Discovery, Development and Delivery for an Increasingly Interconnected HIV Landscape 

By Carl Dieffenbach, Ph.D., director, Division of AIDS, NIAID

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

The NIAID HIV clinical research enterprise has celebrated important scientific advances since awards were made to the current networks in 2020. These achievements include the culminating steps in decades of research that led to approval of the first generation of long-acting medications for HIV prevention—a milestone that raises the standard for any future antiretroviral drug development to levels unimaginable even a decade ago. Our research has highlighted opportunities to maintain the overall health of people with HIV throughout their lifespans. We continue to expand the boundaries of scientific innovation in pursuit of durable technologies that could hasten an end to the HIV pandemic, especially preventive vaccines and curative therapy. During the COVID-19 public health emergency, our networks stepped forward to deliver swift results that advanced vaccines and therapeutics within a year of the World Health Organization declaring the global pandemic, while maintaining progress on our HIV research agenda. The impact of this collective scientific progress is evident worldwide.

Together with my NIH colleagues, I express sincere gratitude to the leaders and staff of current clinical trials networks, our research and civil society partners, and most importantly, clinical study participants and their loved ones, for their enduring commitment to supporting science that changes lives.

As we do every seven years, we are at a point in the funding cycle when our 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 and priorities. Subsequent NIAID HIV research investments will build on the conclusions of these discussions.

Looking to the future, we envision an HIV research enterprise that follows a logical evolution in addressing new scientific priorities informed by previous research progress. We will fund our next networks to align with updated research goals to take us through the end of 2034. The HIV research community’s outstanding infrastructure is the model for biomedical research. Now, our capacity must reflect an increasing interdependence across clinical practice areas and public health contexts. Our goals for the next networks are to:

• Maintain our support for core discovery and translational research to address gaps in biomedical HIV prevention and treatment, including a vaccine and therapeutic remission or cure. Our objective is to identify effective interventions that expand user choice and access, as well as improve quality of life across the lifespan;
• Provide the multidisciplinary leadership required to address the intersections between HIV and other diseases and conditions throughout the lifespan, including noncommunicable diseases, such as diabetes mellitus and substance use disorder, and infectious diseases that share health determinants with HIV, such tuberculosis and hepatitis;
• Compress protocol development and approval timelines for small and early-stage trials to enable more timely translation of research concepts to active studies; 
• Respond to discrete implementation science research questions as defined by our implementation counterparts, including federal partners at the Centers for Disease Control and Prevention, Health Resources and Services Administration, U.S. Agency for International Development, agencies implementing the U.S. President’s Emergency Plan for AIDS Relief, and other nongovernmental funders and implementing organizations worldwide;  
• Draw from nimble and effective partnerships at all levels to leverage the necessary combination of financial resources, scientific expertise, and community leadership and operational capacity to perform clinical research that is accessible to and representative of the populations most affected by HIV, especially people and communities that have been underserved in the HIV response; 
• Leverage our partners’ platforms if called on to close critical evidence gaps for pandemic response; and,
• Plan for impact by mapping clear pathways to rapid regulatory decisions, scalable production, and fair pricing before the start of any efficacy study.

Our shared goal is to produce tools and evidence to facilitate meaningful reductions in HIV incidence, morbidity and mortality globally. I invite you to continue sharing your thoughts with us to help shape the future of HIV clinical research, and to review the blogs on specialized topics that we will continue to post on the HIV Clinical Research Enterprise page in the coming weeks. Please share your feedback, comments, and questions at NextNIAIDHIVNetworks@mail.nih.gov. Submissions will be accepted through December 2024. 

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.  

by Jeanne Marrazzo, M.D., M.P.H., NIAID Director

The HIV research community is led by scientists with deep personal commitments to improving the lives of people with and affected by HIV. Some researchers, like me, have pursued this cause since the start of the HIV pandemic, growing our careers studying HIV from basic to implementation science. Our collective decades of work have generated HIV testing, prevention and treatment options beyond what we could have imagined in the 1980s. Those advances enable NIAID to explore new frontiers: expanding HIV prevention and treatment modalities, increasing understanding of the interplay between HIV and other infectious and non-communicable diseases, optimizing choice and convenience, and building on the ever-growing knowledge base that we need to develop a preventive vaccine and cure. The next generation of leaders will bring these concepts to fruition, and we need to welcome and support them into the complex and competitive field of HIV science.

Click below for a video in which NIAID grantees and I discuss the value and experience of early-stage HIV investigators (the audio described version is here):

NIAID wants to fund more new HIV scientists and we have special programs and funding approaches to meet that goal. This week, the NIH Office of AIDS Research will host a virtual workshop on early-career HIV investigators tomorrow, April 24, and NIAID will host its next grant writing Webinars in May, June, and July.

For more information about programs and support for new and early-stage investigators as well as people starting to implement their first independent grant, visit these NIAID and NIH resources: 

Information for New Investigators (NIAID)

HIV/AIDS Information for Researchers (NIAID)

OAR Early Career Investigator Resources (NIH)

Resources of Interest to Early-Stage Investigators (NIH)

Early Career Reviewer Program (NIH)

Viral hepatitis is an inflammatory liver disease caused by infection with any of the known hepatitis viruses—A, B, C, D, and E. Most of the global viral hepatitis burden is from hepatitis B and C, which affect 354 million people and result in 1.1 million deaths annually. The Centers for Disease Control and Prevention estimates that in 2020 there were 14,000 and 50,300 new acute infections of hepatitis B and C in the United States, respectively, while at least 880,000 people in the country were living with chronic (long-term) hepatitis B and 2.4 million people had chronic hepatitis C. About half of those with viral hepatitis are unaware of their infection. Chronic and persistent inflammation from the disease can lead to liver failure, cirrhosis, or liver cancer. Viral hepatitis affects all ages and there are pronounced inequities in disease outcomes in the United States. Hepatitis B and C disproportionately affect people living with HIV, and HIV increases the rate of complications and death in people with viral hepatitis.

On this World Hepatitis Day, the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health, shares a snapshot of its investments in basic (laboratory), preclinical (laboratory/animal), and clinical (human) research to improve screening, prevention and treatment for hepatitis B and C. Scientists in the Hepatic Pathogenesis and Structural Virology sections of NIAID’s Laboratory of Infectious Diseases conduct basic and translational research to better understand hepatitis B and C disease progression, clarify the role of hepatitis viruses in liver cancer, and inform discovery of new vaccines, medicine and technologies. Both NIAID’s Division of AIDS (DAIDS) and the Division of Microbiology and Infectious Disease (DMID) support scientific programs focused on hepatitis B and C research and curative strategies, reflecting the widespread impact of viral hepatitis and the urgent need for safe and effective interventions.

Finding a hepatitis B cure

Hepatitis B continues to cause disease and death even though a highly effective preventive vaccine has been available for decades. Some people with acute hepatitis B can naturally clear the infection. In others, chronic HBV requires lifelong treatment to suppress the virus. More research is need to identify novel therapeutic options and strategies to minimize the treatment burden and, ideally, identify a cure for hepatitis B. NIAID is supporting research on a variety of basic, translational and therapeutic science concepts designed to cure hepatitis B, including in people with HIV. DMID recently announced an initiative to develop new antiviral drugs that can eliminate hepatitis B genetic material from infected cells, and DAIDS is complementing that work with clinical studies of therapeutic agents and vaccines that will include evaluation of their safety and efficacy in people living with HIV.

Streamlining the hepatitis C response

In 2011, direct-acting antivirals (DAA) revolutionized hepatitis C therapy and have since been observed to cure 95% of cases. Despite DAA availability for more than a decade, only one in three people in the United States diagnosed with hepatitis C receive curative treatment. These circumstances underscore the importance of increasing access to and convenience of diagnosis and treatment, as well as the need for a preventive vaccine. Developing a hepatitis C vaccine is challenging because of the genetic diversity of hepatitis C circulating in the population, necessitating broadly reactive vaccine technology. DMID awarded multiple grants to advance new hepatitis C vaccine designs in 2021. To better enable people to know their hepatitis C status, NIAID and other NIH institutes are supporting discovery of improved point-of-care hepatitis C testing that could be used in community and healthcare settings alike, and eliminate the need to wait for laboratory-based diagnostics. They are also supporting development of self-testing technology that people can use to screen themselves. DAIDS will soon launch an initiative to develop long-acting DAAs that could reduce the number of doses required for a full course of therapy. A recent NIAID-supported study showed even with an existing 84-tablet DAA regimen, most people with hepatitis C experienced favorable treatment outcomes without in-person healthcare visits for the duration of treatment. These innovations in diagnostics and treatment strategies aim to enable a “single-encounter cure” wherein a person could learn their hepatitis C status and collect their treatment in one healthcare visit.

These research priorities are among the current efforts in NIAID’s 60-year pursuit of scientific advances to improve the health outcomes of people with viral hepatitis. For more information on US government research to help eliminate viral hepatitis, please visit:

• NIAID Diseases & Conditions: Hepatitis
• Trans-NIH Strategic Plan to Cure Hepatitis B
• Health and Human Services Viral Hepatitis National Strategic Plan