511 - RSV Prophylaxis, PrEP to Prevent HIV, Preventing Physician Suicide
Take 3 – Practical Practice Pointers©
From the CDC: Seasonal Vaccines, Part 2
1) Respiratory Syncytial Virus (RSV) prophylaxis
Alert readers will recall that we recently covered (in Take 3 #506) a new adult RSV vaccine for patients aged 60+ with certain risk factors for lower respiratory tract infection. The Advisory Committee on Immunization Practices (ACIP) approved it as a “shared decision making” recommendation – meaning we should discuss it with our patients.
The ACIP has also approved a monoclonal antibody injection (nirsevimab; not technically a “vaccine” but provides passive immunity) for prevention of RSV infection in all infants as a routine or general recommendation.
· Infants aged < 8 months entering their first RSV season should get a single-dose injection; a 50 mg dose for children weighing < 5 kg (11 lbs.) and 100 mg for children weighing more than that.
· Children aged 8-19 months with risk factors for severe RSV infection entering their second RSV season should get a single dose of 200 mg. This injection should be administered as 2 100 mg injections in different sites. The risk factors for severe disease are (from the MMWR):
o Children with chronic lung disease of prematurity who required medical support (chronic corticosteroid therapy, diuretic therapy, or supplemental oxygen) any time during the 6-month period before the start of the second RSV season.
o Children with severe immunocompromise.
o Children with cystic fibrosis who have either 1) manifestations of severe lung disease (previous hospitalization for pulmonary exacerbation in the first year of life or abnormalities on chest imaging that persist when stable) or 2) weight-for-length <10th percentile.
o American Indian or Alaska Native children.
· Nirsevimab can be given along with the usual childhood vaccines. It should be given shortly before the onset of the RSV season - currently October through March for most of the US (other areas should monitor RSV seasonal patterns). It can be given during the birth hospitalization, or within 1 week of discharge during RSV season.
The ACIP’s decision to approve these preventive injections underscores the considerable burden of RSV infection in US children under age 5: 50-80,000 hospitalizations and 4-600 deaths occur every year. This injection replaces palivizumab (Synagis), which was indicated for fewer patients, was much more expensive, and had to be given monthly. The effectiveness of the early infancy dose (in per-protocol evaluations of premature and term infants compared to placebo) was 79% to prevent “medically-attended RSV”, 80% to prevent RSV hospitalization and 90% to prevent RSV ICU admission. There were no deaths in either arm of the studies and there was no difference in severe adverse events between arms. The study in older children (8-19 months) compared nirsevimab to palivizumab. There was no difference in serious adverse events, but the evidence of effectiveness to prevent RSV lower respiratory tract infection was “extrapolated from pharmacokinetic data.”
The cost effectiveness data are telling. For infants < 8 months, nirsevimab costs $102,811 per quality-adjusted life year (QALY). For high-risk children 9-18 months, nirsevimab is estimated to cost $1,557,544 per QALY.
There’s no agreed-upon cost per QALY value that makes a preventive intervention worthwhile. Numbers up to $200,000 are commonly cited, so this makes the RSV injection for older children very expensive, indeed. Still, RSV is the most common cause of hospitalization and associated morbidity in US children. We are in an unusual position of having the evidence for the highest risk children be the least convincing while also estimating very high costs. Hopefully, we will have better evidence and cost estimates after some regular use. Of note, this recommendation is coming rather late in the year, so hospital systems are racing to try to get these programmed into their EHR systems.
· Jones JM. Use of Nirsevimab for the Prevention of Respiratory Syncytial Virus Disease Among Infants and Young Children: Recommendations of the Advisory Committee on Immunization Practices — United States, 2023. MMWR Morb Mortal Wkly Rep. 2023;72. Link
· GRADE: Nirsevimab, Season 1 | CDC. Link
From the USPSTF
2) Preexposure Prophylaxis (PrEP) to Prevent HIV
An estimated 1.2 million persons in the US currently have HIV. In 2020, there were an estimated 30,000 new diagnoses with 80% occurring among adolescent and adult men. HIV is primarily acquired via sexual activity or injection drug use. Men who have sex with men are most affected by HIV, accounting for 68% of new HIV diagnoses in 2020. Likelihood of HIV transmission is highest with needle-sharing injection drug use and condomless receptive anal intercourse.
There are also racial and ethnic disparities in the incidence of HIV, with 42% of new diagnoses occurring among Black persons, 27% among Hispanic/Latino persons, and 26% among White persons in 2020. Although treatable, HIV is not curable and has significant health consequences. Therefore, effective strategies to prevent HIV are an important public health and clinical priority.
The USPSTF recently published recommendations regarding the use of preexposure prophylaxis (PrEP) with antiretroviral therapy for the prevention of HIV acquisition in adolescents and adults who do not have HIV and are at increased risk. The Task Force recommends that clinicians prescribe PrEP using effective antiretroviral therapy to persons at increased risk to decrease the risk of acquiring HIV. (A recommendation) The USPSTF concludes with high certainty that there is a substantial net benefit from the use of effective antiretroviral therapy.
The USPSTF recommends that the following persons be considered for PrEP:
1. Sexually active adults and adolescents weighing at least 35 kg (77 lb) who have engaged in anal or vaginal sex in the past 6 months and have any of the following:
o A sexual partner who has HIV (especially if the partner has an unknown or detectable viral load).
o A bacterial sexually transmitted infection (STI) (syphilis, gonorrhea, or chlamydia for men who have sex with men and transgender women; gonorrhea and syphilis for heterosexual women and men) in the past 6 months.
o A history of inconsistent or no condom use with sex partner(s) whose HIV status is not known; assessing risk in conversation with the patient and considering factors such as number of partners, the specific sexual activities a person engages in, and whether their sex partner or partners are in a group with a higher prevalence of HIV (eg, men who have sex with men or with men and women, transgender women, persons who inject drugs, and persons who engage in transactional sex).
2. Persons who inject drugs and have a drug-injecting partner who has HIV or who shares injection equipment.
Currently, several medications are approved by the FDA for use as PrEP. Oral tenofovir disoproxil fumarate/emtricitabine (TDF/FTC - Truvada) and injectable cabotegravir (Apretude) are approved for use in at-risk adults and adolescents weighing at least 35 kg (77 lb). Oral tenofovir alafenamide/emtricitabine (TAF/FTC – Descovy) is approved for use in at-risk adults and adolescents weighing at least 35 kg (77 lb), excluding individuals at risk from receptive vaginal sex. No PrEP medications have FDA approval for the indication of reducing the risk of acquiring HIV via injection drug use, but CDC guidelines note that persons who inject drugs are likely to benefit from PrEP with any FDA-approved PrEP medication. FDA labeling permits the use of TDF/FTC in pregnant persons. It also permits the use of TDF/FTC in persons who are breastfeeding and recommends that the potential benefits should be considered along with any potential adverse effects on the breastfed child.
If we don’t ask about risk, our patients may not share that risk with us, particularly in adolescents, so inquiring is vital. Be aware the generic formulation of tenofovir/ emtricitabine is presently available on GoodRx for $30/month. The other medications are not presently available in generic form, and without insurance coverage will be cost-prohibitive for most patients.
USPSTF. Preexposure Prophylaxis to Prevent Acquisition of HIV. JAMA August 22/29, 2023;330(8):736-745. Link
From PeerRxMed ( www.PeerRxMed.org )
3) No One Should Struggle Alone
“We need to be better at helping each other.” Physician colleague who came within minutes of committing suicide
We know the work we do as physicians and other healthcare clinicians is challenging and can be incredibly emotionally taxing. A conversation recently with a colleague who reached out for support due to their feeling that they were at their emotional “wits end” recalled another colleague who 6 years ago came within minutes of choosing to take her life through suicide. Over the years since she has shared details with me of that painful time in her life and the healing journey she has taken.
When we last spoke, she was far enough away from that intensely dark and emotionally raw time to have gained deeper insight. One of the things she told me (and has given me permission to share) speaks directly to why it is so essential to have a buddy (or buddies) who understands what it is like to travel this professional journey called healthcare: “I’m not the kind of person who would ever consider something like suicide – so I thought. But I broke, and the level of emotional pain I was feeling is difficult to describe. It had to be quite obvious to others that something was wrong. I believe they wanted to help, but none of them seemed comfortable in reaching out to me and when they did, it was easy to push them away.” She concluded, “We need to be better at helping each other.”
National Physician Suicide Awareness Day | NPSA Day will be on Sunday, September 17th this year. Started in 2018, the vision for this initiative is that this day will serve as a call to action for all of us to re-commit to breaking down stigma, opening the conversation, decreasing the fear of consequences, recognizing warning signs and learning to approach our colleagues who may be at risk for suicide. Of course, it is a tragedy to think that we even need a day to raise awareness of physician suicide, but the statistics indicate that on average, one of our physician colleagues choses to take their life every day, and these statistics do not account for our NP, PA, PhD, PharmD, Allied health, and nursing teammates, all of whom, as we know, are struggling mightily as well. Additionally, the 2023 Medscape Physician Suicide Report indicates 1 in 10 physicians have had thoughts of suicide, yet 40% told no one about them.
According to Psychiatrist Michael Meyers, MD, author of the book The Physician as Patient, when a colleague shares that they are having suicidal thoughts, the first step is to thank them for sharing the information; “I’m sure that wasn’t easy, but I appreciate that you respect me enough to share with me. Let’s talk more.” Then ask what you can do to help. If, on the other hand, you note that someone isn’t doing well, reach out and compassionately let them know of your concern and that you’d like to help, and don’t hesitate to ask directly if they’ve considered suicide.
The pressures we face with the work we do are extraordinary. Given this, the entire purpose of the PeerRxMed process is to ensure that “no one cares alone.” It is vital that every one of us has someone we are certain we can reach out to in good times and bad and we know they will be there for us. This is a person who knows us well enough that they would recognize when were weren’t doing well and would feel very comfortable and even insistent in ensuring we received the help we needed. The stakes are too high to do otherwise. Let’s all commit to becoming better at helping each other. If you’re not signed up for PeerRx, get a buddy and do so (if you’re not sure how, e-mail me). If you are, encourage others to sign up as well. This is too important to leave to chance. The life that we save could be someone close to us, or even our own.
Carilion Clinic Department of Family and Community Medicine
Feel free to forward Take 3 to your colleagues. Glad to add them to the distribution list.
Mark and John