July 2024, we received the long-awaited results from the first of 2 studies evaluating twice-yearly injectable lenacapavir for preexposure prophylaxis (PrEP) against HIV infection. PURPOSE 1(NCT04994509), conducted in South Africa and Uganda, enrolled HIV-negative, sexually active cisgender women. Participants were randomly assigned to receive lenacapavir every 26 weeks plus an oral placebo, daily oral emtricitabine with tenofovir alafenamide (F/TAF) with an injected placebo, or daily oral emtricitabine-tenofovir disoproxil fumarate (F/TDF) with an injected placebo. Rather than including a placebo group, the study investigators compared each group’s efficacy against the background rate of HIV infection observed during screening.¹

The study’s results were highly promising: lenacapavir was 100% effective in preventing new HIV infections among the 2134 participants who received it. The study’s design also provided additional insights. Among the 8094 screened participants, the background HIV incidence was 2.41 per 100 person-years (95% CI, 1.82-3.19). In the lenacapavir group, the incidence was 0 per 100 person-years (95% CI, 0.00-0.19); for F/TAF, it was 2.02 per 100 person-years (95% CI, 1.44-2.76); and for F/TDF, it was 1.69 per 100 person-years (95% CI, 0.96-2.74).1 Not only did lenacapavir outperform the oral regimens (0 is difficult to surpass), but the rates for the oral regimens were not significantly different from the background HIV infection rate. The low adherence rates to the oral regimens were notable, with breakthrough infections largely occurring in patients who had low or undetectable concentrations of tenofovir.

The potential benefits of effective, twice-yearly injectable therapy are immense. Although PrEP has shown promise since the early success of F/ TDF, its major limitation has been adherence. Daily oral medications, though common for many people, require a committed and educated patient population, particularly when taken by healthy individuals not taking other medications. This challenge is exacerbated in populations where stigma surrounding HIV and PrEP is strong. Injectable medications such as lenacapavir could bypass this issue by offering a more private method of administration. Furthermore, a medication that only needs to be administered infrequently enhances privacy and simplifies treatment.

As this groundbreaking therapy nears availability, practical questions arise. The most pressing relate to cost. How can a therapy that costs thousands of dollars per year in the US be made accessible to individuals in high-need countries who cannot afford a fraction of that price? There is some time to address these concerns. Gilead Sciences is awaiting the results of PURPOSE 2 (NCT04925752) in late 2024 or early 2025 before filing for PrEP approval. The company has made promising statements, including that the new price will not be based on its current price for treatment-experienced patients, that they will pursue voluntary licensing partners in other countries, and that they will ensure a dedicated supply of medication until those partners are ready.²

We will have to see how well these commitments translate into action. Disparities in access to health care resources continue to fuel the spread of HIV, and the availability of new therapies can exacerbate inequities. Gilead has a historic opportunity to be a significant part of the solution.

References

1.Bekker LG, Das M, Abdool Karim Q, et al; PURPOSE 1 Study Team. Twice-yearly lenacapavir or daily F/TAF for HIV prevention in cisgender women. N Engl J Med. Published online July 24, 2024. doi:10.1056/NEJMoa2407001

2. Updated statement on global access planning for lenacapavir for HIV prevention. News release. Gilead Sciences, Inc. July 24, 2024. Accessed September 3, 2024.
https://www.gilead.com/news-and-press/company-statements/updated-statement-on-global-access-planning-for-lenacapavir-for-hiv-prevention

As concerns about monkeypox (Mpox) escalate, a recent Phase 2 clinical trial has demonstrated that the Modified Vaccinia Ankara-Bavarian Nordic (MVA-BN) vaccine is safe and immunogenic for adolescents aged 12-17. With children under 15 accounting for 70% of Mpox cases and 88% of deaths in the Democratic Republic of Congo (DRC), this study is particularly timely.

This study was presented at IDWeek, and co-author C. Buddy Creech, MD, MPH, discussed with Contagion the rationale for focusing on adolescents aged 12-17, highlighting the significant impact of Mpox on younger children in the DRC, “We recognize that this is not just a disease of adults with risk factors; it’s a disease in children too. In our study, we were already conducting an adult study where we compared the regular dose to one that we would administer just at the surface of the skin, just underneath the dermis, or inside the dermis.” He continued, “The most important piece is that the amount of antibodies that the teenagers produced in response to this vaccine was, if anything, slightly higher than that of adults, which gives us a lot of confidence moving forward. We looked at this in kids aged 12 to 17 years. They were healthy kids. We enrolled them, gave them the doses of vaccine, and then measured their immune response to the vaccine as well as any symptoms they might experience afterward.”

The study compared the immune responses of 315 adolescents to 211 adults aged 18-50, administering two subcutaneous doses of the vaccine 28 days apart. Key findings from the interim analysis indicated that both groups experienced similar rates of solicited systemic and local events, as well as unsolicited adverse events (AEs). Dizziness was reported by 3% of adolescents, with none in adults, aligning with trends observed in other adolescent vaccinations. Overall, the MVA-BN vaccine demonstrated good tolerance among participants. MVA-BN is currently licensed in the US for smallpox and Mpox but is not approved for those under 18, though it is available under emergency use in some countries.

Creech shared insights on the safety profile observed in adolescents compared to adults, particularly regarding dizziness, and how that may shape vaccination recommendations, “Dizziness stood out to us because we had about nine events in eight kids, but again, it aligns with what we see with other vaccines in this field. It’s just that teenagers can be a little emotional and anxious about vaccinations, which sometimes leads to that feeling of dizziness.”

Immunogenicity results were promising, with the geometric mean titer (GMT) for adolescents at Day 43 reaching 470.3 (95% CI: 422.3, 523.8), surpassing the adult response of 293.2 (95% CI: 249.8, 344.2) and achieving a GMT ratio of 1.6 (95% CI: 1.32, 1.95).

Creech discussed the next steps for researching the MVA-BN vaccine’s efficacy in younger children, and how do you plan to address the need for their protection, “What we need to do next, and what we are doing next, is optimizing the testing in the laboratory to look for very specific Mpox responses, because those assays are actually—or those tests are actually harder to do, so we’re working on that right now. But the more important issue is a vaccine is only as good as the public policies around getting those vaccines to those in need.”

In conclusion, the interim data support the safety and effectiveness of the MVA-BN vaccine in adolescents, meeting established non-inferiority criteria compared to adults. These findings underscore the need for vaccination in endemic regions, as well as the necessity for further evaluations in younger children to protect this vulnerable demographic against Mpox. Continued research is essential to fully assess the vaccine’s safety and efficacy across age groups, as Mpox remains a global public health threat.

Reference

Creech B, et. al. Safety and Immunogenicity of Mpox Vaccination in Adolescents Presentation #579 presented at IDWeek 2024. October 16-19, 2024. Los Angeles, CA.

Image credit: PF-Images, Stock.adobe.com

Outpatient parenteral antimicrobial therapy (OPAT) services are becoming more widespread across the US to improve transitions of care for patients requiring intravenous (IV) antibiotics outside the hospital setting.¹ Common disease states requiring IV antibiotics at discharge include endocarditis, bone and joint infections, and abscesses.

Study data on the effects of OPAT services consistently demonstrate their value regarding improved patient outcomes and lower health care costs. A publication in 2023 reported that approximately 40% of infectious diseases (ID) physicians in the US reported having a formal or dedicated OPAT program. The Infectious Diseases Society of America supports OPAT programs, characterizing them as “core quality indicators.” ID physicians, nurses, and pharmacists typically lead these services. Unfortunately, ID providers’ salaries are on the lower end of the spectrum compared with other specialties,^2-5 despite saving money for systems. Yet ID clinicians often conduct unbillable work to provide OPAT services. Therefore, the time spent doing these activities must be quantified so clinicians receive appropriate compensation for their time.

Clinicians from the University of North Carolina recently published a brief report on their OPAT program, which serves their affiliated academic hospital and ID clinic.⁶ An ID pharmacist and an advanced practice nurse lead their OPAT service. They manage patients who are discharged with an OPAT plan to the home setting but not nursing facilities and follow approximately 40 to 50 patients at any given time.

The researchers evaluated “OPAT time” for patients on the OPAT service between 2020 and 2022. OPAT time was defined as uncompensated time spent providing OPAT management and coordination outside clinic time (eg, monitoring and communication). There were 1064 OPAT courses with OPAT time documented, with most conditions being related to bone and joint infections, followed by diabetic foot infections, intra-abdominal infections, or endovascular infections. The median duration for OPAT was 35 days (IQR, 24-40), and more than half the patients had 1 or no outpatient clinic appointments.

The researchers found a 19% readmission rate within this population. Median weekly OPAT time per OPAT course was 27 minutes (IQR, 19-39 min), with more time typically spent on patients receiving vancomycin than on those not receiving vancomycin (median, 40 vs 23 min). Based on the results of this study, along with others that have shown the workload and cost savings of OPAT teams, the authors concluded that OPAT clinicians spend significant amounts of uncompensated time serving these complex patients. Hospital systems must work with payers to find ways to bill for these services.

The authors noted that limitations in their study include the underrepresentation of time spent managing OPAT activities and that pharmacists and nurses (who lead their team) are clinicians who don’t regularly bill for services. They also did not include data for patients discharged to facilities, where many patients complete their OPAT. Two points can be taken from this study: All clinicians should be compensated appropriately for their time, and all clinicians should be able to bill payers for services. ID clinicians have a wealth of knowledge that they use to manage complex patients, which should be accounted for in billing structures. Study findings published in 2023 by clinicians in Vancouver, Canada, reported the results of an incentive-based policy for OPAT. The authors evaluated whether introducing an incentive for providers would increase OPAT use. They concluded that there was no significant increase in OPAT use after the policy was put in place. This could indicate that money does not incentivize providers to make changes to improve patient care; that even without incentives, they are doing as much as possible. Alternatively, the incentive offered may not have interested clinicians, or the barriers to increasing OPAT services may have related to too few personnel compared with lack of compensation.⁷

Future evaluations of OPAT programs might include an economic analysis of costs avoided related to improved transitions of care, improved patient outcomes, shorter length of stay, and reduced readmissions. These can be evaluated with the time and level of care spent outside billable hours. Analyzing cost avoidance along with levels of appropriate compensation based on time spent on OPAT services would allow administrators and payers to determine the value of OPAT clinicians.

Featured article:
Schranz AJ, Swartwood M, Ponder M, et al. Quantifying the time to administer outpatient parenteral antimicrobial therapy: a missed opportunity to compensate for the value of infectious diseases. Clin Infect Dis. Published online May 14, 2024. doi:10.1093/cid/ciae262

References

1.Shah AB, Norris AH, eds. OPAT EHandbook. 3rd ed. Infectious Diseases Society of America; 2016. Accessed August 5, 2024. https://www.idsociety.org/journals–publications/opat-e-handbook/

2.Larnard J, Swords K, Taupin D, Padival S. From sea to shining IV: the current state of OPAT in the United States. Ther Adv Infect Dis. 2023;10:20499361231181490. doi:10.1177/20499361231181486

3.Lee YJ. “It’s hard to pay off your medical school loans in this kind of a job”: Doctors who can protect the world against pandemics are in short supply. Business Insider. Accessed July 24, 2024. https://www.businessinsider.com/infectious-disease-specialists-short-supply-low-paid-doctors-us-2020-5

4.New doctors aren’t choosing to go into infectious disease. https://www.npr.org/2022/12/13/1142594197/new-doctors-arent-choosing-to-go-into-infectious-disease. 2022. Accessed August 5, 2024.

5.Heys J. IDSA Treasurer: ID specialists are critical to the health preparedness workforce but need support. June 22, 2023. Accessed July 24, 2024. https://www.idsociety.org/science-speaks-blog/2023/idsa-treasurer-id-specialists-are-critical-to-the-health-preparedness-workforce-but-need-support/

6.Schranz AJ, Swartwood M, Ponder M, et al. Quantifying the Time to Administer Outpatient Parenteral Antimicrobial Therapy: A Missed Opportunity to Compensate for the Value of Infectious Diseases. Clin Infect Dis Off Publ Infect Dis Soc Am. Published online May 14, 2024:ciae262. doi:10.1093/cid/ciae262

7.Staples JA, Ho M, Ferris D, et al. Physician Financial Incentives for Use of Outpatient Intravenous Antimicrobial Therapy: An Interrupted Time Series Analysis. Clin Infect Dis. 2023;76(12):2098-2105. doi:10.1093/cid/ciad082