The Ebola outbreaks in 2014 and 2016 resulted in high mortality; however, many people who were infected recovered. Studies have demonstrated that after recovery Ebola virus can persist throughout the body in the eyes, brain, semen, human milk, and vaginal secretions. One study found that viral RNA could be detected in human milk over a year after recovery. Given this, understanding the persistence of Ebola virus post infection is a critical women’s health issue, particularly in individuals of child-bearing potential. This study assessed viral persistence or reactivation in pregnancy, pregnancy outcomes, and infant growth and development.

An observational cohort study was conducted in a subgroup of individuals who were enrolled in the PREVAIL III (Partnership for Research on Ebola Virus in Liberia) longitudinal survival study that was launched in 2015. Participants self-reported pregnancies and two groups were compared: seropositive individuals who had recovered from Ebola virus disease and seronegative individuals who had close contact with people infected with Ebola. Of the 1,566 participants enrolled between 2015 and 2017, 639 became pregnant (215 seropositive, 424 seronegative), and 589 reported their pregnancy outcomes. Rates of livebirths and other pregnancy measures were assessed in both study groups, and PCR testing was conducted in samples of placenta, parental   and cord blood, human milk, and vaginal secretions from those in the seropositive group. The children born in the seropositive group were assessed every 6 months for 2 years on markers of growth and neurodevelopment.

The results of the study demonstrated low risk of Ebola virus reactivation peripartum and postpartum and low risk of adverse birth outcomes. Ebola survivors can have safe and successful pregnancies, especially when conception occurs over a year after recovery from acute infection. Because reactivation during the peripartum period was unlikely, seropositive individuals were therefore unlikely to transmit Ebola virus to their infants, contacts, or caregivers. Neonates of those who have recovered from Ebola virus disease had high concentrations of transplacental Ebola antibodies, suggesting robust immune response and early protection from Ebola virus. These findings indicate that healthcare and support can be offered without infection risk to providers.

References:

Fallah, MP et al. Pregnancy, pregnancy outcomes, and infant growth and development after recovery from Ebola virus disease in Liberia: an observational cohort study. Lancet Glob Health. DOI 10.1016/S2214-109X(23)00210-3

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)

Sexually transmitted infections (STIs) are caused by bacteria, viruses, or parasites. STIs have a devastating impact on adults and infants and annually affect millions of people in the United States. Certain STIs can increase a person’s risk of developing cancer and increase the likelihood of acquiring or transmitting HIV. In addition, STIs can cause long-term health complications, especially in the reproductive and central nervous systems. In rare cases, they can lead to serious illness or death. 

NIAID supports research across the spectrum from basic to clinical science to develop effective diagnostic, preventive and therapeutic approaches to STIs in alignment with the National STI Strategic Plan. In recognition of National STI Awareness Week, NIAID shares a snapshot of new projects and recent scientific advances in STI research. 

Improving treatment for syphilis and trichomoniasis

New reports of syphilis and congenital syphilis are increasing at an alarming rate in the United States. Syphilis is caused by the bacterium Treponema pallidum. Benzathine penicillin G (BPG) is one of only a few antibiotics known to effectively treat syphilis. There is currently a shortage of BPG, and some people are allergic to penicillin antibiotics. In February 2024, NIAID convened a workshop with a wide range of experts on alternative therapies to BPG for the treatment of adult syphilis, neurosyphilis, and syphilis in pregnant persons and infants. The workshop addressed preclinical evaluation of candidate drugs, the potential need for studies on how candidate drugs are processed in the body during pregnancy, and how to approach clinical trials of treatment for congenital syphilis. This work is part of NIAID’s comprehensive portfolio of syphilis diagnosis, prevention, and treatment research. 

Trichomoniasis is the most common parasitic STI, caused by Trichomonas vaginalis. Trichomoniasis can increase the risk of getting or spreading other STIs, including HIV. The parasite can also cause inflammation of the cervix and the urethra. T. vaginalis is treated with an antibiotic drug class called nitroimidazoles. The currently recommended nitroimidazole, called metronidazole, cures 84-98% of T. vaginalis cases but does have high rates of breakthrough infection. A new project led by Tulane University will examine a single dose of secnidazole, a medicine in the same drug class, as a more effective and cost-effective treatment option for women and men. 

Developing a vaccine for herpes simplex virus 2

Herpes simplex virus 2 (HSV-2) is a common subtype of herpes simplex virus that is transmitted through sexual contact. The Centers for Disease Control and Prevention estimates that 18.6 million people aged 15 years and older United States live with HSV-2. In severe cases, HSV-2 may lead to life-threatening or long-term complications. There is no licensed preventive HSV-2 vaccine, and there is no cure. A new project led by the University of Pennsylvania seeks to define correlates of protection for HSV-2, meaning they intend to identify immune processes involved in preventing HSV-2 disease. They will do this by analyzing laboratory samples from animal studies of a promising preventive vaccine candidate that they developed with prior funding. That vaccine candidate is also now in an industry-sponsored early-stage clinical trial. The same project will expand on the HSV-2 targets in the preventive vaccine to develop a therapeutic vaccine concept to reduce recurrent outbreaks. This research responds to the scientific priorities in the NIH Strategic Plan for Herpes Simplex Virus Research.

Increasing fundamental knowledge of bacterial vaginosis 

Bacterial vaginosis (BV) results from an imbalance in the vaginal microbiome. BV can be caused by sexual activity, douches and menstrual products. BV can increase women’s biological susceptibility to HIV and other STIs and can cause premature birth or low birthweight if untreated in pregnant people. In a recent publication, NIAID-supported researchers, led by researchers at the University of Washington and University of California San Diego, shared findings on how damage to the vaginal skin barrier occurs during bacterial vaginosis. Those skin barrier cells, called epithelial cells, are covered in carbohydrate molecules called glycans. The research team found that people with BV had damaged glycans on their vaginal epithelial cells. They suggested that future work should examine the relationship between treatment and restoration of normal glycans. If an association is detected, it could help healthcare providers monitor for successful treatment outcomes to reduce the likelihood that BV will return after a course of treatment. The findings were published in Science Translational Medicine. 

These activities are among the research investments in NIAID’s STI portfolio. For more information on STIs, please visit:

• NIAID Diseases & Conditions: Sexually Transmitted Infections
• U.S. Department of Health and Human Services STI National Strategic Plan

The National Institutes of Health recently issued $26M in awards to HIV research institutions in its fifth year supporting implementation science under the Ending the HIV Epidemic in the U.S. (EHE) initiative. These awards are the latest investments in a program that is rapidly and rigorously generating evidence to inform the unified domestic HIV response by agencies in the Department of Health and Human Services. 

The EHE initiative aims to achieve a 90% reduction in the number of new HIV infections in the United States by 2030. Since the initiative was announced in 2019, NIH has contributed by supporting implementation science projects through its network of Centers for AIDS Research (CFAR) and the National Institute of Mental Health (NIMH) AIDS Research Centers (ARC). CFARs are co-funded by 11 NIH institutes and centers (ICs), including the National Institute of Allergy and Infectious Diseases (NIAID). NIH ICs provide scientific stewardship to participating institutions in collaboration with the Fogarty International Center and the NIH Office of AIDS Research, which coordinates the NIH HIV research program across the agency. CFAR and ARC-affiliated investigators conduct research in jurisdictions that are disproportionately affected by HIV, and many of the CFAR and ARC member institutions are based in these communities. 

VIDEO: Jeanne Marrazzo, M.D., M.P.H., NIAID Director, discusses NIH’s role in the EHE (audio description version here):

NIH EHE projects enable academic institutions to partner with state and local leaders to jointly translate implementation research findings into improved delivery of HIV testing, prevention, treatment, and response services for priority populations and in priority geographic areas. Projects funded this year are designed to increase and share available knowledge on locally appropriate strategies to: 

• detect and respond to HIV “clusters,” i.e., groups of people and communities experiencing rapid HIV transmission;
• leverage pharmacies as HIV service locations; 
• ensure uninterrupted HIV care for people returning to their communities following incarceration; and
• develop approaches that address intersecting diseases and conditions that exacerbate health inequities and impact HIV outcomes, including such as viral hepatitis, sexually transmitted infections, and substance use and mental health disorders.

Since Fiscal Year 2019, NIH has funded 253 projects across 50 geographic areas prioritized by EHE. The latest EHE awards to CFARs and ARCs support 47 projects, 8 implementation science hubs, and 1 coordinating center. Hubs provide technical support, coaching, training, and consultative services to funded EHE research teams. The coordinating center provides infrastructure for collaboration and sharing best practices in HIV implementation science. In addition to the CFAR/ARC supplements, NIH supported multiple larger research projects in 2023, including 3 R01 awards, 2 R34 awards, and 1 coordinating center. In September 2023, NIH released a Notice of Special Interest to solicit project proposals from independent investigators for Fiscal Year 2024.

EHE Project Spotlights

The knowledge generated by NIH EHE projects is reviewed with HHS EHE partners to accelerate learning and program improvement. Two projects below illustrate how EHE implementation science projects have already enhanced locally tailored HIV service delivery:

Miami, Florida

Miami-Dade County, Florida has one of the highest rates of HIV incidence in the United States, and yet use of pre-exposure prophylaxis (PrEP) to prevent HIV acquisition remains relatively low. Researchers at the University of Miami, in collaboration with the Florida Department of Health (DOH) and a local community-based organization called Prevention305, developed a process to apply real-time DOH epidemiologic data to prioritize new geographic locations for placement of their mobile PrEP clinics. In collaboration with community partners, the project developed a new outreach approach: “Test-to-PrEP,” in which people using PrEP are engaged to distribute free HIV self-tests and PrEP referrals through their social networks. They have worked with 100 current PrEP clients to engage members of their social network with information about PrEP provide them with HIV self-tests. More than one third of the 117 HIV self-test kit recipients who confirmed they used the test reported they had not previously known about PrEP. Self-reported knowledge and likelihood to use PrEP increased significantly after kit receipt. PrEP clients also reported feeling comfortable with the distribution and enthusiastic about the strategy. Their work has provided a blueprint for mobile HIV prevention and related services as a strategy to interrupt further transmission.

Mobile clinic service team in the Liberty City neighborhood of Miami, Florida

Credit: University of Miami

Shelby County, Tennessee

Rural areas like Shelby County pose distinct challenges to HIV service delivery, including a lack of outpatient providers and fragmented health care and social services, as well as stigma and medical mistrust. To overcome these barriers, researchers from University of Massachusetts, Lowell, in collaboration with the University of Memphis and the Shelby County Health Department, used an implementation research approach to adapt and provide an evidence-based training and capacity-building program in HIV care for existing community health workers (CHWs), with input from HIV care providers, people with HIV, and CHWs. CHWs are frontline public health workers who are also members of the community they serve. The team has trained 67 CHW to support HIV care across eight agencies and has provided coaching sessions to supervisors around how to sustain this workforce. They are assessing the sustainability and effectiveness of this program in addressing service gaps and improving health outcomes through follow-up surveys with health care agency staff and county health leaders. 

Community health worker Michelle Anderson discussing culturally relevant care HIV care with colleagues in Memphis, Tennessee.

Credit: University of Massachusetts, Lowell

In addition to NIH, HHS agencies and offices participating in EHE include the Centers for Disease Control and Prevention; the Health Resources and Services Administration; the Indian Health Service; the Office of the Assistant Secretary for Health; and the Substance Abuse and Mental Health Services Administration. 

To view a complete list of NIH research projects supported with EHE initiative funding, please visit the awards page. 

To learn more about EHE, please visit HIV.gov.

Reference: 

Butts, SA et al. Addressing disparities in Pre-exposure Prophylaxis (PrEP) access: implementing a community-centered mobile PrEP program in South Florida. BMC Health Services Research. DOI 10.1186/s12913-023-10277-1 (2023).

Johnson, AL et al. “Test-To-PrEP”: Assessing Reach and Adoption of a New Approach to Increase HIV Testing and PrEP Knowledge Using HIV Self-Test Kit Distribution Through PrEP Clients' Social Networks. Journal of Acquired Immune Deficiency Syndromes. DOI 10.1097/QAI.0000000000003294 (2023). 

Rajabiun, S et al. Using Implementation Science to Promote Integration and Sustainability of Community Health Workers in the HIV Workforce. Journal of Acquired Immune Deficiency Syndromes. DOI 10.1097/QAI.0000000000002966 (2023).

Switching to an antiretroviral therapy (ART) regimen containing the drug dolutegravir was associated with a significant temporary increase in reservoirs of latent HIV, according to a new analysis from a study in Uganda. HIV reservoirs are cells where HIV lies dormant and cannot be reached by the immune system or ART. They are central to HIV’s persistence, preventing current treatments from clearing the virus from the body. The findings were published today in eBioMedicine.

When taken as prescribed, ART can stop HIV from replicating. The different classes of available antiretroviral drugs (ARVs) interrupt different stages of HIV replication. People are often prescribed drug regimens composed of multiple drug classes to increase the likelihood that ART will fully suppress HIV replication. In 2018, many countries began using dolutegravir-based ART regimens following studies that showed the drug had higher efficacy and fewer side effects than the drugs that had been in use previously. Uganda was among these countries and recommended dolutegravir together with the ARVs tenofovir and lamivudine for all people whose HIV was treatable with those drugs.

In 2015, NIH scientists and researchers from the Rakai Health Sciences Program in Uganda began a longitudinal study of reservoirs among people with HIV in the Rakai and Kyotera Districts in Uganda. Study participants were people whose HIV was suppressed by ART and had agreed to provide blood samples and receive a routine physical examination annually. People meeting study entry criteria continued to enroll each year. As part of this study, the team examined whether the introduction of dolutegravir-based regimens in 2018 had any effect on the makeup of HIV reservoirs in study participants. At the time of the published analysis, 63% of participants were female. The study observed that HIV reservoir size was generally decreasing as participants remained virally suppressed for longer periods. In the analysis of samples provided post-dolutegravir introduction, they observed a surprising 1.7-fold average increase in HIV reservoir size above pre-dolutegravir levels, which lasted for approximately a year, then returned to normal. This effect was consistent across the majority of study participants regardless of how long they had been living with HIV. 

According to the study authors, no other study has found significant differences in HIV reservoir characteristics due to ART regimen changes, but previous research has identified changes in immune characteristics and cardiovascular disease risk, as well as other effects in the period after dolutegravir initiation, suggesting the body goes through a period of adjustment when switching to use the new drug. The authors state that it is important to explore whether other populations experience the same temporary reservoir increase post-dolutegravir initiation, and that more research is needed to understand the mechanism causing the increase, especially if it is starting dolutegravir or stopping the previous ARV. They further suggest that these findings may inform HIV cure research, including approaches referred to as “Shock and Kill” that attempt to stimulate HIV reservoirs to resume activity, then promptly remove them. The authors did not observe any negative clinical ramifications, such as loss of viral control, associated with this finding.  

Most HIV reservoir research has been conducted among predominantly male study populations in Europe and North America, unlike the primarily female participants in this study. The authors highlight the importance of exploring sex-based differences in HIV reservoir characteristics and the inclusion of representative populations in HIV studies.

This research was conducted by NIAID, Western University, and the Rakai Health Sciences Program and with co-funding from other NIH institutes, the Gilead HIV Cure Grants Program, the Canadian Institutes of Health Research, and the Ontario Genomics-Canadian Statistical Sciences Institute.

Reference:

RC Ferreira, et al., Temporary increase in circulating replication-competent latent HIV-infected resting CD4+ T cells after switch to an integrase inhibitor based antiretroviral regimen. eBioMedicine DOI: 10.1016/j.ebiom.2024.105040 (2024)

Women account for approximately 23 percent of people with HIV in the United States. In recent years, women aged 25 to 34 comprised the highest number of new diagnoses. Furthermore, Black women, transgender women, and women aged 13 through 24 are more likely to experience health disparities associated with lack of access to HIV testing, treatment, and prevention resources. This weekend marked National Women and Girls HIV/AIDS Awareness Day. NIAID supports research programs that focus on HIV and other health outcomes in women to inform and enable more targeted and effective HIV prevention, care, and treatment.

American Women: Assessing Risk Epidemiologically (AWARE) 

The AWARE project aims to explore the multiple risks and vulnerabilities that lead to higher rates of HIV and other sexually transmitted infection (STI) acquisition in women, including transgender women. In the United States, the rate of new HIV diagnoses in Black women is about 14 times higher than their non-Black counterparts, and AWARE is designed to engage diverse racial and ethnic minorities, including Black women. AWARE is a national digital cohort with a primary goal of identifying women with greater likelihood of acquiring HIV and investigating contributing factors. The research group also seeks to design tailored and effective approaches to reaching women who reside in rural and underserved communities of color with HIV prevention and awareness resources. 

CAMELLIA Cohort: A Longitudinal Study to Understand Sexual Health and Prevention Among Women in Alabama 

The CAMELLIA Cohort supports cisgender and transgender women in Alabama who had a recent STI acquisitions and are impacted by disparities surrounding the lack of access to and the utilization of PrEP. The research program also uses a population-based approach to better understand how the quality of HIV and STI testing, in addition to HIV PrEP access, can be improved. CAMELLIA is sponsored by the University of Alabama at Birmingham in collaboration with NIAID and the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD).

HIV and Women at the 2024 Conference on Retroviruses and Opportunistic Infections (CROI)

At CROI 2024, NIAID-supported studies reported results on women-controlled HIV prevention and cardiovascular health in women with HIV:

• Pregnant people are three times more likely to acquire HIV than those who are not pregnant. The NIAID-sponsored DELIVER study, conducted by the Microbicide Trials Network, showed that the dapivirine vaginal ring and oral pre-exposure prophylaxis (PrEP) with tenofovir disoproxil fumarate and emtricitabine- were each safe for HIV prevention throughout pregnancy. The large clinical study was conducted in Malawi, South Africa, Uganda and Zimbabwe. Learn more about the DELIVER results presented at CROI. 
• A new analysis from the NIH-supported REPRIEVE trial found that the elevated cardiovascular disease risk among people with HIV is even greater than predicted by a standard risk calculator in several groups, including Black people and cisgender women. The study team concluded that updated tools are needed to facilitate precision, high-quality care of the diverse population with HIV. REPRIEVE enrolled 7,769 people with HIV across 12 countries, of whom 31% were women. Learn more about the REPRIEVE analysis presented at CROI, and the primary analysis that found pitavastatin reduced the risk of major adverse cardiovascular events by 35% in people with HIV. 

The NIH Office of AIDS Research (OAR) and Office of Research on Women’s Health (ORWH) jointly lead NIH’s HIV and Women Signature Program. The cornerstone of this new program is an intersectional, equity-informed, data-driven approach to research on HIV and women. The Signature Program advances the NIH vision for women's health, a world in which all women, girls, and gender-diverse people receive evidence-based care, prevention, and treatment tailored to their unique needs, circumstances, and goals. A new position paper, published February 26 in The Lancet HIV, outlines the framework for NIH's approach to research on HIV and women and highlights selected topics of relevance for women, girls, and gender-diverse people with or affected by HIV. The program also supports women in science careers to meet their full professional potential. From March 21-22, the OAR and ORWH will host the NIH HIV & Women Scientific Workshop: Centering the Health of Women in HIV Research. The workshop will review the state of the science on HIV and women to inform the future research agenda. Learn more.

The 2024 U.S. government theme for National Women and Girls HIV/AIDS Awareness Day is “Prevention and Testing at Every Age. Care and Treatment at Every Stage.” NIAID remains committed to advancing HIV research and prevention efforts for cisgender and transgender women alike. 

This blog is adapted and cross-posted from HIV.gov. 

On the final day of the 2024 Conference on Retroviruses and Opportunistic Infections (CROI), HIV.gov spoke with Deborah Persaud, M.D., professor of Pediatrics at the Johns Hopkins University School of Medicine and director of the Division of Pediatric Infectious Diseases at Johns Hopkins Children's Center, who reported findings from a study about whether very early initiation of antiretroviral therapy (ART) may limit the establishment of HIV reservoirs in newborns, potentially enabling ART-free remission. Dr. Persaud spoke with Catey Laube of NIAID’s Office of Communications and Government Relations. Watch their conversation below:

Four Children Achieve ART-free HIV Remission

The study Dr. Persaud presented at CROI began 10 years ago. HIV.gov spoke to Dr. Persaud at CROI 2013 when she presented the case of an infant born with HIV in Mississippi who initiated treatment at 30 hours of life, was taken off their ART at 18 months of age and remained in remission with no evidence of detectable HIV for 27 months. This was an uncommon finding because, typically, an interruption in treatment will lead to rapid resumption of HIV replication and detectable virus in the blood within weeks. Dr. Persaud and colleagues then began the NIH-supported study she reported on at CROI this year to carefully replicate that result in a research setting to determine whether the ART-free remission the “Mississippi baby” experienced was due to the very early start of HIV treatment within hours after birth and could be effective in other children.

Dr. Persaud reported on the experience of six children, all aged 5 years, who met multiple criteria to be eligible for a closely monitored ART interruption and whose parents consented. Four of the six children experienced HIV remission, defined as the absence of evidence of replicating virus for at least 48 weeks off ART. One of them had detectable HIV after 80 weeks. Two children did not experience remission, and their HIV became detectable within a few weeks after ART interruption. Children whose HIV became detectable resumed ART. The other three remain in remission. These promising findings will be followed by additional research to better understand the biological process that enabled the children to experience HIV remission off ART and to study early ART with newer drug regimens than were used in this initial study. Dr. Persaud cautioned that much more evidence is needed before this approach could be possible outside of the strictly monitored research setting. Read the study abstract. Read NIAID’s summary of the study findings.

Other Studies of Interest Presented on Wednesday

Some of the other NIH-supported research presented at CROI included a study that identified sex-based differences in latent HIV reservoirs, highlighting unique aspects of reservoirs in women. The findings point to the importance of including cisgender women in HIV cure studies. Read the study abstract. Another showed that a novel hepatitis B vaccine achieved up to 99% protection in people with HIV who had previously not responded to conventional hepatitis B vaccines. Read the study abstract.

Catch Up on More HIV Research Updates

HIV.gov has shared other interviews from CROI 2024 with federal HIV leaders, participating researchers, and community members. You can find all of them on HIV.gov’s social media channels and recapped here on the blog this week and next week.