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Executive Vice President of Research and Development at Immunocore.

David Berman, MD, PhD, discusses signs of dose-dependent viral control and reduction in active HIV reservoir in Phase 1/2 STRIVE trial data.


Immunocore Reports Some PWH Achieve Viral Control and Dose-Dependent Active HIV Reservoir Reduction in IMC-M113V Trial

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

David Berman, MD, PhD, discusses promising signs of dose-dependent viral control and reduction in active HIV reservoir in Phase 1/2 STRIVE trial data

Title: Immunocore Reports 2/5 Participants Achieve Viral Control and HIV Reservoir Reduction Across 3 Dose Cohorts of IMC-M113V

Immunocore Holdings plc presented early findings from the multiple ascending dose (MAD) phase of its Phase 1/2 STRIVE trial for IMC-M113V at CROI 2025 in San Francisco, California. The data suggest that IMC-M113V, a T-cell receptor bispecific therapy, is well tolerated and demonstrates signs of dose-dependent viral control after antiretroviral treatment (ART) interruption.

The trial included 16 participants living with HIV (PLWH) who were stable on ART. David Berman, MD, PhD, executive vice president of research and development at Immunocore, explained the significance of the study, stating, “Our platform is essentially, we create these off-the-shelf, soluble bispecific proteins, where you have a targeting end to target a specific cell, and then the other end is an effector, which brings T-cells close to the target cell, so close that it actually can kill the target cell. So it acts as a bridge.”

No serious adverse events were observed, and mild cytokine release syndrome (CRS) was noted in some participants at higher doses. The highest dose cohort (300 mcg) showed a dose-dependent increase in T-cell-derived cytokines. “With our cancer programs, we see evidence that you're activating T-cells. So when T-cells get activated, you see cytokines being released in the blood, and that leads to something called cytokine release syndrome. So it's fully expected, and essentially that is typically begins with fever,” Berman explained. “Now with repeated dosing, it doesn't appear to be any other adverse event, so it is very well tolerated.”

Three participants showed delayed viral rebound and subsequent viral control during ART interruption. Viral load in these individuals decreased to approximately 200 copies/mL, a result not commonly seen in untreated PLWH. The trial’s aim is to assess IMC-M113V’s ability to reduce the HIV reservoir and control viral replication after ART interruption. Berman commented, “What we saw, quite remarkably, is a dose-dependent evidence of antiviral reduction, and that's manifest as three of these people living with HIV during the ATI had an increase in their virus initially, and then it seems like the immune system was activated and the virus came under control, and the virus went back down to around 200 copies per million.”

The initial results also show a reduction in CD4+ T-cell-associated HIV Gag RNA in some participants, suggesting a reduction in the active viral reservoir. Berman explained the importance of targeting the viral reservoir, “The viral reservoir, as you point out, was the first measure. And there, it's important to remember that a majority of the viral and the analog I give is the iceberg. If you think of the iceberg, only the tip of the iceberg above the water, the tip of the viral reservoir will actually produce replication competent virus.”

Preliminary data also indicate a trend toward reduced intact HIV DNA in patients treated at the two highest doses. IMC-M113V works by targeting an HLA-A*02:01-Gag complex on HIV-infected cells, using an anti-CD3 effector to recruit T-cells that destroy HIV-infected CD4+ cells. Berman elaborated on how the therapy targets HIV, stating, “We identified a protein in HIV called gag that is chopped up inside the cell, and small peptides are presented on the surface by HLA, and we developed the targeting end of the bispecific to recognize that gag peptide.”

The trial is continuing with higher doses being evaluated, and additional expansion cohorts are planned. Berman emphasized that while the results are promising, further investigation is needed: “We need to continue dose escalating, and then we can, you know, correlate that with clinical outcome.”

The next steps for the treatment involve evaluating the antiviral activity of IMC-M113V in larger cohorts, focusing on correlating the reduction in the viral reservoir with clinical outcomes. Berman noted, “The immediate next steps for us is to continue dose escalating, because if we can, it’s very well tolerated with higher doses, we may even see further reductions. And then we would want to look at correlations between the reservoir reduction and antiviral activity.”

As the trial continues, Immunocore is working to determine whether the antiviral activity can be sustained beyond 12 weeks, with the ultimate goal of achieving a functional cure. “The goal here is functional cure. It's not a 12-week interruption of the treatment,” Berman said. “We wanted to go to the harder population, because you can see a signal. So everyone in our trial started ART later, they're less likely to spontaneously control."

Immunocore Holdings plc. Immunocore presents initial multiple ascending dose data for HIV functional cure candidate in an oral presentation at CROI 2025. 

. March 10, 2025. Accessed March 17, 2025. https://www.immunocore.com/investors/news/press-releases/detail/112/immunocore-presents-initial-multiple-ascending-dose-data-for-hiv-functional-cure-candidate-in-an-oral-presentation-at-croi-2025

Conferences

Colleen Kelley, MD, MPH, offers some insights on where we are today with the state of HIV prevention including  PrEP and PEP, as well as why HIV vaccines are challenging to develop. 

Expanding PrEP Options and the Role of  Broadly Neutralizing Antibodies in Vaccine Development 

Here is the first in a news series on the state of HIV today including prevention, funding, and newer modalities.



HIV prevention in the form of pre-exposure prophylaxis (PrEP) continues to be a highly effective method of reducing the risk of contracting HIV. According to the Centers for Disease Control and Prevention (CDC), PrEP reduces the risk of getting HIV from sex by about 99%, when taken as prescribed.

CDC says there is less information about how effective PrEP pills are among people who inject drugs; however, it is reported that PrEP pills reduce the risk of getting HIV by at least 74% when taken as prescribed. Currently, PrEP injectables are not recommended for people who inject drugs.


One of the more exciting areas within PrEP is long-acting injectables. This modality is giving individuals new options to protect against infection. At this week’s CROI, investigators presented new data on these modalities for FDA approved and developmental PrEP. For example, ViiV Healthcare reported new data the 

long-acting injectable cabotegravir (Apretude) 

demonstrating its effectiveness in 3 years of real-world data. Right now this is the only long-acting injectable that is FDA approved.

Additionally, the investigational long-acting injectable, lenacapavir, has shown high efficacy in phase 3 trials for PrEP and has a PDUFA date for June 19.



Gilead's Once-Yearly Lenacapavir Formulations Show Sustained Efficacy for HIV PrEP in Phase 1 Study



“Long acting injectables are a tremendous advancement, both for HIV prevention and treatment. So with respect to HIV prevention, we know that taking a pill every single day for the duration of the time where you may be exposed to HIV can be difficult for a lot of people,” said Colleen Kelley, MD, MPH, professor, Department of Medicine, Emory University School of Medicine. “We know that about half of people who start oral daily oral PrEP, stop it within the first year of taking it. And so what these long-acting injectables offer is the ability to have excellent HIV prevention without having to think about it, without having to take that pill every single day…and when you take daily oral adherence out of the equation, that's where we see these amazing efficacy results.” 


One area that is not discussed very often is post-exposure prophylaxis (PEP). Kelley says there are 3 challenges around it including the availability of the medication, the duration of the regimen, and potential insurance hurdles.

“It's difficult to access…And they don't know where to get it. They may go to an emergency room, they may go to a clinic, and there's no guarantee that clinic or emergency room will even offer you post exposure prophylaxis in the United States—even though it's recommended,” Kelley said. “And then the second step of how do you get the medication? Does your insurance cover it? Do you need to enroll in a patient assistance program if your insurance doesn't cover it? There's just too many logistical hurdles.”

“The current recommended post exposure prophylaxis regimen is actually 28 days, and that's long for some people who may have had a single exposure to continue taking that medicine every single day for 28 days.”
 

Long acting injectables are a tremendous advancement, both for HIV prevention and treatment. —Colleen Kelley, MD, PhD

Although there are HIV vaccines in development, there are no FDA-approved immunizations. Kelley says the primary challenges to developing such vaccines is the structure of HIV and the ability of the virus to hide away in the body.

“The human immune system makes a very strong antibody response to the SARS-CoV-2 virus, that then helped to attenuated people who had COVID from having severe disease,” Kelley said. That same thing cannot be said of HIV. The HIV antibodies that people get neither prevent them from acquiring HIV, nor prevent them from getting severe disease. And it's because of the structure of the virus, the way that it hides from our immune system, the various ways that it integrates into our cells and just lives there silently. These are all the reasons why we've not been able to create an HIV vaccine similar to the COVID vaccine.”

Although the traditional methodology of creating vaccines has not proven to be efficacious for HIV yet, there is a much newer approach that is starting to be studied for HIV vaccines that includes broadly neutralizing antibodies (bnAbs). The International AIDS Vaccine Initiative (IAVI) has been helping to drive this area of research.

“The origin of our work on a new approach to HIV vaccine design began with the discovery, beginning in 2009, of potent broadly neutralizing antibodies (bnAbs) from large cohorts of individuals living with HIV in Africa, India, Thailand, Australia, the UK, and the US. Researchers at IAVI’s Neutralizing Antibody Center (NAC), a partnership with Scripps Research, and partners isolated and studied these bnAbs, which develop in some people after they have lived with HIV for several years. Later, researchers showed in the lab that some of these bnAbs block HIV from infecting cells,” IAVI writes on its site.

 was reported at this week’s CROI conference by ViiV Healthcare as it relates to HIV management as part of a comprehensive treatment strategy.

The ability to prevent HIV continues to evolve, but it remains to be seen if the significant strides made in HIV prevention will continue, especially in today’s governmental policy environment.




References
1. Let’s Stop HIV Together. CDC. Last reviewed February 18, 2025. Accessed March 13, 2025.
https://www.cdc.gov/stophivtogether/hiv-prevention/prep.html
2. HIV Vaccines. IAVI. Accessed March 13, 2025.
https://www.iavi.org/our-work/hiv-vaccines/

Colleen Kelley, MD, MPH, offers some insights on where we are today with the state of HIV prevention including the expanding PrEP options, why PEP is underutilized, and the challenges behind HIV vaccine development.  

HIV Prevention: Discussing PrEP, PEP, and Vaccine Development

A coalition of employers, the US Business Action to End HIV, sent a letter to Congress outlining the continued need for support from the federal government.

Why it’s Crucial to Maintain Funding for HIV Prevention, Research, Treatment 

This is the second in a series on the state of HIV today.

In late February, The US Business Action to End HIV, the largest coalition of employers dedicated to ending the HIV epidemic in the United States, sent a letter to Congress urging them to prioritize sustained federal funding for HIV prevention and treatment and underscoring the business sector’s commitment to advancing public health and ensuring progress in the fight against HIV.

“We have two goals, one to get people who are living with HIV on treatment, and two, to prevent new acquisition of HIV,” said Carl Schmid, Executive Director, HIV + Hepatitis Policy Institute.

The letter warns that funding freezes and grant delays could threaten hard-won progress, reversing declines in new HIV infections and exacerbating health disparities. Business leaders are calling on Congress to maintain investments in HIV research, prevention, and access to care, emphasizing that ending the epidemic is both a moral and economic imperative.

More specifically, the Coalition urges Congress to:

Maintain federal funding and state HIV prevention and treatment programs to safeguard decades of hard-won progress

Advance policies that sustain and expand life-saving public health efforts to keep the momentum going

Expand access to essential HIV services like testing, prevention, and treatment so everyone can stay healthy - regardless of where they live or their circumstances. (HIV continues to affect some communities more than others, particularly in parts of the US South, where access to prevention and care remains a challenge)

Strengthen public-private collaboration to close gaps in care, especially in communities most impacted by HIV.

“We saw a pretty steady decrease in the number of new HIV infections in this country between 2018 and 2022 but this progress is fragile, and reductions in funding or rollbacks and policy efforts could really risk a resurgence in new HIV infections and in preventable deaths, which would undermine all of the hard won gains that we've made,” said Stephen Massey, co-founder and co-CEO of the US Business Action to End HIV.

In terms of the business sector and their role in addressing these issues, Massey says companies have an opportunity to create a comfortable environment, to be able to have employers communicate with their employees about HIV, as well as what types of health plans they offer.

“There is an opportunity for employers to share trusted information about HIV, including how to prevent infection. There's an opportunity for employers to create workplaces where employees feel comfortable talking about HIV, asking questions, and also workplaces where employees have access to the very best care and prevention,” Massey said. “Employers play a really important role in determining health care plans that employees are offered for employees who might not be covered by their insurer. They could also provide information to employees about how they can access the social safety net of services that are available.”

“The community can advocate for ourselves, but I think it's really helpful, particularly in this time period, to have additional voices, including those of the business community,” Schmid said. “They can go into congressional offices and places where perhaps the community doesn't have the same footing.”

The Business Sector's Advocacy to Maintain Funding for HIV Prevention, Research, Treatment 

New pharmacokinetic data from CROI 2025, shared by Moupali Das, reveal long-lasting plasma concentrations, surpassing twice-yearly subcutaneous formulation for HIV prevention

Once-Yearly Lenacapavir Formulations Show Sustained Efficacy for HIV PrEP in Phase 1 Study

At the CROI 2025, Moupali Das, MD, MPH, vice president of HIV prevention and virology pediatrics at Gilead Sciences, discussed new findings from a Phase 1 study investigating two formulations of once-yearly intramuscular (IM) lenacapavir for HIV pre-exposure prophylaxis (PrEP). These results, published simultaneously in 

, present significant progress in the fight against HIV and could pave the way for a new class of long-acting prevention options.

Comparing Once-Yearly and Twice-Yearly Formulations of Lenacapavir

In the Phase 1 study, participants received a single dose of 5000 mg of either formulation 1 (with 5% ethanol) or formulation 2 (with 10% ethanol), administered via intramuscular injection. Both formulations demonstrated promising pharmacokinetic profiles, with concentrations of lenacapavir maintained at levels above the threshold associated with efficacy for over 56 weeks.

Das explained, “The bottom line is, the formulations compare quite well. The pharmacokinetics data show that these once-yearly formulations of lenacapavir last longer than 52 weeks—specifically, 56 weeks—and remain above the 95% effective concentration.”

Key results from the study included median trough concentrations at Week 52 of 57 ng/mL (for formulation 1) and 65.6 ng/mL (for formulation 2), both of which surpassed the median trough concentration observed in the twice-yearly subcutaneous (SC) formulation (23.4 ng/mL at Week 26 from previous PURPOSE trials). These results highlight that the once-yearly formulations not only last longer but also maintain higher plasma concentrations compared to the twice-yearly SC formulation.

The study confirmed that these high concentrations were sustained throughout the 56-week period. The median peak plasma concentration for formulation 1 was 247 ng/mL while formulation 2 had a higher peak at 336 ng/mL, which remained well above the highest concentration observed for the twice-yearly SC formulation (67.3 ng/mL).

Injection Site Reactions and Safety Profile

As with many injectables, injection site reactions are a key consideration in any clinical trial. In this study, the most common adverse event reported was injection-site pain, a result consistent with what has been seen with other long-acting injectable formulations. According to Das, “The most common side effect was injection-site pain, which is not surprising. In our study, 80% of people receiving formulation 1 and 75% with formulation 2 reported some pain at the injection site. It was mostly mild to moderate and resolved within a few days.”

Das also noted that pre-treatment with ice, a strategy proven useful in earlier studies with the twice-yearly SC formulation, helped reduce the pain associated with the injections. “Pre-treatment with ice, as we used in the PURPOSE trials, was effective in reducing injection-site pain, and we continued that in this study.”

The safety profile of the once-yearly formulations was consistent with what has been observed in prior lenacapavir studies. No severe adverse events or abnormal lab findings were reported, indicating that both formulations of lenacapavir were well tolerated.

Given the encouraging data from the Phase 1 study, Das outlined the next steps in the development of once-yearly lenacapavir for HIV PrEP. “We’re continuing to monitor plasma concentrations and safety, and we plan to initiate a Phase 3 trial later this year to determine which formulation we will pursue for further development,” Das explained. “These findings are very promising, and we are hopeful that once-yearly lenacapavir will eventually become a viable option for HIV prevention.”

Das emphasized that lenacapavir’s flexibility—offering potential formulations in daily oral, weekly oral, and long-acting injectable forms—could help address a variety of patient needs. “Lenacapavir is a unique molecule with multiple ways to be used in HIV prevention, from oral tablets to long-acting injectables,” she said. “We’re particularly excited by the potential of the once-yearly injectable, as it could address adherence challenges many individuals face with daily regimens or more frequent injectable options.”

“Many people face challenges when it comes to daily pills or even something more frequent like monthly injections,” Das said. “We’re hopeful that if the once-yearly formulation is approved, it will improve adherence, help people stay on PrEP, and ultimately reduce new HIV infections globally.”

The Phase 1, open-label study included 40 healthy adult participants aged 18-55 years. Participants were divided into two groups, with one group receiving formulation 1 (5% ethanol) and the other receiving formulation 2 (10% ethanol). The study followed participants for up to 56 weeks, measuring plasma concentrations of lenacapavir at multiple time points, from baseline to Week 56. The pharmacokinetic parameters assessed included the area under the concentration-time curve (AUC), peak plasma concentration, and trough concentration (Ctrough).

The study's results were compared to data from the PURPOSE 1 and PURPOSE 2 Phase 3 trials, which evaluated twice-yearly subcutaneous lenacapavir for HIV prevention. As noted, the once-yearly IM formulations not only sustained higher concentrations for a longer period but also demonstrated safety and tolerability profiles in line with previous findings.

Gilead Sciences, Inc. First Clinical Data for Gilead’s Investigational Once-Yearly Lenacapavir for HIV Prevention Presented at CROI 2025 and Published in 

. March 11, 2025. Accessed March 11, 2025. 

https://www.gilead.com/news/news-details/2025/first-clinical-data-for-gileads-investigational-once-yearly-lenacapavir-for-hiv-prevention-presented-at-croi-2025-and-published-in-the-lancet

Jogiraju V, Pawar P, Yager J, et al. Pharmacokinetics and safety of once-yearly lenacapavir: a phase 1, open-label study. 

. Published March 11, 2025. doi: 10.1016/S0140-6736(25)00405-2

New pharmacokinetic data, shared by Moupali Das, MD, MPH, reveal long-lasting plasma concentrations, surpassing twice-yearly subcutaneous formulation for HIV prevention

Gilead's Once Yearly Lenacapavir Formulations Show Sustained Efficacy for HIV PrEP in Phase 1 Study

Investigators found they could reduce the once-daily (OD) dosing of bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF; Biktarvy; Gilead) from OD up to 3 weeks safely and effectively over a nearly a year time period.

“In virally suppressed [people with HIV] on [BIC/FTC/TAF] BETAF OD, the strategy of reducing the BETAF OD dose to 3W, 2W, or 1W for 48 weeks was safe, well tolerated, and effective as compared with continuing OD,” the investigators wrote.

 The findings were presented as a poster at 

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

BIC/FTC/TAF in the small pilot study encompassed 40 participants with well-controlled HIV. Individuals were randomized (n = 10 per arm) to: OD, 3W (Mon-Wed-Fri), 2W (Tue-Fri), or 1W (Wed) with visits at baseline and 4, 12, 24, 36, and 48 weeks.

The investigators had strict criteria for dissolution of both the arms and individual participants.

“Individuals with viral failure (confirmed VL ≥50 c/mL) underwent genotypic resistance testing and were switched to OD up to 48 weeks,” the investigators wrote. “We measured ultrasensitive VL; total, defective, and intact HIV reservoir (IPDA); CD4 and CD8 cells; hsCRP and IL-6; and plasma and intracellular trough drug levels at baseline, 12, and 48 weeks. The stopping rule was >30% viral failure in any of the dose reduction arms.”

In terms of viral rebound, 3 participants experienced the phenomenon, with 2 of them coming from the 1-week cohort and 1 coming from the 3-week cohort. The investigators reported no resistance mutations developed, and viral suppression was restored after they went back to OD dosing.

"There were no significant differences in ultrasensitive VL, HIV reservoir, CD4 or CD8 cells, and hsCRP or IL-6 among arms. Although trough plasma and intracellular drug levels significantly decreased in 3W, 2W, and 1W relative to OD at 12 and 48 weeks, mean trough levels at 12 and 48 weeks in 3W and 2W, but not in 1W, were generally above the known inhibitory concentrations," the investigators wrote.

FDA approved the Gilead ART back in February 2018. At the time of the approval, the company said the following in its press release: “Biktarvy combines the novel, unboosted integrase strand transfer inhibitor (INSTI) bictegravir, with the demonstrated safety and efficacy profile of the Descovy (FTC/TAF) dual nucleoside reverse transcriptase inhibitor backbone, and is the smallest INSTI-based triple-therapy STR available.”

1. Chivite I, et al. Safety, Tolerability, and Efficacy of a BIC/FTC/TAF Dose Reduction Strategy. Poster #659 presented at CROI 2025. March 9-12, 2025, San Francisco, California.
2. Rosa K.FDA Approves Bictegravir for HIV-1. 

February 7, 2018. https://www.contagionlive.com/view/fda-approves-bictegravir-for-hiv



In a small study, investigators found they could reduce the antiretroviral therapy (ART) dosing to longer durations and the treatment remained safe and efficacious.

David Berman, MD, PhD

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