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.

Research by NIAID grantees strongly suggests that immune responses to a newly discovered species of gut bacteria may cause some cases of a common autoimmune disease called rheumatoid arthritis, or RA. The findings were recently published in Science Translational Medicine.

In people with RA, their own antibodies and T cells attack their joints, especially in the hands, wrists, and knees. This leads to inflammation, pain, and swelling in the joint lining. Over time, RA progresses to irreversible joint tissue damage, chronic pain, loss of function, and deformities. Scientists do not know what causes RA despite extensive efforts to understand the earliest stages of this disease.  

Some RA research has focused on understanding what triggers the development of the antibodies and T cells that attack the joints. Several studies have suggested that the production of joint-targeting antibodies starts at mucosal surfaces, such as the lining of the mouth, airways, and gut, more than a decade before symptoms arise and might be stimulated by bacteria at these sites. Until now, however, the bacterial culprit remained unknown.

In the new study, investigators isolated antibody-secreting cells called plasmablasts from the blood of people at risk for RA and found that the antibodies produced by these cells recognized certain bacteria in the gut microbiome of these individuals. The researchers identified a previously unknown bacterial species targeted by these antibodies, which they named Subdoligranulum didolesgii. This bacterium was present in the feces of four out of 24 people who were either at risk for or diagnosed with RA but absent from the feces of 12 healthy people.

The scientists hypothesized that a mucosal immune response to S. didolesgii in the gut might progress to a body-wide immune response. To test their hypothesis, the researchers gave mice an oral dose of the bacterium and monitored their immune and physical responses. The mice developed antibodies and T cells that attacked their joints and led to visible joint swelling. In addition, the immunologic changes that the scientists observed in the mice extended over time from the gut mucosa to sites throughout the body. 

Taken together, the findings suggest that in some people with RA, immune responses to S. didolesgii in the gut may trigger the production of antibodies and T cells that circulate throughout the body and attack the joints, leading to chronic inflammation. Thus, it appears that RA may develop because immune-system targets shared by S. didoglesgii and joint tissue have a similar structure or amino-acid sequence.

Didolesgi is the Cherokee word for arthritis or rheumatism and was proposed as the name for the newly discovered bacterium by the study’s first author, Meagan E. Chriswell, B.S., who is an enrolled member of the Cherokee Nation of Oklahoma. Ms. Chriswell, an M.D./Ph.D. candidate in immunology at the University of Colorado Anschutz Medical Campus in Aurora, and Kristine A. Kuhn, M.D., Ph.D., an associate professor of medicine at the university, led the research. 

The study was co-funded by NIAID and the National Institute of Arthritis and Musculoskeletal and Skin Diseases, both part of the National Institutes of Health.

Reference: ME Chriswell, et al. Clonal IgA and IgG autoantibodies from individuals at risk for rheumatoid arthritis identify an arthritogenic strain of Subdoligranulum. Science Translational Medicine DOI: 10.1126/scitranslmed.abn5166 (2022).

To reduce the spread of HIV infection, the World Health Organization (WHO) recommends pre-exposure prophylaxis (PrEP) in populations with an annual HIV infection incidence greater than 3%. Given that the annual HIV incidence in Uganda is estimated at 0.40% (0.46% among females and 0.35% among males), there are people who may have a higher HIV risk and may benefit from PrEP but are not targeted for services. To further reduce the spread of HIV in Uganda, researchers used results from three survey rounds of HIV-negative participants within the Rakai Community Cohort Study (RCCS) to estimate the prevalence of high-risk individuals eligible for PrEP within the general population and the incidence of HIV infection associated with eligibility. 

In this study, a subset of questions from Uganda’s PrEP eligibility tool that are routinely asked within the RCCS surveys were used to determine PrEP eligibility. Eligibility was defined as reporting at least one of the following HIV risk behaviors in the past 12 months: sexual intercourse with more than one partner of unknown HIV status; nonmarital sex act without a condom; sex engagement in exchange for money, goods, or services; or experiencing genital ulcers. HIV incidence was estimated by analyzing seroconversion from HIV-negative to HIV-positive in participants who contributed to at least two of the survey rounds.

Overall, 29% of participants in the analysis met the eligibility criteria. Of these, 22% reported one HIV risk, 6% reported two HIV risks, and 1% reported three HIV risks. The results showed that PrEP eligible participants had twice the risk of acquiring HIV than their non-eligible counterparts. Furthermore, risk increased threefold in uncircumcised males but not circumcised males. Additionally, men who reported higher prevalence of risky behaviors had lower increase in HIV incidence compared to women, likely due to circumcision status and higher antiretroviral therapy coverage in HIV-infected females, leading to a decrease in transmission to men. The findings of this study support the use of PrEP eligibility screening in general populations with HIV incidence lower than 3% to reduce HIV acquisition even further in these populations.

Reference: Ssempijja et al. High Rates of Pre-exposure Prophylaxis Eligibility and Associated HIV Incidence in a Population With a Generalized HIV Epidemic in Rakai, Uganda, JAIDS Journal of Acquired Immune Deficiency Syndromes, July 1, 2022 - Volume 90 - Issue 3 - p 291-299.