that four children surpassed a year of HIV remission after pausing ART. The protocol remains active with subsequent iterations of the trial in children receiving more advanced ART regimens and novel broadly neutralizing antibody-based therapy. Further research is planned to identify biomarkers to predict the likelihood of HIV remission or rebound following ART interruption. Additional studies also are needed to better understand the mechanisms by which neonatal immunity and very early ART initiation limited the formation of latent HIV reservoirs to drive the original P1115 results.

Additional research priorities include developing early infant HIV testing assays that can promptly detect vertical HIV acquisition through breastfeeding/chestfeeding; wider examination of the safety and efficacy of presumptive ART pending an HIV diagnosis; administration of very early neonatal and pediatric formulations of the latest and future generations of long-acting ARVs for prevention and treatment and antibody-based therapy; and optimization of long-acting HIV treatment regimens to support health through periods of reproductive potential, pregnancy, and lactation.    

Implementation science to strengthen delivery 

Improving HIV prevention and care through reproductive years and intense early-life HIV intervention for infants will require an unprecedented level of reproductive health, prenatal, postnatal and pediatric HIV service integration. Several key clinical and operational questions warrant investigation through implementation science. The first is assuring availability of acceptable HIV testing modalities pre-conception, as well as universal HIV testing as part of routine obstetric care, and then supporting access to a person’s preferred PrEP method or ART based on HIV status. For infants whose birthing parent has HIV, we need evidence-based models for offering very early point-of-care infant HIV diagnosis and treatment, including presumptive ART for infants exposed to HIV in utero pending confirmatory testing. We also need to understand how to better support continued engagement in care to maintain viral suppression for childbearing people with HIV through the end of the lactating period and life course. We will provide special consideration for the preferences of adolescent and young adult cisgender women who are disproportionately affected by HIV in high burden settings globally. Defining local and contextually appropriate adaptations of successful models will be paramount for successful uptake. 

The research community plays an essential role in shaping NIAID’s scientific direction and research enterprise operations. We want to hear from you. Please share your questions and comments at NextNIAIDHIVNetworks@mail.nih.gov.

About NIAID Clinical Trials Networks and Pediatric HIV

The IMPAACT Network examines prevention and treatment interventions for HIV, HIV-associated complications, and related pathogens in infants, children, and adolescents, and during pregnancy and postpartum periods. The Network is supported through grants from NIAID, with co-funding and scientific partnership from the NIH Eunice Kennedy Shriver National Institute of Child Health and Human Development and the NIH National Institute of Mental Health. Three other networks—the HIV Vaccine Trials Network, HIV Prevention Trials Network, and Advancing Clinical Therapeutics Globally for HIV/AIDS and Other Infections—generate complementary evidence and provide research infrastructure where needed when rapidly evolving prevention and treatment science has implications for IMPAACT priority populations. 

Editorial note: NIAID encourages the use of inclusive language in all communications. The terms related to lactation and pregnancy in this blog reflect the diverse gender identities and experiences of all people who stand to benefit from HIV prevention and cure research. For more information on inclusive language related to pregnancy and family, please visit the NIAID HIV Language Guide.  

‘Stepping into Science’ Highlights Variety of Scientific Careers

NIAID’s RML Campus Hosts Day-Long High School Program

Introducing local students to biomedical science and research has long been a feature of outreach programs at NIAID’s Rocky Mountain Laboratories in Hamilton, Montana.  However, realizing that traditional laboratory science – aka “bench research” – isn’t for everyone, RML staff recently invited two dozen area high school students to experience not only traditional research but also the lesser-known careers that make bench research possible.

Where bench science can be slow and methodical – scientists may spend their entire career investigating the same problem – jobs that support bench research often vary greatly from project to project. Both types of careers are rewarding and exciting – but appeal to different types of people.

“Stepping into Science,” held this spring at the RML campus, was the idea of Kamryn Cregger, who began postbaccalaureate research work at RML in August 2023. Cregger says she quickly realized that RML had amazing resources to benefit area students, and she hoped to provide them with a similar type of opportunity that she experienced as a high schooler in rural Maryland. Cregger enrolled in a biomedical leadership program that led to a pharmaceutical internship, two years of lab training, and ultimately a bachelor’s degree in plant sciences from the University of Tennessee.

Now working on tickborne disease projects at RML – and helping local middle-school students through RML’s Biomedical Research After School Scholars program – Cregger wanted to find a way to connect with college-bound high schoolers.

“With all of the scientists and staff members on site, why not show the local students what kinds of jobs there are in science in addition to bench work?” she thought. Making those types of connections also could establish the RML group as long-term mentors for students applying for college, internships, or career positions.

After a few months of planning meetings, coordinating with RML volunteers, and finding out what most appealed to students and faculty from Hamilton and Corvallis high schools – the groups arrived for the whirlwind day of activities at RML.

“Throughout the day,” Cregger said, “students asked questions about careers, RML research, medical school application processes, the differences in academic versus government research and even vaccine development!” Students received a campus tour, overview of the types of research done in the different laboratory groups and rotated through three hands-on demonstrations by virologists, animal care staff and  microscopists.

A team of RML virologists worked together to demonstrate biosafety knowledge, proper laboratory skills, such as pipetting, working in a biosafety cabinet, and dressing in personal protective equipment (PPE). They even designed a way for students to participate in a fun research-based game.

The three microscopists – Forrest Hoyt, Sophia Antonioli-Schmit and Bryan Hansen – all discussed their remarkable journeys from local high schools to RML.

In the animal care segment, “We taught them about animal husbandry, histology technicians, biologists and veterinarians,” veterinary pathologist Carl Shaia said. “Someone in each of those positions described their duties, education and how they came to RML. We also briefly touched on pay, the importance of benefits and the impact of student debt for higher education.”

RML biologist Tara Wehrly’s daughter participated in the events. Wehrly said she appreciated how the activities gave her daughter a greater understanding of the work she does.

“My daughter knows I work here, and I talk about scientific matters, but until she was on campus, it was more of an abstract concept,” Wehrly said. “I feel that Kamryn (Cregger) found the right people to give enthusiastic, informative presentations communicating the fun parts of their jobs to this group of teenagers. The discussions the kids had with post-bacs and post-docs gave them information about potential career paths that they might not have considered prior to this.”

Cregger and other event organizers already are discussing where to take the idea next, starting off with hopes of continuing the program for years to come. RML would like to inspire generations of science-loving people “and is honored to help guide the students down whatever path they choose,” according to Cregger. 

NIAID Raises Awareness to Malaria-like Diseases in W. Africa

Dengue, Zika, Chikungunya Viruses in Mali; Disease Likely Misdiagnosed

NIAID scientists and colleagues have identified dengue, Zika and chikungunya viruses in the West African country of Mali, where health care providers likely misdiagnose patients with illness from those viruses due to unavailable diagnostic tools. Because malaria is the most common fever-causing illness in rural sub-Saharan Africa, most medical workers presume patients with a fever have malaria. The primary cause of all four infectious diseases is a mosquito bite.

Records from the Malian Health Information System show that about one-third of all patient visits to health care facilities are related to malaria, with 2.37 million clinical cases.

A new study from NIAID’s Rocky Mountain Laboratories and the University of Sciences, Techniques and Technologies in Mali aims to help spread information to medical workers about the existence of the additional viral diseases. Ideally, circulating the information will help them obtain the necessary diagnostics.

The study, published in The American Journal of Tropical Medicine and Hygiene, involved 600 residents, 200 from each of the southern Malian communities of Soromba, Bamba and Banzana. The scientists detected antibodies to dengue virus in the blood of 77.2% of the residents tested; to Zika virus in 31.2%, and to chikungunya virus in 25.8%. They detected at least one of the three viruses in 84.9% of participants, meaning just 15.1% tested negative to any of the three viruses.

Evidence of the parasites that cause malaria was found in 44.5% of those tested. Unlike malaria, however, where most cases are found in children under age 14, residents over age 50 were most likely to have been exposed to dengue, Zika or chikungunya viruses. 

“Despite the high exposure risk to dengue virus in southern Mali, dengue fever cases have rarely been reported,” the researchers write. “This is likely due to the lack of diagnostic testing and the biased clinical focus on malaria in the region. Awareness of dengue virus as a cause of febrile illness needs to be urgently established in medical communities as an important public health measure.”

The scientists are hoping data from a more in-depth clinical study that just ended will provide additional details about the prevalence of these viruses in Mali. They also are planning to examine patients who have undiagnosed fevers to establish infection rates.

NIAID scientists are investigating dengue, Zika and chikungunya viruses to try and develop preventive and therapeutic treatment options, none of which exist.

Reference: S Bane, et al. Seroprevalence of Arboviruses in a Malaria Hyperendemic Area in Southern Mali. The American Journal of Tropical Medicine and Hygiene DOI: 10.4269/ajtmh.23-0803 (2024).