A preventive vaccine for gonorrhea would be a major advance in public health, according to an editorial co-authored by NIAID Director Jeanne Marrazzo, M.D., M.P.H, and Myron Cohen, M.D., director of the Institute for Global Health and Infectious Diseases at the University of North Carolina at Chapel Hill. The editorial, published in the Journal of Infectious Diseases, provides context on new mathematical modeling projecting the cost-effectiveness of the meningitis B vaccine 4CMenB, which is currently being evaluated as a preventive intervention for gonorrhea. 

Gonorrhea, a common sexually transmitted infection, afflicts more than 80 million adults each year, according to the World Health Organization. It is caused by the Neisseria gonorrhoea bacterium. Untreated gonorrhea can lead to serious and permanent health conditions, such as pelvic inflammatory disease, painful swelling and blockages in male reproductive organs, and infertility. While usually treatable with antibiotics, N. gonorrhoeae bacteria have demonstrated resistance to most existing classes of antibiotics. The genetic sequences of N. gonorrhoeae and Neisseria meningitidis group B, the bacteria that can cause meningitis B, are closely related, which have led researchers to explore whether the 4CMenB vaccine, approved by the Food and Drug Administration for meningitis B, might also prevent gonorrhea. 

NIAID is sponsoring an efficacy study of the 4CMenB vaccine for gonorrhea prevention in more than 2,000 people aged 18-50 years in Malawi, Thailand, and the United States. The Kirby Institute is studying the same vaccine among gay, bisexual, and other men who have sex with men in Australia, and GlaxoSmithKline is studying a vaccine specifically designed to prevent gonorrhea, to assess its safety and potential efficacy. All studies are expected to report results within the next two years. 

The mathematical modeling published with the editorial was led by Imperial College London with funding through the Global Health EDCTP3 Joint Undertaking and the UK Health Security Agency. The model projected how the dosing, vaccine effectiveness, health promotion, and availability for those most likely to benefit could affect the cost effectiveness of 4CMenB vaccination for gonorrhea, showing a potential benefit even if efficacy is low in forthcoming study results. Models will be able to generate a more accurate cost-effectiveness estimate once efficacy studies are complete.

References

MS Cohen et al. What if We Had a Vaccine that Prevents Neisseria gonorrhoeae? Journal of Infectious Diseases DOI: 10.1093/infdis/jiae160 (2024)

D Nikitin et al. Cost-effectiveness of 4CMenB Vaccination Against Gonorrhea: Importance of Dosing Schedule, Vaccine Sentiment, Targeting Strategy, and Duration of Protection. Journal of Infectious Diseases DOI: 10.1093/infdis/jiae123 (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

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

On March 6 as the 2024 Conference on Retroviruses and Opportunistic Infections (CROI) was winding down, HIV.gov spoke with Carl Dieffenbach, Ph.D., director of NIAID's Division of AIDS, about highlights of long-acting HIV treatment research discussed at the conference. He spoke with Brian Minalga, M.S.W., deputy director of the NIH-supported Office of HIV/AIDS Network Coordination. Watch their conversation below:

Research Suggests Possible Expanded Options for Long-Acting HIV Treatment

Dr. Dieffenbach highlighted findings from several clinical trials and a plenary session presented at CROI about current and future options for long-acting antiretroviral treatment (ART) for HIV.

First, he discussed a NIAID-supported randomized clinical trial that found that long-acting ART with cabotegravir and rilpivirine was superior in suppressing HIV replication compared to daily oral ART in adults who had been unable to maintain viral suppression through an oral daily regimen. The LATITUDE study enrolled participants in 31 sites in the United States. Last month, the trial’s Data and Safety Monitoring Board conducted a planned review of interim data and recommended halting randomization and offering all eligible study participants long-acting ART based on its observed superior viral suppression of HIV. At CROI, study leaders reported that the interim analysis of data from 294 participants showed that the chance of experiencing unsuppressed HIV was 7% among people taking long-acting ART compared to 25% among those taking daily oral ART. The likelihood of discontinuing the assigned regimen due to adverse events or experiencing unsuppressed HIV was 10% among people taking long-acting ART compared to 26% among those taking daily ART. These findings were statistically significant. Dr. Dieffenbach observed that these results may support expanding the use of long-acting ART among a broader population. Read the study abstract. Read more in this NIAID news release.

Another ongoing clinical trial reported initial findings on the safety of the same long-acting injectable treatment regimen for adolescents with HIV with a suppressed viral load. The NIH-supported MOCHA study enrolled participants aged 12 to 17 who were virally suppressed in Botswana, South Africa, Thailand, Uganda, and the United States. In what he characterized as very encouraging results, Aditya Gaur, M.D. of St. Jude Children's Research Hospital, one of the trial’s co-chairs, reported that after the first six months all participants remained virally suppressed, and the level of the ART in their systems was comparable to what has been shown as efficacious in adult studies of the same drug. He also reported that, while about one-third of the participants reported an injection-site reaction, there were no surprising or unanticipated adverse events. These data support the use of cabotegravir and rilpivirine in virally suppressed adolescents, according to Dr. Gaur and colleagues. Dr. Dieffenbach noted that NIH will continue to support safety and dosing studies to determine the proper doses for adolescents and that these studies could eventually expand access to this long-acting HIV treatment to more people.
Read the abstract. Read NIAID’s news release about the study.

In addition, Dr. Dieffenbach mentioned an industry-sponsored Phase 2 trial that presented 24-week results of an oral once-weekly investigational combination of two drugs (islatravir and lenacapavir). Researchers reported that the investigational combination maintained a high level of viral suppression among study participants and was well tolerated. The study will continue to gather data and suggests that a weekly oral HIV treatment regimen could someday be possible. Read the abstract.

Finally, Dr. Dieffenbach discussed Wednesday’s plenary session by Charles Flexner, M.D. of The Johns Hopkins University School of Medicine, which was titled “The End of Oral? How Long-Acting Formulations Are Changing the Management of Infectious Diseases.” In his big picture, future-focused presentation exploring long-acting drug delivery, Dr. Flexner observed that there is a need for HIV products with less frequent dosing, greater convenience, and greater likelihood of viral suppression, as well as for the prevention and treatment of other diseases, including tuberculosis, malaria, and viral hepatitis. He discussed recent advances in formulation science that are going to help make available better replacements for daily oral drugs for HIV and many other infectious diseases. Dr. Dieffenbach underscored Dr. Flexner’s point that these novel products must be developed with access and equity in mind so that people who need them, especially in resource-limited settings, can use them.

Key Takeaways

Reflecting on key takeaways from the entire conference, both Dr. Dieffenbach and Brian pointed to the importance of partnership between the HIV community and scientists in all aspects of HIV research, a theme also discussed in HIV.gov’s conversation with Dr. LaRon Nelson from the conference. In terms of research highlights, Dr. Dieffenbach pointed to the results reported from the IMPAACT P1115 study in which several children who started HIV treatment within hours of birth later surpassed a year of HIV remission after a treatment pause. (See HIV.gov’s interview with Dr. Deborah Persaud about this study.) He also noted that the additional data accumulating on the effectiveness of Doxy-PEP is encouraging and will hopefully soon be reflected in clinical guidelines that help to reduce the incidence of syphilis, chlamydia, and gonorrhea in men who have sex with men and transgender women.

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 blog and social media channels.

About CROI

More than 3,600 HIV and infectious disease researchers from 73 countries gathered in Denver and virtually from March 3-6 this year for CROI, an annual scientific meeting on the latest research that can help accelerate global progress in the response to HIV and other infectious diseases, including STIs and viral hepatitis. Over 1,000 summaries of original research were presented. Visit the conference Web site for more information. Session webcasts and more information will be published there for public access.

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.