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Schmalzle is an infectious disease physician, and medical director of the THRIVE Program HIV clinic at the University of Maryland. She leads a multidisciplinary team in piloting the STRONG and STRIVE to 100 HIV-aging models of care.

As the cohort of people living with HIV in the US ages, HIV care programs must rapidly adapt to the changing needs of older adults with HIV. 

HIV's Golden Age: Responding to the Needs of an Aging Population

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

SHIELD Study Finds Novavax Recipients Missed Less Work and Reported Lower Reactogenicity Than Pfizer-BioNTech Recipients

Novavax COVID-19 Vaccine Linked to Fewer Side Effects in Health Care Workers and First Responders

In a real-world study of frontline health care workers (HCWs) and first responders (FRs) in the United States, recipients of the updated 2024–2025 Novavax (NVX) COVID-19 vaccine reported fewer and less severe side effects than those who received the updated Pfizer-BioNTech (PFZ) mRNA vaccine. These findings suggest the Novavax vaccine may cause less disruption to work and daily life activities.

The prospective SHIELD study, presented at ESCMID and conducted at the University of Utah between September and December 2024, specifically targeted HCWs and FRs, a critical population for pandemic response. Among 588 participants (mean age 36.4 years, 70.1% female), NVX recipients reported significantly fewer systemic reactogenicity events within 48 hours post-vaccination compared to PFZ recipients (73.6% vs. 87.5%). NVX recipients also experienced fewer systemic symptoms on average (1.7 vs. 2.8) and were less likely to have symptoms rated as moderate or severe (19.2% vs. 44.5%).

Matthew Rousculp, vice president at Novavax, explained the motivation behind the study, "The intent of the study was really to try to understand, is there a difference in reactogenicity, or really what we talk about these mild side effects that occur after being vaccinated between COVID-19 vaccines."

Importantly, the study also measured how adverse events impacted participants’ ability to work and engage in daily activities. NVX recipients missed fewer hours of work or daily tasks (0.7 hours vs. 1.4 hours for PFZ recipients) and reported fewer hours of reduced productivity (0.8 hours vs. 2.4 hours).

Using the Sheehan Disability Index, researchers found that 54.3% of NVX recipients reported no impact on work or school activities, compared to 39.3% of PFZ recipients. Similarly, 72.6% of NVX recipients reported no impact on social or leisure activities, versus 57.5% among PFZ recipients.

Rousculp emphasized that the study was designed with clinicians in mind, "Really at the end of the day, it's a study that was predominantly 20% physicians, 20% nurse practitioners or nurses. 83% percent worked in hospitals. So these results are really relevant for the practicing clinician."

He noted that health care workers are often key sources of information for vaccine-hesitant patients, making their personal experiences particularly influential, "We know that healthcare workers are the prime source of information for individuals who have a form of hesitancy... really being able to talk with some authoritarian perceptions is very vital."

The SHIELD study assessed four dimensions of reactogenicity: the presence of systemic and local symptoms (such as fever or injection site pain), the number of simultaneous adverse events, severity graded as moderate or severe (Grade 2 or 3), and the impact on daily activities.

"We just want to say the percent who experienced [symptoms], how many of those adverse events did you experience at the same time, how severe they were, and whether it impacted work, family time, or leisure events," Rousculp explained.

While acknowledging the limitations of observational studies, such as potential self-reporting bias, the SHIELD findings reinforce earlier data suggesting that protein-based COVID-19 vaccines like Novavax's may be associated with lower burdens of side effects compared to mRNA vaccines.

Ultimately, Rousculp emphasized that these findings are intended to empower both clinicians and patients in shared decision-making about vaccination choices, "With that information, it's really going to be very much at the physician level, as well as the patient level, to really kind of make the decision as far as what might be the best option."

 has requested that Novavax conduct an additional clinical trial for its updated COVID-19 vaccine, NVX-CoV2601, delaying its full approval beyond the original April 1, 2025, deadline. Despite earlier optimism from Novavax that its Biologics License Application was approvable, intervention by new Department of Health and Human Services leadership and concerns over the vaccine’s composition led to the request for new data. Interim results from a phase 2/3 study showed that NVX-CoV2601, targeting the Omicron XBB.1.5 variant, produced significantly higher neutralizing antibody responses and maintained a manageable safety profile, supporting its potential as an effective booster. Novavax remains in negotiations with the FDA regarding the size and scope of the new trial.

1. Rousculp MD, Phillips AL, Ellsworth GL, et al. 

Impact of Reactogenicity of the 2024-2025 COVID-19 Vaccines on Health Care Workers and First Responders in the United States.

 Presented at: ESCMID 2025 Annual Meeting; April 2025; Vienna.

2. US FDA asks Novavax to complete new clinical trial for delayed COVID-19 shot, WSJ reports. News release. Reuters. April 25, 2025. Accessed April 28, 2025. https://www.reuters.com/business/healthcare-pharmaceuticals/fda-asks-novavax-complete-new-clinical-trial-delayed-covid-19-shot-wsj-reports-2025-04-25/

At ESCMID Global 2025, SHIELD study data show Novavax recipients experienced fewer adverse effects and missed less work compared with those who received the Pfizer-BioNTech COVID-19 vaccine.


Conferences

Novavax COVID-19 Vaccine Linked to Fewer Adverse Effects in Health Care Workers and First Responders

In a real-world US study of frontline health care workers (HCWs) and first responders (FRs), the updated 2024–2025 Novavax (NVX) COVID-19 vaccine was associated with fewer and milder side effects compared to the updated Pfizer-BioNTech (PFZ) mRNA vaccine. The findings, presented at the ESCMID Global Congress 2025, suggest the Novavax vaccine may cause less disruption to work and daily life. The prospective SHIELD study, conducted at the University of Utah, enrolled 588 participants between September and December 2024 (mean age 36.4 years; 70.1% female). Compared to PFZ recipients, those who received the NVX vaccine reported significantly fewer systemic side effects within 48 hours post-vaccination (73.6% vs 87.5%), fewer symptoms on average (1.7 vs 2.8), and were less likely to experience moderate or severe symptoms (19.2% vs 44.5%). In the nect part of his interview with Contagion, Matthew Rousculp, vice president at Novavax, provided additional context behind the study findings. "So there's two components to that," Rousculp said. "So for us, as far as biases, what we want to do is after capturing the data, because again, it's observational, it's not a randomized study. So a prospective observational study, we do have the ability to use statistical diagnostics to go look to say, look, is there a difference between two groups, those who had received the Novavax vaccine versus those who received the mRNA or the Pfizer-BioNTech vaccine? And then also there are methods where you can actually try to control for this." Rousculp emphasized that while the study was not randomized, the populations were largely comparable at baseline, "We really, really worked hard. What we really saw were that the populations were very, very similar," he explained. "Really didn't see reasons why they were choosing it except for they came in, offered it, and it was just their choice at that time." Some potential biases, such as participants’ prior experiences with COVID-19 vaccines influencing their selection, could not be fully accounted for, he acknowledged, "We weren't able to control, for example, people's previous experience on the vaccine. Did that impact what vaccine they actually selected? So that we weren't able necessarily to capture," Rousculp said. "But we do see that the results are very consistent with... all those previous studies." The SHIELD study focused on several dimensions of reactogenicity: incidence, average number of symptoms, severity of symptoms, and impact on daily activities, "The results that came out of the study really were all about trying to understand how burdensome, how bothersome vaccine reactogenicity were for those who had received the COVID-19 vaccine, either the Novavax vaccine or the mRNA vaccine," Rousculp explained. "And so the way we measured that was really those four dimensions." He continued, "What we saw is there was significant difference in all four of those dimensions. And we saw that the Novavax vaccine was less burdensome than the mRNAs. Again, that's very consistent with previous studies." Rousculp also pointed to the broader issue of vaccine hesitancy, noting that COVID-19 vaccination rates remain low, particularly among high-risk groups, "We have seen vaccine percentage rates for COVID-19, or what CDC has really reported for this current season, that high-risk populations, for example, 65 years and older, as of this season, only about 30% have been vaccinated with COVID-19 vaccines," he said. "So there's this really big drawback of wanting to be vaccinated." He emphasized that side effects associated with Novavax's COVID-19 vaccine appear comparable to those seen with high-dose influenza or pneumococcal vaccines, "So how does this reactogenicity of the Novavax vaccine actually compare to other vaccines? There have been some other studies that look at this," he said. "And so really what's being reported is that reactogenicity for the Novavax vaccine is clinically similar to those that receive a high-dose flu vaccine or receive a pneumococcal vaccine." Ultimately, Rousculp stressed the importance of empowering individuals with data-driven insights to support informed decision-making, "I feel as if for us is that individuals, as they get more information, are able to really kind of make the decisions based upon facts and information that they know are based in research," he said. "And suddenly going about testing, that they can have a very honest conversation with their health care providers, with their family, with their friends."  Reference Rousculp MD, Phillips AL, Ellsworth GL, et al. Impact of Reactogenicity of the 2024-2025 COVID-19 Vaccines on Health Care Workers and First Responders in the United States. Presented at: ESCMID 2025 Annual Meeting; April 2025; Vienna.

Matthew Rousculp, Vice President at Novavax, explained the motivation behind the study:

In a real-world US study of frontline health care workers (HCWs) and first responders (FRs), the updated 2024–2025 

 (NVX) COVID-19 vaccine was associated with fewer and milder side effects compared to the updated Pfizer-BioNTech (PFZ) mRNA vaccine. The findings, presented at the ESCMID Global Congress 2025, suggest the Novavax vaccine may cause less disruption to work and daily life.

The prospective SHIELD study, conducted at the University of Utah, enrolled 588 participants between September and December 2024 (mean age 36.4 years; 70.1% female). Compared to PFZ recipients, those who received the NVX vaccine reported significantly fewer systemic side effects within 48 hours post-vaccination (73.6% vs 87.5%), fewer symptoms on average (1.7 vs 2.8), and were less likely to experience moderate or severe symptoms (19.2% vs 44.5%).

, Matthew Rousculp, vice president at Novavax, provided additional context behind the study findings.

"So there's two components to that," Rousculp said. "So for us, as far as biases, what we want to do is after capturing the data, because again, it's observational, it's not a randomized study. So a prospective observational study, we do have the ability to use statistical diagnostics to go look to say, look, is there a difference between two groups, those who had received the Novavax vaccine versus those who received the mRNA or the Pfizer-BioNTech vaccine? And then also there are methods where you can actually try to control for this."

Rousculp emphasized that while the study was not randomized, the populations were largely comparable at baseline, "We really, really worked hard. What we really saw were that the populations were very, very similar," he explained. "Really didn't see reasons why they were choosing it except for they came in, offered it, and it was just their choice at that time."

Some potential biases, such as participants’ prior experiences with COVID-19 vaccines influencing their selection, could not be fully accounted for, he acknowledged, "We weren't able to control, for example, people's previous experience on the vaccine. Did that impact what vaccine they actually selected? So that we weren't able necessarily to capture," Rousculp said. "But we do see that the results are very consistent with... all those previous studies."

The SHIELD study focused on several dimensions of reactogenicity: incidence, average number of symptoms, severity of symptoms, and impact on daily activities, "The results that came out of the study really were all about trying to understand how burdensome, how bothersome vaccine reactogenicity were for those who had received the COVID-19 vaccine, either the Novavax vaccine or the mRNA vaccine," Rousculp explained. "And so the way we measured that was really those four dimensions."

He continued, "What we saw is there was significant difference in all four of those dimensions. And we saw that the Novavax vaccine was less burdensome than the mRNAs. Again, that's very consistent with previous studies."

Rousculp also pointed to the broader issue of vaccine hesitancy, noting that COVID-19 vaccination rates remain low, particularly among high-risk groups, "We have seen vaccine percentage rates for COVID-19, or what CDC has really reported for this current season, that high-risk populations, for example, 65 years and older, as of this season, only about 30% have been vaccinated with COVID-19 vaccines," he said. "So there's this really big drawback of wanting to be vaccinated."

He emphasized that side effects associated with Novavax's COVID-19 vaccine appear comparable to those seen with high-dose influenza or pneumococcal vaccines, "So how does this reactogenicity of the Novavax vaccine actually compare to other vaccines? There have been some other studies that look at this," he said. "And so really what's being reported is that reactogenicity for the Novavax vaccine is clinically similar to those that receive a high-dose flu vaccine or receive a pneumococcal vaccine."

Ultimately, Rousculp stressed the importance of empowering individuals with data-driven insights to support informed decision-making, "I feel as if for us is that individuals, as they get more information, are able to really kind of make the decisions based upon facts and information that they know are based in research," he said. "And suddenly going about testing, that they can have a very honest conversation with their health care providers, with their family, with their friends."

Rousculp MD, Phillips AL, Ellsworth GL, et al. 

Novavax Vice President Matthew Rousculp on reactogenicity, vaccine hesitancy, and supporting informed decisions.

Novavax vs mRNA Vaccines: Understanding Vaccine Reactogenicity

The therapy, lenacapavir, showed sustained virological suppression and safety over a 2-year period in this treatment-challenged patient population. 

Examining a Newer Combination Therapy for Heavily Treated HIV Patients

People with multi-drug resistant (MDR) HIV have limited antiretroviral therapy (ART) options, which can leave their disease management very challenging.

“The patients who meet this definition tend to be very well known to us,” Onyema Ogbuagu, MBBCh, FACP, FIDSA, director of HIV Clinical Trials program at Yale School of Medicine, said. “I provide HIV care, and we all know many of these patients tend to be people who have long [been] in HIV care—it is typically not the newly infected.”

He says that these patients may have been diagnosed with HIV as children and now are adults or maybe they are older adults who had HIV for decades, and their ART regimens are less effective in keeping their HIV viral loads suppressed.

“Someone gave a talk today at CROI, [and the person] said that people don't fail drugs, but drugs fail people,” Ogbuagu said.

It is within this context, that treatment for these patients with multidrug resistance need an additional therapy to keep their viral loads down and prevent them from becoming vulnerable to other opportunistic infections.

There is a newer therapy, lenacapavir (Sunlenca), which has shown some promising data in addressing MDR HIV and as a potential complement to existing ART regimen in these aforementioned patients. Lenacapavir is a first-in-class, investigational long-acting HIV capsid that was 

 in late 2022 and is indicated for adult patients living with HIV, whose infections cannot be successfully treated with other available treatments due to resistance, intolerance, or safety consideration.

Lenacapavir is manufactured by Gilead, and at this week’s 

Conference on Retroviruses and Opportunistic Infections (CROI)

 in Denver, CO, new data was presented that demonstrated treatment benefits over a 2-year periodfrom the phase 2/3 CAPELLA trial evaluating the lenacapavir. Ogbuagu was at CROI, and is a principal investigator on the trial. 

CAPELLA is a double-blinded, placebo-controlled global multicenter study designed to evaluate the antiviral activity of lenacapavir when administered every 6 months as a subcutaneous injection in heavily treatment-experienced (HTE) people with MDR HIV infection. The eligible participants had resistance to ≥2 ARVs in ≥3 of the 4 main ARV classes (NRTI, NNRTI, PI, INSTI).

The optimized background regimen (OBR) participants were selected by individual clinicians, and other investigational drugs were permitted for the study.

The investigators wrote that the OBR overall susceptibility score was the sum of susceptibility scores for each OBR ARV; 0 (no susceptibility), 0.5 (partial susceptibility) and 1 (full susceptibility) and efficacy was assessed at Weeks 26, 52, and 104. Lenacapavir and OBR ARV resistance analyses were done at virologic failure (virologic rebound ≥50 copies/mL or <1 log10 decline vs baseline).

There were 72 patients enrolled, and of them, 12 (17%) had no fully active antiretrovirals in their OBR; 6 of 12 and 1 of 12 had 1 or 2 partially active (score 0.5 each) ARVs, respectively. The investigators report the median (range) number of OBR ARVs was 4 (2–6). Overall, OBR comprised NRTI (9 participants), INSTI (8), PI (7) or NNRTI (6); 5, 2, and 2 participants were on a CD4 post-attachment inhibitor (ibalizumab), CCR5 inhibitor (maraviroc), or attachment inhibitor (fostemsavir), respectively.

The trial was conducted over a 2-year period, and Ogbuagu says this was about looking at the modality of subcutaneous injections as it related to safety, but also the long-term efficacy of the therapy.

“We found even as far out as two years or the so called 104 [week] data, that about 82% of individuals—when we excluded those who are missing— were virologically suppressed…that's unheard of numbers for this kind of patient population,” Ogbuagu said. “We have other studies with other agents that have shown lower rates of treatment success with these kinds of patients.”

spoke to Ogbuagu during CROI about lenacapavir's mechanism of action, more insights around the CAPELLA study, and the value he sees in the addition of this HIV therapy.

Ogbuagu O, Ratanasuwan W, Avihingsanon A, et al. Lenacapavir Efficacy IN CAPELLA Patients With No Fully Active Agents In Optimized Background Regimen. Poster #630 presented at CROI 2024. March 3-6, 2023. Denver, CO.

Examining a Newer Therapy for Heavily Treated HIV Patients

Gilead announced today that its twice-yearly injectable HIV capsid inhibitor, lenacapavir (Sunlenca), was more efficacious in preventing HIV infection than a daily PrEP pill, emtricitabine and tenofovir disoproxil (Truvada).

Early data was shared from the PURPOSE 2 phase 3 clinical trial. The investigators reported there were 2 confirmed cases of HIV among 2,180 participants in the lenacapavir group (incidence 0.10 per 100 person-years); thus demonstrating a 99.9% prevention rate amongst participants. The results demonstrated superiority of twice-yearly lenacapavir over bHIV (incidence 2.37 per 100 person-years), with 96% relative risk reduction (incidence rate ratio 0.04, p<0.0001). 

There were 9 incident cases among 1,087 individuals in the Truvada group (incidence 0.93 per 100 person-years). Twice-yearly lenacapavir was 89% more effective than once-daily Truvada (incidence rate ratio 0.11, p=0.00245).

“The incredible efficacy demonstrated in the PURPOSE 2 trial, the potential benefits of a twice-yearly injection, and the diversity of trial sites and participants show the impact that lenacapavir for PrEP could have for people around the world who need new choices to reduce their chances of acquiring HIV. This breakthrough adds significantly to our arsenal of tools to move us closer to achieving an AIDS-free generation,” said PURPOSE 2 principal investigator Onyema Ogbuagu, MBBCh, FACP, FIDSA, associate professor of Medicine and Pharmacology at Yale School of Medicine and director of the Yale Antivirals and Vaccines Research Program.


The second trial, PURPOSE 2, includes cisgender men, transgender men, transgender women, and gender non-binary individuals in Argentina, Brazil, Mexico, Peru, South Africa, Thailand and the United States who have sex with partners assigned male at birth. At interim analysis, the independent Data Monitoring Committee (DMC) confirmed that the PURPOSE 2 trial met its key efficacy endpoints of superiority of twice-yearly lenacapavir to both bHIV (primary endpoint) and once-daily oral Truvada (secondary endpoint) for pre-exposure prophylaxis (PrEP). Therefore, the DMC recommended that Gilead stop the blinded phase of the trial and offer open-label lenacapavir to all participants.

Study participants were randomized in a 2:1 ratio to lenacapavir and Truvada, respectively. Because effective PrEP options already exist, there is broad consensus in the PrEP field that a placebo group would be unethical; thus, the trial used bHIV as the primary comparator and Truvada as a secondary comparator.

Both lenacapavir and Truvada were generally well-tolerated and no significant or new safety concerns were identified.

This is the second phase 3 trial to demonstrate superior efficacy for twice-yearly lenacapavir for the investigational use of HIV prevention as PrEP. In June 2024, the first study, aptly named, PURPOSE 1 trial, which studied lenacapavir for PrEP among cisgender women in sub-Saharan Africa, demonstrated 

 in preventing HIV infection among participants. The trial encompassed over 5,300 participants across South Africa and Uganda.



“With such remarkable outcomes across 2 phase 3 studies, lenacapavir has demonstrated the potential to transform the prevention of HIV and help to end the epidemic,” said Gilead CEO Daniel O'Day in a statement.

 to lenacapavir was brought up during the International AIDS Society 2024 conference in July, especially in areas of need and those low and middle income countries.

In today’s press statement, the company looked to address that.

“Gilead is executing an access strategy that prioritizes speed and enables the most efficient paths for the regulatory review and approval of lenacapavir for PrEP in regions around the world. This strategy will prioritize high-incidence, low-resource countries, which are primarily low- and lower-middle income countries. Gilead is committed to making lenacapavir available in the countries where the need is greatest, including expediting voluntary licensing partners to supply high-quality, low-cost versions of lenacapavir. Gilead is actively working to finalize these contracts.”

Gilead said it plans to continue its pursuit of regulatory approvals. “Now that we have a comprehensive dataset across multiple study populations, Gilead will work urgently with regulatory, government, public health and community partners to ensure that, if approved, we can deliver twice-yearly lenacapavir for PrEP worldwide, for all those who want or need PrEP,” said O’Day.

References
1. Gilead’s Twice-Yearly Lenacapavir for HIV Prevention Reduced HIV Infections by 96% and Demonstrated Superiority to Daily Truvada® in Second Pivotal Phase 3 Trial. Gilead press release. September 12, 2024. Accessed September 12, 2024.


https://www.gilead.com/news-and-press/press-room/press-releases/2024/9/gileads-twiceyearly-lenacapavir-for-hiv-prevention-reduced-hiv-infections-by-96-and-demonstrated-superiority-to-daily-truvada-in-second-pivotal-ph

2. Press Release. Gilead’s Twice-Yearly Lenacapavir Demonstrated 100% Efficacy and Superiority to Daily Truvada® for HIV Prevention. 

Published June 20, 2024. Accessed June 20, 2024. 

https://www.gilead.com/news-and-press/press-room/press-releases/2024/6/gileads-twiceyearly-lenacapavir-demonstrated-100-efficacy-and-superiority-to-daily-truvada-for-hiv-prevention

Gilead’s HIV-1 capsid inhibitor, which is a twice-yearly injection, was more effective than a daily Truvada pill in a phase 3 trial. 

Lenacapavir Reduces HIV Infections by 96%, Demonstrates Superiority Over Another HIV Prophylactic

A recent study presented at IDWeek by Onyema Ogbuagu, MD, associate professor of medicine and pharmacology at Yale School of Medicine, highlights the efficacy of long-acting subcutaneous lenacapavir (LEN) for treating multidrug-resistant HIV-1 in heavily treatment-experienced (HTE) individuals. Over a three-year period, the CAPELLA study demonstrated significant virologic suppression and a favorable safety profile for this first-in-class capsid inhibitor.

At the conclusion of the CAPELLA study, 61% of participants achieved HIV-1 RNA levels below 50 copies/mL. This figure increased to 84% when excluding individuals with missing data. Notably, 88% of those receiving LEN achieved a half-log reduction in viral load, compared to only 17% on placebo.

In our exclusive interview with Ogbuagu, he stated, “We're excited to present the three-year results from the CAPELLA study, which looked at lenacapavir. This is an exciting compound because it's a first-in-class novel capsid inhibitor for HIV treatment, studying it in patients for whom there is an identified need.” He emphasized the unique position of this therapy in addressing the complex challenges faced by HTE patients, who have often exhausted available treatment options.

The study enrolled 72 participants, with a median age of 52 years. Among them, 64% had a CD4 cell count below 200 cells/μL. By Week 156, the median increase in CD4 cell count was 115 cells/μL, indicating improved immune function among participants. Ogbuagu remarked on the significance of these findings: “These are really amazing numbers for a very hard-to-treat population. Our study showed that even as far out as three years, the injection was safe and well tolerated.” Participants received LEN oral initiation followed by subcutaneous (SC) LEN every 6 months combined with an OBR.

In terms of safety, injection site reactions (ISRs) were primarily mild, with most reactions categorized as Grade 1 or 2. Dr. Ogbuagu underscored the importance of thoroughly assessing the safety profile of LEN, saying, “One of the new categories of adverse events we consider with parenterally administered compounds like lenacapavir is injection site reactions, which we don't worry about with oral therapies.” He noted that while ISRs were common, the vast majority of cases were manageable and typically resolved quickly.

“The good news is that, in general, even though the vast majority of participants did have some form of injection site reactions, they tended to be mild—typically Grade 1, with occasional Grade 2 reactions,” he explained. He also acknowledged that some nodules and induration could persist between injections, yet added a reassuring note: “Despite the proportion of individuals who reported these reactions, people tend to tolerate them safely. Additionally, we find that over time, individuals get used to the injections and report fewer adverse events as time goes on.”

Antimicrobial resistance to LEN was noted in 14 participants, primarily linked to poor adherence to their optimized background therapy. Ogbuagu discussed the need for careful management of these patients to avoid resistance development. “If we backtrack, we remember that many of the patients we included in the study had very high rates of resistance to antiretroviral drugs,” he stated. “Almost half had resistance to two or more drugs in all four main classes of antiretroviral drugs.”

He emphasized the importance of supporting adherence to the optimized background regimen, noting, “The vast majority of those who developed resistance were individuals who were poorly adherent.” His advice for clinicians is clear: “You really want to use lenacapavir in combination with at least one additional fully active agent where possible to mitigate the risk of emergent resistance.”

The results of the CAPELLA study have important implications for future treatment guidelines for HTE individuals with MDR HIV. “Lenacapavir is just a welcome addition to the repertoire of drugs for multi-drug resistant HIV,” Ogbuagu said. He highlighted the advantages of LEN as an injectable treatment that can be administered in a clinical setting: “Inherently, due to its mechanism of action and the way it's administered, we can support adherence for individuals because we give the injections in the clinic. This allows us to remind people of their appointments and keep track of their treatment history.”

Overall, the findings from the CAPELLA study reaffirm the efficacy and safety of LEN as a treatment option for HTE individuals with multidrug-resistant HIV. The long-term data support LEN’s role in achieving sustained virologic suppression, highlighting its potential as a critical component of HIV treatment regimens for patients with limited options.

With the integration of LEN into clinical practice, healthcare providers can enhance adherence and improve treatment outcomes for this challenging patient population. Ogbuagu’s insights underscore ongoing support and management to maximize the benefits of this innovative therapy in the fight against HIV.

Ogbuagu O, et. al. Long-Acting Subcutaneous Lenacapavir in People with Multi-Drug Resistant HIV-1: 3-Year Results of the CAPELLA Study. Presentation #155 presented at IDWeek 2024. October 16-19, 2024. Los Angeles, CA.

Findings from the CAPELLA study reveal virologic suppression and a safety profile for multidrug-resistant HIV-1.

Sarah A. Schmalzle, MD, FIDSA

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