Despite the high HIV burden among transgender women, access to health care among this demographic is low due to structural barriers that limit access to HIV prevention, testing, care, and other health services. Therefore, transgender women have been identified as a priority population in the Ending the HIV Epidemic in the U.S. (EHE) plan and National HIV/AIDS Strategy.

In this study, a multisite cohort was used to estimate HIV incidence in 1,312 transgender women in the eastern and southern regions of the United States. This approach allowed for monitoring epidemic trends, identifying drivers of HIV acquisition, and assessing if and how national health policies and HIV prevention efforts, including new pre-exposure prophylaxis (PrEP) modalities, affect HIV epidemic trends. The multisite cohort was established across two modes: 1) a site-based, technology-enhanced mode in six cities and 2) an exclusively digital mode that covered 72 cities. An advantage of including both a site-based and a digital mode is that it allowed for testing of the digital divide concept. For example, participants with technology access may have higher levels of education and few economic vulnerabilities, factors that have been associated with lower HIV incidence rates in previous studies. Adult transwomen (≥18 years) who were not living with HIV were eligible for inclusion and were followed up for at least 24 months, with some participants re-enrolling for an additional 3 years. Participants completed surveys and oral fluid HIV testing with clinical confirmation.

The findings of this study revealed that HIV incidence was higher in the site-based mode than in the digital mode. Paired with the finding that inconsistent access to communication technology was also associated with incidence rates, the study supports the digital divide concept. Experiences and characteristics associated with HIV incidence included race, self-reported history of sexually transmitted infection, stimulant use, telephone disconnection, number of recent sexual partners, PrEP indication, and partner PrEP use.  Even though digital and telehealth options have become increasingly common, community and location-based efforts are still needed to reach the most marginalized transgender women. Structural, individual-level, and substance use interventions may be instrumental in improving access to various health services, including HIV prevention and mental and behavioral health services.

References:

Wirtz, AL et al. HIV incidence and mortality in transgender women in the eastern and southern USA: a multisite cohort study. Lancet HIV. DOI 10.1016/S2352-3018(23)00008-5

The growing uptake of antiretroviral therapy (ART) has resulted in an increase in the lifespan of persons with HIV (PWH); however, aging-related non-AIDS comorbidities (NACM) are now on the rise and present a new health challenge. PWH have a higher burden of comorbidities and these comorbidities begin earlier than in the general population. Furthermore, data suggests that there are stark sex differences in NACM risk and severity. The increased burden of comorbidities can lead to reduced quality of life, premature mortality, and increased health care needs and spending. A better understanding of the differences in presentation and incidence of NACM in men and women living with HIV will inform better intervention approaches for this growing public health concern.

This cross-sectional study examined the differences in burden of NACM in women and men with and without HIV to assess distribution and severity. The analysis included approximately ten years of data from women and men enrolled in HIV/AIDS cohort studies and similar individuals who are seronegative for HIV for comparison. Ten aging-related NACM were examined (hypertension, dyslipidemia, diabetes, cardiovascular disease, kidney disease, liver disease, lung disease, bone disease, psychiatric illness, and non-AIDS cancer). The burden and prevalence of these comorbidities were the primary measures of the study. The most prevalent NACM in PWH were found to be hypertension, psychiatric illness, dyslipidemia, liver disease, and bone disease. Prevalence of bone disease, lung disease, and diabetes was higher in women than men. Consistent with findings from other studies, the overall burden of aging-related comorbidities was higher in women than men, particularly among PWH.

The findings of this study support the need to further define the distribution and severity of NACM by sex and gender to improve strategies to support healthy aging in PWH. Clinical guidance and tools are needed to accurately identify PWH at risk of multimorbidity to offer more timely interventions. Additional research is needed to further understand the impacts of HIV and aging across the lifespan for women, including the effects of menopause transition on the progression of comorbidities.

References:

Collins, LF et al. Aging-Related Comorbidity Burden Among Women and Men With or At-Risk for HIV in the US, 2008-2019. JAMA Netw Open. DOI 10.1001/jamanetworkopen.2023.27584

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

As syphilis rates continue to rise in the United States, emergency departments may be a way for people with limited healthcare access to get screening and treatment. A NIAID study derived an emergency department syphilis screening strategy to help people get diagnosed before their infection reaches an advanced stage. This approach could reduce disease burden and prevent cases of congenital syphilis, in which the bacteria are passed from a birth parent to their infant. The findings were published today in Open Forum Infectious Diseases. 

Syphilis, caused by the bacteria Treponema pallidum, is a common sexually transmitted infection (STI). Untreated syphilis can cause nervous system and organ damage, as well as pregnancy complications for birth parents and their infants. In the United States, adult and congenital syphilis cases have increased by 78.9% since 2018, with a drastic 17% increase in 2022 alone. The syphilis surge has disproportionately burdened historically and medically underserved populations. These health disparities underscore the need for greater access to syphilis testing and treatment resources. 

Researchers analyzed blood samples retrospectively from 1,951 adults who presented to a Baltimore emergency department over the course of a month in early 2022. They found 103 people (5.3%) had detectable treponemal antibodies to syphilis, which are indicative of a previous or active syphilis infection. Of them, 23 people (22%, 1.1% overall) had high non-treponemal antibody levels, which indicate active syphilis. The study investigators prioritized identifying people with active syphilis and performed statistical analyses to determine the associated risk factors to inform a potential screening strategy.  

The proportion of samples with active syphilis was highest among people with HIV and people without a primary care provider. Among women with active syphilis, eight out of nine (88%) were between the ages of 18 and 49 years, which is defined as the window of reproductive age. Statistical analyses demonstrated that screening people living with HIV, without a primary care physician, and women aged 18 to 49 years would have identified 21 of the 23 people (91%) with active syphilis in the participating emergency department.

Typically, emergency departments only screen people for syphilis if they present with symptoms consistent with primary or secondary syphilis. According to the authors, the findings demonstrate the advantages of conducting focused syphilis screening during routine emergency department visits, particularly for communities who may have limited access to health care. They suggest that implementing a screening strategy informed by this study could help address the underdiagnosis of syphilis while expanding the reach of effective prevention and treatment, reducing the burden of adult and congenital syphilis. Finally, the continued syndemic of HIV and syphilis—two epidemics that interact with each other, with adverse effects on the health of communities—highlights the opportunity to provide comprehensive HIV and STI prevention and care in the emergency department, where people with high incidence frequently seek care. 

Reference: 

J Hunt, et al. A Potential Screening Strategy to Identify Probable Syphilis Infections in the Urban Emergency Department Setting. Open Forum Infectious Diseases. DOI: https://doi.org/10.1093/ofid/ofae207 (2024).

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).