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

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

During the first full day of presentations at the 2024 Conference on Retroviruses and Opportunistic Infections (CROI), HIV.gov spoke with Carl Dieffenbach, Ph.D., director of NIAID’s Division of AIDS, about research presented on Doxy-PEP for sexually transmitted infections (STIs) and HIV vaccines. He spoke with Louis Shackelford of the HIV Vaccine Trials Network. Watch their conversation.

Louis also spoke with LaRon Nelson, Ph.D., R.N., F.N.P., F.N.A.P., F.N.Y.A.M., F.A.A., about community-engaged research, HIV prevention at CROI, and a new study (HPTN 096) he is leading to reduce HIV rates among Black men who have sex with men (inclusive of cisgender and transgender men) in the southern United States. Dr. Nelson is a professor and the associate dean at the Yale School of Nursing. Watch their conversation.

Insights from Doxy-PEP Use in Real World Settings

At last year’s CROI, researchers presented results from an NIH-supported study on using a preventive dose of the antibiotic doxycycline as post-exposure prophylaxis within 72 hours after condomless sex to prevent bacterial STIs, an approach that has become known as Doxy-PEP. (View last year’s Doxy-PEP discussion with Dr. Dieffenbach.) Here at CROI 2024, Dr. Annie Luetkemeyer of the University of California, San Francisco, shared additional findings from the open-label extension of that original study, which found sustained reduction of bacterial STIs among men who have sex with men and transgender women living with HIV or on PrEP in Seattle and San Francisco. The San Francisco AIDS Foundation (SFAF) was one of the first organizations in the United States to roll out Doxy-PEP, beginning in late 2022 when it was offered to all active PrEP clients at their visits at the Magnet clinic. SFAF medical director Dr. Hyman Scott reported that there was high uptake among clients and that bacterial STIs decreased by nearly 60% in less than a year at SFAF’s clinic. The decline was highest for syphilis (78%) and chlamydia (67%).

The San Francisco Department of Public Health (SFDPH) presented the first findings to measure the effect of Doxy-PEP at the population level. Their analysis, presented by epidemiologist Madeline Sankaran, showed a substantial and sustained decline in the number of chlamydia and early syphilis infections in San Francisco among men who have sex with men and transgender women over the 13 months after the Department released guidelines for the use of Doxy-PEP. As in the other studies presented, SFDPH did not see corresponding significant declines in gonorrhea. Doxy-PEP is not recommended for cis-gender women because there is not yet evidence to suggest it is effective for them.

HIV Vaccine Trials Continue

Dr. Dieffenbach also discussed ongoing research to find a vaccine to prevent HIV, the topic of several presentations at the conference so far. Since there are a number of Phase I HIV vaccine trials currently underway, he and Louis spoke about what those smaller trials do. Then they discussed what some of the HIV vaccine trials currently underway are exploring.

Other Studies of Interest Presented on Monday

Some of the other studies presented centered on broadly neutralizing antibodies (bNAbs), including bNAbs as part of HIV therapy and how different HIV variants can affect bNAb efficacy as a treatment method. A new analysis from the pivotal HVTN 083 study of long-acting PrEP with cabotegravir found no significant risk of hypertension in people using the method, which had been a concern in some previous clinical studies of the same class of antiretroviral drugs.

Community-Engaged Research

The importance and significant benefits of involving community in all aspects of HIV research was the first topic Dr. Nelson and Louis discussed. “If we don’t have community voices or engaged communities, we aren’t going to be asking the right questions or designing the studies in the best ways that will produce the outcome that we need, and we won’t end up with answers that are as relevant as they could be,” Dr. Nelson observed. He pointed to the dapivirine vaginal ring as an example of better outcomes because communities were involved in research. He said he hopes that community engagement in research continues to become more and more common, but it requires that researchers be willing to listen and, when needed, change their plans based on what they hear from community.

HIV Prevention Research at CROI

Dr. Nelson highlighted some of the HIV prevention topics at CROI that have caught his attention, such as increasing equitable use of long-acting injectable forms of HIV PrEP and treatment among different populations and in different countries. Other discussions of interest have included early studies on potentially very long-acting forms of HIV PrEP and exploration of possible dual prevention tools that would provide users with both HIV PrEP and contraception.

HPTN 096 Study

Finally, Dr. Nelson discussed an example of community-informed research that will soon be underway: the NIH-supported study through the HIV Prevention Trials Network (HPTN) known as HPTN 096. It aims to reduce HIV rates among Black men who have sex with men in the southern United States using a strategy developed based on what communities have told Dr. Nelson and colleagues is needed to do so. As a result, the study includes a package of four interventions which simultaneously address social, structural, institutional, and behavioral barriers to HIV prevention and care. HPTN 096 will soon launch in Atlanta, south Florida, Montgomery, Memphis, and Dallas.

More HIV Research Updates to Follow on HIV.gov

HIV.gov will be sharing additional video interviews from CROI 2024 with Dr. Dieffenbach, CDC’s Dr. Jono Mermin and Dr. Robyn Neblett Fanfair, and others. You can find all of them on HIV.gov’s social media channels and recapped here on the blog.

During the first full day of research presentations at the 2023 Conference on Retroviruses and Opportunistic Infections (CROI), HIV.gov spoke with Dr. Carl Dieffenbach, Director of the Division of AIDS at NIH’s National Institute of Allergy and Infectious Diseases (NIAID), about some initial highlights, including the opening session that featured a lecture by Dr. Anthony Fauci and several studies about the use of doxycycline for post-exposure prophylaxis (Doxy-PEP) for sexually transmitted infections (STIs). Watch our conversation with Dr. Dieffenbach below:

Dr. Fauci Reflects on the History of HIV
The opening session celebrated the 30th anniversary of this conference, and Dr. Dieffenbach observed that history was a throughline in several of the opening lectures. Dr. Anthony Fauci, who recently stepped down as Director of NIAID, a position he held since 1984, presented a talk titled “CROI: A 30-Year Chronicle of HIV/AIDS Research Progress,” in which he highlighted several “wow” moments from the history of our understanding of and response to HIV and AIDS and recalled how many significant advances were presented at this conference over the years. Dr. Kevin De Cock traced the history of HIV in Africa, and Yvette Raphael of South Africa reflected on the evolution of the response to HIV among women, particularly in sub-Saharan Africa where they are the most affected population, as well as the vital role of activism and community involvement in clinical trials.

Post-Exposure Prophylaxis for STIs
Dr. Dieffenbach also highlighted three new studies that provided additional information about using a preventive dose of the antibiotic doxycycline within 72 hours after condomless sex to prevent bacterial STIs. First, the DoxyVAC study, presented by Dr. Jean-Michel Molina of the University of Paris Cité, assessed two different strategies to reduce the burden of STIs among gay men on HIV PrEP who had a history of an STI in the prior year. The researchers set out to confirm a previous finding on the effectiveness of the Doxy-PEP strategy and assess whether a second (independent) intervention with the meningococcal B vaccine could also have an impact on gonorrhea incidence. The researchers found that Doxy-PEP significantly reduced the incidence of chlamydia and syphilis and had a significant impact on the incidence of gonorrhea and that the meningococcal B vaccine reduced the incidence of gonorrhea by roughly 50% in the participants who received two doses. Dr. Dieffenbach shared that NIAID is also supporting an ongoing large-scale clinical trial at three sites in the southeast United States studying whether the meningococcal B vaccine also can protect participants from infection with the bacteria that causes gonorrhea.

Dr. Anne Luetkemeyer of the University of California, San Francisco, presented additional data from the Doxy-PEP study that had previously demonstrated the effectiveness of the intervention among men and transgender women who have sex with men. The data she presented helped answer the question of whether this use of doxycycline might cause antimicrobial resistance in the bacterial STIs it is intended to prevent. Her analysis found there was no marked increase in doxycycline resistance among three key bacteria, including gonorrhea and Staphylococcus aureus, which can cause diseases.

However, as Dr. Dieffenbach discussed, a study from Kenya presented by Dr. Jenell Stewart of the University of Minnesota indicates that Doxy-PEP may not be effective for women. The study of 449 young cisgender women who were using PrEP found that the use of Doxy-PEP following condomless sex did not reduce incident STIs in this population. She noted that the findings raised questions for further exploration, such as whether the ineffectiveness of Doxy-PEP in this study could be due to differing drug concentrations in vaginal/cervical tissue vs rectal tissue, low adherence, or antimicrobial resistance.

About CROI
CROI is an annual scientific meeting that brings together leading researchers and clinical investigators from around the world to present, discuss, and critique the latest studies that can help accelerate global progress in the response to HIV and AIDS and other infectious diseases, including viral hepatitis, COVID-19, and mpox. More than 3,400 HIV and infectious disease researchers from 72 countries are gathered in Seattle and virtually this year for this forum. Among the studies that are being presented are many that were conducted or supported by NIH, CDC, and other federal agencies. Visit the conference website for more information; abstracts, session webcasts, and e-posters will be published there for public access in 30 days.