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Cherabie, MD, MSc, is medical director of the St. Louis STI/HIV prevention Training Center, and the medical director of the WashU PrEP Clinic.

Joseph Cherabie MD, MSc, explains the importance of how these 2 components go hand-in-hand, and what it means to continue forward in spite of being in an unpredictable time. 

HIV Education and Advocacy in an Age of Uncertainty

Along with a 1 reported case in Massachusetts, the

New Hampshire Department of Health and Human Services (DHHS) has confirmed a person infected with eastern equine encephalitis (EEE) has died. The public health agency said the person was hospitalized due to severe central nervous system disease. The last reported human EEEV infection in New Hampshire was in 2014, when DHHS identified 3 human infections, including 2 fatalities. In the same statement, DHHS mentions there has been 1 confirmed case in Vermont this summer.

On August 16, the Massachusetts Department of Public Health (MDPH) released a statement discussing the confirmation of the first human case of EEE in the state this year. The confirmed case was discovered in an 80 year old man who was exposed to the vector borne disease in Worcester County. As a result, the risk level in the local communities of Douglas, Oxford, Sutton, and Webster has been raised to critical, and in Dudley, Northbridge, and Uxbridge the risk is increased to high.

Additionally, the neighboring communities of Auburn, Charlton, Grafton, Leicester, Mendon, Millbury, Millville, Southbridge, and Upton are now considered at moderate risk according to MDPH.

“This is the first time we have seen a person infected with EEE in Massachusetts since 2020,” Public Health Commissioner Robbie Goldstein, MD, PhD, said in a statement. “EEE is a rare but serious disease and a public health concern. We want to remind residents of the need to protect themselves from mosquito bites, especially in areas of the state where we are seeing EEE activity.

Though very rare, EEE is serious and a potentially fatal disease that can affect people of all ages. EEE is generally spread to humans through the bite of an infected mosquito. There were 12 human cases of EEE in Massachusetts in 2019 with 6 deaths, and 5 human cases with 1 death in 2020. There were no human cases of EEE in Massachusetts in 2021, 2022, or 2023.

EEE has a fatality rate of 33% to 70%, with most deaths occurring 2–10 days after the onset of symptoms.

In addition to a high mortality rate, long-term physical and mental complications, including permanent neurological deficits have been identified in many people who survive EEE.

Plymouth is approximately 40 miles south of Boston along the coast, and Worcester County is in the middle of the state, so the 2 areas are not in close proximity, but due to the elevated risk locally, the town of Plymouth decided to take action in response to outdoor parks. As of last Friday, all town public parks and fields are close daily from dusk until dawn.

“As Mass DPH has now elevated Plymouth’s EEE risk status to high, it is important to take extra precautions when outdoors and follow state and local health guidelines to avoid unnecessary risk to exposure to EEE. The health and safety of our community, residents, and visitors remain our priority,” Plymouth’s Commissioner of Health and Human Services, Michelle Bratti, said in a statement.

According to the Centers for Disease Control and Prevention (CDC) most people who are infected with the virus do not develop symptoms; however, for those that do, the date from the bite to the onset of the illness is 4 to 10 days. EEE can also result in fever or neurologic disease. The type of illness will depend on the age of the person and other factors. Those who are infected can develop meningitis.

There are no FDA-approved treatments for EEE and for patients who develop severe cases, they can be hospitalized to receive supportive treatment.

Over the weekend, MDPH detailed plans of spraying for mosquitos including aerially in areas of Plymouth County, and truck-mounted spraying in parts of Worcester County. As of Saturday, 10 communities in Massachusetts were raised to high or critical risk for EEE virus.

“The risk from EEE is high in parts of Plymouth County and critical in parts of Worcester County,” State Epidemiologist Catherine M. Brown, DVM, said in a statement. “In addition to recommending that people use mosquito repellent with an EPA-registered active ingredient and clothing to reduce exposed skin, we also recommend that evening outdoor events be rescheduled to avoid the hours between dusk and dawn. The mosquitoes most likely to spread EEE are most active during the dusk to dawn hours.”

There are preventative strategies to avoid EEE, and the MDPH has listed such measures 

For those who live in Massachusetts and want more information on EEE, it can be found 

 or by calling the DPH Division of Epidemiology at 617-983-6800.

1.NH DHHS Identifies Person Infected with Eastern Equine Encephalitis Virus in New Hampshire.The New Hampshire Department of Health and Human Services. August 27, 2024. Accessed August 28, 2024.
https://www.dhhs.nh.gov/news-and-media/nh-dhhs-identifies-person-infected-eastern-equine-encephalitis-virus-new-hampshire
2. State health officials announce season’s first human case of Eastern Equine Encephalitis in Massachusetts. MDPH. August 16, 2024. Accessed August 27, 2024.
https://www.mass.gov/news/state-health-officials-announce-seasons-first-human-case-of-eastern-equine-encephalitis-in-massachusetts
3.Plymouth to Close all Public Parks and Fields from Dusk to Dawn. Town of Plymouth. August 23, 2024. Accessed August 27, 2024. PDF.
4. Eastern Equine Encephalitis: Symptoms, Diagnosis, and Treatment. CDC. May 15, 2024. Accessed August 27, 2024.
https://www.cdc.gov/eastern-equine-encephalitis/symptoms-diagnosis-treatment/index.html
5. State officials announce plans to spray for mosquitoes in sections of Worcester and Plymouth counties due to EEE. MDPH. August 24, 2024. Accessed August 27, 2024. 
https://www.mass.gov/news/state-officials-announce-plans-to-spray-for-mosquitoes-in-sections-of-worcester-and-plymouth-counties-due-to-eee



The town of Plymouth decided to prohibit people from using the parks from dusk to dawn due to concerns over eastern equine encephalitis after a man contracted the rare disease in the state.

Concerns Over Mosquito-Borne Illness Causes Massachusetts Town to Create Curfew for Parks, Spraying in Counties

Annie Antar, MD, PhD, offers some insights as to why some individuals develop this condition.  

Does Slow Viral Clearance and Viral Rebound During Infection Contribute to Long COVID?

The pathogenesis in how Long COVID developing remains a mystery and truly undefined as to why some people become afflicted by this condition and why others do not. However, investigators are gathering clues towards increasing evidence of how it takes hold.

Annie Antar, MD, PhD, assistant professor of medicine, Johns Hopkins University School of Medicine believes there are 2 ways in which Long COVID might develop and they might be related. She has been examining how delayed viral clearance and viral rebound during acute COVID contribute to the development of Long COVID.

“I think what might be happening is there might be a two-hit hypothesis, where you have one hit, which is like you're in the minority of people who happen to have virus persist, but then something else happens, and then that's triggering you to develop the syndrome of Long COVID, while other people who have virus persisting don't feel the same way,” Antar said.

Antar and coinvestigators studied the relationship between severe COVID-19 viral dynamics during infection. Their findings were published in 

“We observed that slower viral clearance rates during acute COVID-19 were associated with increased risk and more symptoms of Long COVID. Early viral-host dynamics appear to be mechanistically linked to the development of Long COVID,” Antar and her coauthors wrote.

In terms of biomarkers to help predict Long COVID risk, Antar believes IgA autobody response could be one that is involved, but she acknowledges it could be multifactorial.

“I do think that probably IgA antibody response is a big part of that. There are other parts of your immune system that are involved in clearing virus and viral antigen, things like macrophages, can clear viral antigen from the tissue and destroy it, and also help prompt more of an immune response. So it could be antibody responses, it could be weakened T cell responses, it could be weakened kind of innate responses, things like macrophages that it should be patrolling. So I think all those things are probably involved. And, in terms of biomarkers, the virus itself is a great biomarker," Antar said.

Ultimately, the understanding of the pathogenesis is still undetermined, but they are getting closer to understanding it. Antar will presenting data from her published paper at 

, held March 9-12, in San Francisco, California.

1.Herbert C, Antar AAR, Broach J, et al. Relationship Between Acute SARS-CoV-2 Viral Clearance and Long COVID-19 (Long COVID) Symptoms: A Cohort Study. 

. 2025;80(1):82-90. doi:10.1093/cid/ciae539

Annie Antar, MD, PhD, offers insights around her research on her findings on this subject.

Conferences

Nilu Goonetilleke, LLBHons, BScHons, presents findings from the Phase I study, showing a 50% reduction in T cell response with age, while 85% of participants demonstrated strong immune responses.

The M&M Study: Age-Related T Cell Response in People with HIV on ART in MVA.HIVconsvX Vaccine Trial

, held March 9-12, in San Francisco, California, Nilu Goonetilleke, LLBHons, BScHons, PhD, associate professor at UNC School of Medicine, discussed The M&M Study, a Phase I trial investigating the MVA.HIVconsvX vaccine. The vaccine uses a Modified Vaccinia Ankara (MVA) vector to express HIVconsvX immunogens and aims to induce HIV-specific T-cell responses. The study examined the impact of age on immune responses to the vaccine in people with HIV (PWH) on ART, which suppresses but does not cure the infection. The results showed that while age was associated with a reduced T-cell response, the vaccine was safe and induced T-cell responses across all age groups.

The study found that vaccination increased HIV-specific T-cell responses in PWH on ART, with 11% of participants showing new responses. The magnitude of the T cell response decreased with age, showing a 50% reduction over a 20-year period. Longer ART duration was positively associated with stronger T-cell responses, suggesting ART may help mitigate age-related immune decline. Virological assessments showed no significant changes in low-level viremia or total integrated DNA, though a modest increase in intact integrated DNA was observed.

This was a double-blind, randomized trial. There were 21 participants on ART for at least 24 months with CD4 counts above 350 cells/mm³ were vaccinated with MVA-based vaccines expressing Mosaic-1 (M3), Mosaic-2 (M4), or both (M3+M4), or a placebo. T-cell responses were assessed using IFN-γ ELISpot assays, and virological endpoints, including low-level viremia and integrated DNA, were evaluated. Linear regression was used to analyze the impact of age and ART duration on vaccine-induced T-cell responses.

The MVA.HIVconsvX vaccine demonstrated a strong safety profile, with all adverse events being mild and resolving within 24 hours. Goonetilleke explained, “These are what we describe as viral-vectored vaccines, and the MVA used in this study is an attenuated virus that cannot replicate. It’s been tested in elderly individuals and newborns and has always been shown to be safe.”

The study revealed that older individuals had a lower T-cell response to the vaccine. Goonetilleke discussed this finding, “It is well documented that as we age, our immune response generally weakens. For T-cell vaccines like the MVA.HIVconsvX, our bodies become less capable of producing a broad and diverse range of T-cells, which is vital for the success of vaccination.”

Goonetilleke also pointed out that longer durations on ART were linked to better immune responses. She said, “What was particularly interesting about this study was that people who had been on ART for a longer period had better immune responses, which suggests that ART may help mitigate the effects of aging on immune function.”

Goonetilleke remains optimistic about the potential for future HIV vaccines. She highlighted that the MVA.HIVconsvX vaccine induced a robust immune response in nearly 85% of participants, regardless of their age, which suggests strong potential for widespread vaccine applicability. “This is a vaccine designed to target the conserved regions of HIV, which is promising because it can work across a diverse population of PWH,” she said.

Looking ahead, Goonetilleke noted that strategies such as booster doses or modified vaccination regimens could enhance the immune response, particularly for older individuals. “For people who are older, we’re looking at doing boosting vaccinations or modifying the vaccine to better focus the immune response against HIV.”

Goonetilleke N, et al. Age inversely correlates with T-cell response to MVA.HIVconsvX vaccination in PWH on ART. Poster #425 presented at CROI 2025. March 9-12, 2025, San Francisco, California.

Nilu Goonetilleke, LLBHons, BScHons, presents findings from the phase 1 study, showing a 50% reduction in T cell response with age, while 85% of participants demonstrated strong immune responses.

At CROI 2025, Nilu Goonetilleke, LLBHons, BScHons, PhD, presents findings showing the bivalent HIVconsvX vaccine targets both Mosaic-1 and Mosaic-2, resulting in broader immune responses.

The CM Study: Bivalent HIV Vaccine Induces Stronger T Cell Responses in People with HIV on ART

, held March 9-12, in San Francisco, California, Nilu Goonetilleke, LLBHons, BScHons, PhD, associate professor at UNC School of Medicine, discussed The CM Study, a phase 1 trial investigating the ChAdOx1 and MVA-based HIVconsvX vaccine. The vaccine uses viral vectors to express the HIVconsvX immunogens, Mosaic-1 and Mosaic-2, and aims to induce HIV-specific T-cell responses in people with HIV (PWH) on ART. The study hypothesized that the bivalent regimen, including both immunogens, would elicit a stronger and broader T-cell response than the monovalent regimen. The findings showed that the bivalent vaccine induced a significantly greater T-cell response targeting both immunogens, supporting the hypothesis that a broader immune response could be achieved.

The study found that the monovalent (C62-M4) and bivalent (C1C62-M3M4) vaccine regimens were safe, with mild adverse events that resolved within 24 hours. The bivalent vaccine, which targets Mosaic-1 and Mosaic-2, induced higher T-cell responses, especially to Mosaic-1, at days 140 and 196, indicating a more sustained and broader immune response. The placebo group showed no significant changes in T-cell frequency.

This was a double-blind, randomized trial with participants on ART for at least 24 months and CD4 counts above 350 cells/mm³. The participants were divided into three groups: 

Group 1 received the monovalent vaccine (C62-M4)

Group 2 received the bivalent vaccine (C1C62-M3M4)

T-cell responses were measured using IFN-γ ELISpot assays, and virological endpoints, including low-level viremia and integrated DNA, were assessed. Linear regression was used to analyze the effect of ART duration on vaccine-induced T-cell responses.

Goonetilleke emphasized the safety profile of the vaccines, saying, “Both the MVA and ChAdOx1 vectors are attenuated viruses, meaning they cannot replicate. These viral vectors have been used safely in a variety of populations, including in smallpox vaccination and more recently in COVID-19 vaccines.”

Regarding the bivalent vaccine's effectiveness, Goonetilleke explained, “The bivalent regimen induced broader immune responses because it targets two different conserved regions of HIV. This could be crucial, as HIV is highly diverse and using multiple immunogens may help cover the variety of viral strains circulating within individuals.”

The study also revealed that participants in the bivalent group showed a stronger and more sustained immune response, particularly to Mosaic-1. Goonetilleke noted, “The bivalent vaccine produced responses to both Mosaic-1 and Mosaic-2, which suggests it could be more effective at targeting the diversity within the HIV reservoir.”

Looking ahead, Goonetilleke is optimistic about the implications for ART-free remission strategies. She added, “The fact that the bivalent vaccine induced a strong T-cell response in a small group of participants suggests that this approach could contribute to HIV cure strategies, especially in combination with other treatments.”

Future steps for this research include evaluating the vaccine’s effect on the HIV reservoir, with plans for post-hoc analyses to explore how age and ART duration impact T-cell responses. Goonetilleke concluded, “We are excited about further studies to refine these vaccines, especially in exploring how they can support ART-free remission for individuals living with HIV.”

Goonetilleke N, et al. ChAdOx1.HIVconsvX and MVA.HIVconsvX vaccination is safe and immunogenic in PWH on ART: The CM Study. Poster #428 presented at CROI 2025. March 9-12, 2025, San Francisco, California.

Nilu Goonetilleke, LLBHons, BScHons, PhD, presents findings showing the bivalent HIVconsvX vaccine targets both Mosaic-1 and Mosaic-2, resulting in broader immune responses.

Benlarbi M, Finzi A, Durand M, et al. Impact of ART Initiation on HIV-1 Soluble gp120 Levels and CD4 Counts in PWH. Poster #352 presented at CROI 2025. March 9-12, 2025, San Francisco, California.

, held March 9-12, in San Francisco, California, we spoke with three researchers from Université de Montréal about the role of soluble gp120 (sgp120) in people living with HIV (PLWH). Mehdi Benlarbi, a PhD student, explained how sgp120 may contribute to immune dysfunction, even in individuals with undetectable viral loads on ART.

“We believe that soluble gp120, as a viral fragment, can persist in the body even if viral replication is under control with ART,” said Benlarbi. “This persistence leads to chronic inflammation, which may be a factor in the inability of some PLWH to recover their CD4+ T cell counts, despite undetectable viral loads.”

This observation is key to understanding the ongoing challenges faced by PLWH, particularly as they age. “A low CD4 count increases the risk of comorbidities such as cardiovascular disease and cancers,” Benlarbi added. “If we can target sgp120, we may be able to improve immune recovery and reduce the associated risks.”

This research has led to the development of the 

, a clinical trial that is grounded in the work of Mehdi Benlarbi and Professor Andrés Finzi, PhD on sgp120 and fostemsavir. The study aims to explore whether fostemsavir, an investigational therapy, can reduce immune dysfunction and inflammation in PLWH by targeting sgp120. Additionally, it will investigate whether this approach could improve cardiovascular outcomes, given the role of inflammation in the development of cardiovascular disease in PLWH.

Soluble gp120 remains detectable even after ART initiation, suggesting that it may contribute to ongoing immune dysfunction in PLWH. ART suppresses HIV replication effectively, yet many individuals experience immune system impairments, particularly in CD4+ T cell recovery. Preliminary data show a negative correlation between sgp120 levels and CD4+ T cell counts, indicating that sgp120 may impede immune recovery despite viral suppression.

Finzi elaborated on this mechanism, “We view soluble gp120 as a toxin that can engage the CD4 receptor,” said Finzi. “If we could block the ability of gp120 to engage the CD4 receptor, we could neutralize its toxic effect. Fostemsavir, a small molecule inhibitor, can prevent gp120 from binding to CD4, which may alleviate the immune dysfunction caused by this viral protein.”

Fostemsavir has demonstrated in vitro the ability to prevent the interaction between gp120 and CD4, protecting uninfected cells from immune system targeting. This suggests that fostemsavir may help reduce chronic inflammation in PLWH, even with undetectable viral loads.

The RESTART study is a randomized, community-driven clinical trial designed to evaluate fostemsavir’s effects as an add-on therapy to standard ART. Co-designed with a community advisory group of people living with HIV, the study will recruit 150 participants who are 40 years or older, or who have lived with HIV for 25 years or more. All participants will be on ART with undetectable viral loads but detectable sgp120 levels in plasma.

Participants will be randomly allocated to either receive fostemsavir as an add-on to their standard ART regimen or remain on their standard care for two years. The primary goals of the study are to assess the impact of fostemsavir on immune function, inflammation, and cardiovascular health in PLWH.

Madeleine Durand, MD, MSc, associate professor of medicine and a researcher at the CHUM Research Centre, explained the study’s scope, “The research by Andrés and Mehdi gives us hope that targeting residual viral proteins, such as sgp120, could reduce inflammation and immune dysfunction in people living with HIV,” Durand said. “In the RESTART study, we will evaluate whether adding fostemsavir to standard ART can improve immune recovery and reduce the risk of cardiovascular disease.”

Participants will undergo baseline and end-of-study cardiac CT scans to assess whether fostemsavir treatment is associated with a reduction in coronary atherosclerosis, a key indicator of cardiovascular disease. This will provide valuable insights into whether targeting sgp120-associated inflammation can have a beneficial effect on cardiovascular health in PLWH.

At CROI 2025, researchers from Université de Montréal discuss how fostemsavir could target residual viral fragments and reduce inflammation.





Targeting Soluble gp120 to Combat Immune Dysfunction in People Living with HIV

Last week, 20 HIV and hepatitis organizations filed an amicus brief with the Supreme Court in support of the US government’s position in Kennedy v. Braidwood Management, which challenges the Affordable Care Act’s (ACA) preventive services coverage requirement.

The preventative services coverage requires private insurers to include a range of testing, including for HIV and hepatitis B and C, as well as preventative offerings, including PrEP for HIV and vaccinations for hepatitis A and B, and counseling for sexually transmitted infection prevention.

This court case originated in 2023 when 6 Christian-owned businesses in Texas challenged the ACA's preventive services requirement, arguing that the PrEP coverage requirement violated their religious rights.

"Removing access to evidence-based preventive measures will have a devastating impact, not only on those at risk for acquiring HIV and hepatitis but also the population at large,” the HIV and hepatitis organizations wrote in the brief. 

One of the organizations who filed the brief, the HIV+Hepatitis Policy Institute,

“Coverage of no-cost preventive services, including HIV and hepatitis testing, along with PrEP, now rests with the highest court in the land. In our brief, we laid out the critical role testing plays in linking people to life-saving medications and, in the case of hepatitis C, curative treatment, along with the importance of people knowing if they have an infectious disease. We describe the growing importance of PrEP in preventing HIV, including long-acting PrEP drugs, which are almost 100 percent effective in preventing HIV,” Carl Schmid, executive director of the HIV+Hepatitis Policy Institute, said in a statement.

 "We emphasize that coverage of preventive services by private insurers will help end HIV and hepatitis, and losing them would certainly damage the public health of our country and increase medical costs.”

According to HIV.gov, PrEP is highly effective at preventing HIV when taken as indicated. In fact, this form of prevention has been shown to reduce the risk of HIV infection from sex by about 99% when taken as prescribed. And even among people who inject drugs, it reduces the risk by at least 74% when taken as indicated.

Along with the HIV + Hep Policy Institute, the other groups signing on to the brief are: ADAP Advocacy Association, AIDS Alabama, American Academy of HIV Medicine, Caring Ambassadors Program, Community Access National Network, Community Liver Alliance, Community Resource Initiative, Fast Track Cities Institute, Frannie Peabody Center, Georgia AIDS Coalition, Global Liver Institute, Hepatitis B Foundation, Hep B United, Housing Works, International Association of Providers of AIDS Care, Latino Commission on AIDS, NMAC, SIECUS, and Vivent Health.

References
1. 20 HIV & hepatitis organizations urge the U.S. Supreme Court to protect preventive services coverage.HIV and Hep Policy Institute. February 25, 2025. Accessed March 4, 2025.
https://hivhep.org/press-releases/20-hiv-hepatitis-organizations-urge-the-u-s-supreme-court-to-protect-preventive-services-coverage/
2. Preventative Care Benefits for Adults. Healthcare.gov. Accessed March 4, 2025.
 https://www.healthcare.gov/preventive-care-adults/
3. Pre-Exposure Prophylaxis. HIV.gov February 7, 2025. Accessed March 4, 2025.
https://www.hiv.gov/hiv-basics/hiv-prevention/using-hiv-medication-to-reduce-risk/pre-exposure-prophylaxis

Twenty organizations asked the high court to consider the federal government’s position on pre-exposure prophylaxis (PrEP) and HIV and hepatitis testing. 

Joseph Cherabie, MD, MSc

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