Expert commentary: A focus on RSV vaccination, mpox and HIV PrEP

RSV vaccination

RSV is a common respiratory virus that spreads in the fall and winter seasons. Although infections are typically mild in nature with cold-like symptoms in most healthy children and adults, RSV can progress to more severe disease in certain populations such as infants, older adults and those with certain chronic conditions (i.e., chronic lung disease, immunocompromised conditions). In fact, statistics presented at IDWeek from recent Centers for Disease Control and Prevention (CDC) data indicate that RSV leads to between 100,000-160,000 and 58,000-80,000 hospitalizations in adults 60 years and older and children younger than 5 years, respectively, each year in the United States.

Taylor Morrisette, Pharm.D., M.P.H.

Furthermore, compared with older adults, a higher proportion of those younger adults hospitalized due to RSV were Black or Hispanic. These high and disproportionate rates of hospitalization highlight the importance of efficacious and safe prophylaxis strategies and mitigation of healthcare disparities.

Although monoclonal antibody products are available as preventive strategies for infants and young children, these are not indicated to protect adults at high risk for severe disease. Prior to the availability of a vaccine, some older adults were extremely vulnerable for progressing to advanced illness. Fortunately, the FDA has recently approved several RSV vaccinations in 2023 and 2024 for use in adults and in pregnant adults to protect infants at birth. Currently, Arexvy (GSK), Abrysvo (Pfizer) and mRESVIA (Moderna) are indicated for adults at least 60 years of age as a single dose. The 2024-2025 updates to the CDC recommendations were discussed at IDWeek. Previously, the public health agency had recommended a shared decision-making approach to RSV vaccination among people aged 60 and older. Throughout the 2024-2025 season, the CDC shifted to an outright recommendation for RSV vaccination for those 75 and older and those aged 60 to 74 years who are at increased risk of experiencing a severe case of RSV. Abrysvo is also indicated in adults who are between 32 and 36 weeks pregnant during the seasonal time frame to protect their babies from lower respiratory tract disease. Further, Pfizer announced just days following IDWeek 2024 that the FDA had also approved Abrysvo for adults aged 18 to 59 years who are at increased risk of lower respiratory tract disease caused by RSV, based on results from the pivotal phase 3 clinical trial MONeT.

Following 2023-2024, the first season in which RSV vaccines were made available in the United States for older adults, many experts have become interested in the vaccine’s effectiveness in the real-world setting. As such, a recent population-based analysis presented at IDWeek 2024 by Heidi Ransohoff, M.P.H., of Los Angeles County Department of Public Health, that described the risk of laboratory-confirmed RSV infection in adults 60 years or older by vaccination status, in Los Angeles County, California, was noteworthy. RSV vaccination data were used from the California Immunization Registry, and RSV- positive case data were retrieved from the Los Angeles County Department of Public Health (required reporting). In the analysis of data on more than approximately 2 million residents at least 60 years of age, the risk of electronic laboratory-reported RSV infection was 5.1 times higher among unvaccinated persons than among those who were vaccinated. The authors emphasized the importance of future data evaluating hospitalization and death rates among persons vaccinated and unvaccinated to compare the incidence of severe disease.

Racial and ethnic healthcare disparities are important to address from an equity standpoint as they may adversely affect groups of people that systematically experience greater hindrances to health. Elie Saade, M.D., M.P.H., of University Hospitals of Cleveland, began the discussion of his and his colleagues’ research by noting that low vaccination rates can be influenced by things such as socioeconomic status, barriers to access and racial disparities, and they highlighted the impact of the COVID-19 pandemic on a heightened vaccine hesitancy. They set out to evaluate if social vulnerability and race were significant factors of RSV vaccine uptake. Following an analysis of nearly 160,000 persons aged at least 60 years from the CDC Social Vulnerability Index 2022 databases, Black individuals and those with higher social vulnerability indexes were less likely to receive an RSV vaccination after various statistical adjustments were made.

Helen Chu, M.D., M.P.H., of the University of Washington, presented CDC data regarding maternal vaccination. In pregnant individuals aged 18 to 49 years, overall vaccination uptake rate in the 2023-2024 season was approximately 18% as of early 2024. Revised data recently reported by the CDC show an increased rate of over 30%. Real-world data presented from the Kaiser Permanente Vaccine Study Center reported similar figures, with vaccination uptake increasing with age and lowest rates among Black and Hispanic patients. Chu described the many challenges with maternal vaccine implementation, including a low awareness of RSV among parents and general practitioners, a narrow administration window (between 32 and 36 weeks of gestation), patient concerns about vaccine safety and the lack of adequate RSV vaccine availability in obstetrics and gynecology offices. She went on to discuss various unanswered questions that should be studied, such as vaccine effectiveness and the need for repeat vaccination during repeat pregnancies. Further promotion of RSV vaccine uptake and actions to mitigate healthcare disparities are necessary throughout the upcoming respiratory virus season.

Mpox

Mpox is a viral disease caused by the mpox virus, an orthopoxvirus related to smallpox that mainly spreads through close contact with someone who is infected. Although the first human case was reported to have occurred decades ago, mpox was neglected in certain areas of the world which, in part, led to a global outbreak in 2022. At IDWeek 2024, Placide Mbala-Kingebeni, M.D., Ph.D., M.S.P.H., presented data from the World Health Organization on the global epidemiology of mpox that showed approximately 100,000 confirmed cases in more than 100 countries reported thus far from this recent outbreak. The recent worldwide surge linked with the high morbidity associated with this disease underscores the importance of highly available, efficacious and safe therapeutic and prophylactic options.

Tecovirimat is an antiviral drug originally developed and stockpiled for smallpox preparedness that was repurposed to treat mpox. Information regarding its efficacy and safety as a treatment for mpox is limited. Olivier Tshiani Mbaya, M.D., of the Frederick National Laboratory for Cancer Research, reported data on tecovirimat for the treatment of mpox in the Democratic Republic of Congo, the area of the world most affected by mpox, from a randomized, placebo-controlled trial, PALM007, sponsored by the National Institutes of Health. The primary objective of this trial was to compare the efficacy of tecovirimat plus standard of care (SOC) with placebo plus SOC for mpox, assessed by time to lesion resolution. Importantly, key elements of the study included hospitalization for the 14-day treatment duration and complete nutrition support necessary to promote adequate drug absorption. The investigators randomly assigned approximately 300 participants to each treatment arm. The results showed no significant differences in time to lesion resolution between the two groups, an indication that tecovirimat may not be effective against mpox, although subgroup analyses suggested a treatment effect specific to a particular study site. Furthermore, it is important to note geographical distinctions in mpox types (clades).

Jynneos is another example of an agent repurposed from smallpox research. It is a vaccine produced from a live, attenuated orthopoxvirus that is FDA approved to prevent mpox in adults 18 years or older. Although other studies of Jynneos are available that show vaccine effectiveness, multiple studies are ideal to generate reliable and real-world evidence of vaccine effectiveness estimates.

Lauren Granskog, M.P.H., of the California Department of Public Health and University of California, presented data comparing the clinical severity of mpox disease in individuals who had been vaccinated with Jynneos and those who had not. Analysis of the data showed that among persons infected with mpox, including those living with HIV, vaccination was associated with a less severe clinical presentation with less lesion dissemination and fewer prodromal symptoms.

In summary, mpox vaccines are recommended for any persons at risk because of the ongoing outbreak but are not recommended for individuals who have recovered from mpox. Additionally, a booster dose is not recommended for individuals who were vaccinated in 2022 when the global outbreak started.

HIV PrEP

Due to the lack of a therapeutic cure for and vaccination against HIV and AIDS, most experts consider traditional preventive measures linked with PrEP as the main measures for preventing infection and optimizing outcomes in persons at risk for developing disease. Given that most PrEP regimens are oral drugs administered daily with suboptimal uptake and adherences issues, long-acting parenterally administered medications are vital to prevent the necessity of daily oral adherence and frequent outpatient clinic visits.

Lenacapavir is an HIV-1 capsid inhibitor that is being study as a PrEP option through the subcutaneous (SQ) route with twice-yearly administration. Results of the PURPOSE 1 trial published in the New England Journal of Medicine showed that none of the 2,134 cisgender women randomly assigned to twice-yearly lenacapavir developed HIV. An interim analysis of the PURPOSE 2 trial results was presented at IDWeek 2024 by Colleen Kelley, M.D., M.P.H., on behalf of the PURPOSE 1 and PURPOSE 2 study team. PURPOSE 2 was a randomized controlled trial conducted among cisgender men, transgender men, transgender women and gender nonbinary individuals that compared SQ lenacapavir twice yearly (n = 2,179) with oral Truvada (emtricitabine/tenofovir disoproxil fumarate) daily (n = 1,086) for PrEP. Following a median follow-up duration of nearly one year, two HIV infections occurred in participants receiving lenacapavir compared with nine among participants receiving Truvada. Overall, lenacapavir was shown to reduce HIV infections by 100% in PURPOSE 1 and by 96% in PURPOSE 2 in comparison to background HIV incidence. Furthermore, lenacapavir HIV prophylaxis efficacy was shown to be superior to Truvada through secondary analyses, with comparable adverse effects.

Author Affiliations: Department of Clinical Pharmacy & Outcomes Sciences, Medical University of South Carolina College of Pharmacy, Charleston, South Carolina; Department of Pharmacy Services, Medical University of South Carolina Health, Charleston.

Correspondence: Taylor Morrisette, PharmD, MPH; 173 Ashley Avenue, CP 134, Charleston, SC 29425; 843-792-2138. Email: Tam271@musc.edu