Update on Long-Acting Regimens for the Treatment of HIV-1

Viral suppression is one of the major goals of the Centers for Disease Control and Prevention (CDC) Ending the HIV Epidemic in the US (EHE) initiative.1 Viral suppression is defined in this context as fewer than 200 copies of HIV per mL of blood by 2025 in at least 95% of the individuals infected with HIV in the US, with the further goal of remaining at or above 95% suppression in 2030 (Figure 1).2 This is important because viral suppression not only minimizes an individual’s HIV disease activity but also reduces transmission of HIV from infected individuals to their uninfected sexual partners. Large studies have demonstrated that if viral load is further suppressed to the point that HIV becomes undetectable, risk of transmission via sexual activity is largely eliminated.



In turn, adherence to antiretroviral (ART) medication is generally considered to be the strongest predictor of HIV treatment success. However, even assuming that the patient is promptly linked to suitable care and interventions upon diagnosis (Figure 2),2 poor long-term adherence remains a notable challenge and is associated with virologic failure, disease progression, and adverse effects including increased mortality.2,3 Patients who take a daily oral ART regimen may have problems with adherence due to “pill fatigue,” dosing complexity and its demands on attention, and subsequent lost motivation. Other barriers to patient adherence include the stigma related to HIV status and concern about inadvertent disclosure, disruptive life events or long-term instability in living conditions, and mental or emotional comorbid conditions.



Long-acting (LA) ART regimens may offer advantages in ensuring medication adherence. A drug combination administered at longer intervals, as opposed to one self-administered daily, may reduce stigma and patients’ cognitive and emotional loads. Physician-patient contact may increase, providing further potential to ensure full adherence. An injectable form of LA ART therapy may also improve absorption, reduce gastrointestinal side effects, and circumvent difficulty in swallowing pills.4

A Long-Acting Injectable Regimen

To date, combination therapy with cabotegravir plus rilpivirine,5 administered by intramuscular injection, is the only US Food and Drug Administration (FDA)-approved complete LA regimen for HIV-1 viral suppression. Cabotegravir is an HIV-1 integrase strand transfer inhibitor (INSTI); rilpivirine is an HIV-1 non-nucleoside reverse transcriptase inhibitor (NNRTI). Cabotegravir and rilpivirine are most commonly used in combination, although cabotegravir is also approved as a single agent as oral preexposure prophylaxis.
 
Phase 3 trials demonstrated cabotegravir plus rilpivirine to be noninferior to standard-of-care oral ART. In the phase 3 FLAIR study (ClinicalTrials.gov Identifier: NCT02938520), ART-naive patients received oral induction therapy comprising dolutegravir, abacavir, and lamivudine for 20 weeks.6 Participants who had a plasma HIV-1 level of fewer than 50 copies per mL were randomly assigned 1:1 to continue the current oral therapy or switch to LA therapy, which required a 4-week period of oral lead-in therapy with cabotegravir and rilpivirine, for a 48-week study period. At the initial 48-week endpoint, LA cabotegravir plus rilpivirine was found to be noninferior to the standard-of-care regimen.
 
In a subsequent extension phase of FLAIR, patients initially assigned to remain on oral therapy were given the option to extend their participation by switching to LA cabotegravir plus rilpivirine, either on a direct-to-injection basis or following oral lead-in therapy. Efficacy, safety, and tolerability were comparable across the 2 extension switch groups. In reporting 124-week results for the LA therapy group from the initial phase of FLAIR, the investigators concluded that LA cabotegravir plus rilpivirine offered durability as maintenance therapy.
 
The randomized phase 3 ATLAS study (ClinicalTrials.gov Identifier: NCT02951052)  tested LA cabotegravir plus rilpivirine in treatment-experienced patients who were assigned to continue their current therapy or switch to the LA cabotegravir plus rilpivirine after the oral lead-in period of 4 weeks.7 This investigation, which stratified patients into subgroups based on the drug classes represented in their baseline ART regimen, showed LA therapy to be noninferior to the baseline regimens at 48 weeks in terms of efficacy, safety, and tolerability.
 
Subsequent phase 2 and phase 3 studies, including ATLAS-2M (ClinicalTrials.gov Identifier: NCT03299049), have demonstrated highly comparable clinical results whether participants received LA cabotegravir plus rilpivirine every 8 weeks or every 4 weeks.8 Through week 96, participants more strongly preferred administration every 8 weeks compared with 4-week (injection) or daily (oral) dosing intervals. More recent reporting at 152 weeks9 has demonstrated durable viral suppression with administration at both 4-week and 8-week intervals. The most common drug-related adverse event in these studies has been injection-site reaction, followed by pyrexia and fatigue.
 
In 2021 the FDA approved the LA cabotegravir plus rilpivirine regimen for administration every 4 weeks; in early 2022, the FDA expanded its approval to administration every 8 weeks.10 The European Medicines Agency (EMA) has also approved this regimen at both the 4-week and 8-week intervals.11


Cabotegravir plus rilpivirine regimen adverse effects
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Adverse effects commonly reported with cabotegravir plus rilpivirine include injection site reactions, pyrexia, fatigue, headache, musculoskeletal pain, nausea, sleep disorders, dizziness, and rash.

Who Is Eligible for Long-Acting Therapy?

Currently, LA cabotegravir plus rilpivirine is recommended for patients with HIV-1 twelve years of age or older weighing at least 35 kg and without a history of treatment failures/viral resistance to either cabotegravir or rilpivirine.10 Notably, a pooled analysis of data from the ATLAS and FLAIR trials12 showed that mutations conferring drug resistance were widespread among the small proportion of patients receiving LA cabotegravir plus rilpivirine with confirmed virologic failure. Candidates for this treatment regimen also should be willing and able to commit to injection visits every 4 or 8 weeks.
 
The LA cabotegravir plus rilpivirine regimen is contraindicated in patients with a history of hypersensitivity reaction to either agent, and in patients who concurrently receive carbamazepine, oxcarbazepine, phenobarbital, phenytoin, rifabutin, rifampin, rifapentine, systemic dexamethasone, or St John’s wort. There is a risk of torsade de pointes when given in combination with some antibiotics.10
 
Patients with hepatitis B virus (HBV) were excluded from both the FLAIR and ATLAS trials. Cabotegravir and rilpivirine have not demonstrated efficacy against HBV13; this limits the clinical utility of these drugs in patients who are coinfected with HIV-1 and HBV. Given the exclusion criteria of the ATLAS and FLAIR trials, there is also limited information regarding whether the LA cabotegravir plus rilpivirine regimen is suitable for patients who are pregnant, those with serious hepatic or renal pathology, patients with poorly-controlled HIV infection, and young children. These trials excluded patients with viral mutations associated with resistance to INSTIs or NNRTIs, except for the HIV-1 RT K103N mutation in isolation; clinicians have been advised to test patient who are candidates for this regimen for resistance-associated mutations, given that these mutations appear to be associated with virologic failure of this regimen.14
 
Finally, it is important for patients to understand that treatment adherence remains essential to maintaining HIV-1 suppression, even though they will not self-administer their medications daily. Patients who find it challenging to attend 4-week (or 8-week) visits for maintenance injections, and clinics facing challenges (eg, with staffing, other resources) offering routine visits, must bear in mind the risk of viral rebound and evolution of drug resistance if patient adherence is incomplete. Clinics offering LA cabotegravir plus rilpivirine must maintain cold-chain storage for these medications and should designate staff resources, time, and clinic space for injection visits and dose preparation.
 
Although improved adherence is commonly considered a key motivator behind implementing a long-acting regimen such as cabotegravir plus rilpivirine, there is a lack of real-world data regarding whether this LA regimen indeed lowers barriers to adherence. These data will likely emerge from future long-term, prospective studies.

LA Cabotegravir Plus Rilpivirine Combination Injection: Administration and Dosage

During the optional oral lead-in period, which allows the clinician to assess drug tolerability, the recommended daily dosage is 30 mg cabotegravir plus 25 mg rilpivirine, administered for at least 28 days5 or until the first injection dose is given (Table). The loading dose for the complete LA injection regimen, if administered every 4 weeks, consists of 3 mL injections each of cabotegravir (600 mg) and rilpivirine (900 mg), generally in opposite gluteal muscles. Maintenance administration begins 1 month after these initiation injections; the monthly dose is 2 mL injections each of cabotegravir (400 mg) and rilpivirine (600 mg).
 
If this therapy is administered every 8 weeks, the loading dose includes 3-mL injections each of cabotegravir (600 mg) and rilpivirine (900 mg) after the oral lead-in period and 1 month after. Maintenance administration begins 2 months after the second loading dose at the same dose (Table).5



Results of the aforementioned phase 3 trials indicated that receipt of injection approximately 7 days from the monthly (or bimonthly) scheduled date was acceptable. If the patient misses, or plans to miss, a scheduled LA injection, bridging with oral medication is recommended to maintain virological drug activity. This relies on the availability of the cabotegravir and rilpivirine oral formulations, such as those used during the lead-in to the LA injection study regimens. Ideally clinics and patients should plan to secure those equivalents in advance,15 because their availability through community pharmacies cannot be assured. Cabotegravir, in particular, is not available at pharmacies.16

Additional Existing and Emerging Options for Use of LA HIV Treatment Regimens

Ibalizumab is a humanized immunoglobulin G4 (IgG4) antibody approved for treatment of multidrug-resistant HIV infections. It is not a complete regimen, but is used in combination with the patient’s existing or optimized background ART regimen.17 The loading dose is 2000 mg administered intravenously followed by maintenance intravenous infusions of 800 mg, saline-diluted, every 2 weeks. It has the disadvantage of more frequent administration than other LA drugs and requires patients to adhere to their previous ART regimens. Nevertheless, the advent of this drug may represent a step toward less-than-daily dosing for patients with multidrug-resistant HIV-1.
 
Numerous other ART drugs and novel formulations of existing ART are in development. Advances in LA ART will likely address and overcome the disadvantages and limitations of currently available LA regimens.15 For example, subcutaneous implant formulations, currently in preclinical and early phase studies, may permit longer release time with improved cellular uptake. Other future LA ART may be self-administered at home by subcutaneous injection. Reduced volume of injectable doses may limit the frequent injection site reactions secondary to relatively large (2 mL and 3 mL) intramuscular injections. Such advances should help to address challenging medication adherence problems and possibly reduce the need for oral lead-in therapy.

References

1. Fauci AS, Redfield RR, Sigounas G, Weahkee MD, Giroir BP. Ending the HIV epidemic: a plan for the United States. JAMA. 2019;321(9):844-845. doi:10.1001/jama.2019.1343

2. Centers for Disease Control and Prevention. Monitoring selected national HIV prevention and care objectives by using HIV surveillance data—United States and 6 dependent areas, 2019. HIV Surveillance Supplemental Report 2021;26(No. 2). Published May 2021. Accessed September 24, 2022. https://www.cdc.gov/hiv/library/reports/hiv-surveillance/vol-26-no-2/index.html

3. Nachega JB, Marconi VC, van Zyl GU, et al. HIV treatment adherence, drug resistance, virologic failure: evolving concepts. Infect Disord Drug Targets. 2011;11(2):167-174. doi:10.2174/187152611795589663

4. Akinwunmi B, Buchenberger D, Scherzer J, et al. Factors associated with interest in a long-acting HIV regimen: perspectives of people living with HIV and healthcare providers in four European countries. Sex Transm Infect. 2021;97(8):566. doi:10.1136/sextrans-2020-054648

5. Cabenuva. Prescribing information. ViiV Healthcare; 2022. Accessed September 24, 2022. https://gskpro.com/content/dam/global/hcpportal/en_US/Prescribing_Information/Cabenuva/pdf/CABENUVA-PI-PIL-IFU2-IFU3.PDF

6. Orkin C, Arasteh K, Górgolas Hernández-Mora M, et al. Long-acting cabotegravir and rilpivirine after oral induction for HIV-1 infection. N Engl J Med. 2020;382(12):1124-1135. doi:10.1056/NEJMoa1909512

7. Swindells S, Andrade-Villanueva JF, Richmond GJ, et al. Long-acting cabotegravir and rilpivirine for maintenance of HIV-1 suppression. N Engl J Med. 2020;382(12):1112-1123. doi:10.1056/NEJMoa1904398

8. Jaeger H, Overton ET, Richmond G, et al. Long-acting cabotegravir and rilpivirine dosed every 2 months in adults with HIV-1 infection (ATLAS-2M), 96-week results: a randomised, multicentre, open-label, phase 3b, non-inferiority study. Lancet HIV. 2021;8(11):E679-E689. doi:10.1016/S2352-3018(21)00185-5

9. Overton ET, Richmond G, Rizzardini G, et al. Long-acting cabotegravir + rilpivirine every 2 months: ATLAS-2M week 152 results. Poster presented at: Conference on Retroviruses and Opportunistic Infections 2022; February 12-16, 2022; Seattle, Washington; Poster 479.  

10. ViiV Healthcare announces US FDA approval of Cabenuva (cabotegravir, rilpivirine) for use every two months, expanding the label of the first and only complete long-acting HIV treatment. ViiV Healthcare. Published February 1, 2022. Accessed September 24, 2022. https://viivhealthcare.com/hiv-news-and-media/news/press-releases/2022/january/viiv-healthcare-announces-fda-approval-of-cabenuva-for-use-every-two-months/

11. First long-acting injectable antiretroviral therapy for HIV recommended approval. European Medicines Agency. Published October 16, 2020. Accessed September 24, 2022. https://www.ema.europa.eu/en/news/first-long-acting-injectable-antiretroviral-therapy-hiv-recommended-approval

12. Rizzardini G, Overton ET, Orkin C, et al. Long-acting injectable cabotegravir + rilpivirine for HIV maintenance therapy: week 48 pooled analysis of phase 3 ATLAS and FLAIR trials. J Acquir Immune Defic Syndr. 2020;85(4):498-506. doi:10.1097/QAI.0000000000002466

13. Bollinger RC, Thio CL, Sulkowski MS, McKenzie-White J, Thomas DL, Flexner C. Addressing the global burden of hepatitis B virus while developing long-acting injectables for the prevention and treatment of HIV. Lancet HIV. 2020;7(6):E443-E448. doi:10.1016/S2352-3018(19)30342-X

14. McGowan JP, Fine SM, Vail RM, et al; on behalf of Medical Care Criteria Committee of the New York State Department of Health AIDS Institute (NYSDOH AI). Use of injectable CAB/RPV LA as replacement ART in virally suppressed adults. Johns Hopkins University; 2022. Accessed September 24, 2022.

15. Scarsi KK, Swindells S. The promise of improved adherence with long-acting antiretroviral therapy: what are the data? J Int Assoc Provid AIDS Care. Published online April 27, 2021. doi:10.1177/23259582211009011

16. Preparing for long-acting antiretroviral treatment. American Academy of HIV Medicine. February 25, 2021. Accessed September 24, 2022. https://aahivm.org/wp-content/uploads/2021/03/Long-Acting-ARVs-_Final-2-25-21_PDF.pdf

17. Emu B, Fessel WJ, Schrader S, et al. Forty-eight-week safety and efficacy on-treatment analysis of ibalizumab in patients with multi-drug resistant HIV-1. Open Forum Infect Dis. 2017;4(suppl 1):S38-S39. doi:10.1093/ofid/ofx162.093 

Posted by Haymarket’s Clinical Content Hub. The editorial staff of Clinical Advisor had no role in this content’s preparation.

Reviewed October 2022

Infections Reported After Single Dose of Monkeypox Vaccine

Overall, 90 patients tested positive for monkeypox 1 day or more after vaccination. Credit: Getty Images.

HealthDay News — Most cases of monkeypox that occur after vaccination with the modified Vaccinia Ankara-Bavarian Nordic vaccine (MVA-BN) occur within 14 days of receipt of the first dose, according to a research letter published online in the Journal of the American Medical Association.

Aniruddha Hazra, MD, from Howard Brown Health in Chicago, and colleagues describe monkeypox infections after a single dose of MVA-BN at a monkeypox testing and vaccination site. Howard Brown Health started performing real-time reverse transcriptase-polymerase chain reaction tests to detect monkeypox in May 2022; MVA-BN was administered to eligible individuals on June 28, 2022. Patients who tested positive for monkeypox after vaccination and through September 9, 2022, were included.

The researchers found that 400 patients tested positive for monkeypox during the study period, and 7339 individuals received their first dose of MVA-BN. Overall, 90 patients tested positive for monkeypox 1 day or more after vaccination: 37 and 32 cases occurred at 1 to 7 and 8 to 14 days after vaccination, respectively (77% of all cases). There was a median of 8.5 days between vaccination and infection. Overall, 36.2% of the cases occurring one to 14 days after vaccination were in people with HIV, 96% of whom were virologically suppressed. Of the early postvaccination cases without HIV infection, 54% were using preexposure prophylaxis. Eight monkeypox cases occurred more than 28 days after the first dose of MVA-BN; 50% of the patients had HIV and were virally suppressed.

“These data support public health messaging around behavior modification and risk reduction counseling in the immediate postvaccination period,” the authors write.


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Abstract/Full Text

Predictors of Weight Gain, Metabolic Complications in Patients With HIV on Antiretroviral Therapy

HIV
Additional studies are needed to evaluate the effects of different antiretroviral therapy regimens on weight gain and other metabolic comorbidities. Credit: Getty Images

Veterans with HIV infection were found to have lower rates of obesity overall compared with age-matched HIV-negative individuals. For patients with HIV infection, significant increases in weight were primarily observed within the first 2 years of antiretroviral therapy (ART) initiation and among those with lower BMI at diagnosis. These study findings were published in HIV Medicine.

Researchers at the Michael E DeBakey Veterans Affairs (VA) Medical Center in the United States sourced data for this study from the VA corporate data warehouse. Between 2000 and 2015, patients with HIV infection (n=22,421) were matched by age against those without HIV infection (controls; n=63,072) and evaluated to identify factors associated with changes in body weight. The researchers assessed patients’ body weight at baseline in comparison with years 1, 2, and 5 following HIV diagnosis (baseline visit for control patients), respectively.

Among patients in HIV and control groups, 96.7% and 96.3% were men (P <.01), 54.7% and 46.8% were younger than 50 years (P <.01), 51.1% and 18.1% were Black (P <.01), 47.2% and 19.6% had a baseline BMI of less than 25 kg/m2 (P <.01), 16.8% and 25.4% had diabetes (P <.01), and 61.9% and 69.8% had hypertension (P <.01), respectively. After 5-years of follow up, the study groups comprised 14,156 HIV-positive and 36,993 HIV-negative patients.

Researchers evaluated ART regimens among patients in the HIV group between baseline and year 1. Results showed that 55.2% of patients used nucleoside reverse transcriptase inhibitors (NRTIs) plus non-NRTIs (NNRTIs), 37.3% used NRTIs plus protease inhibitors (PIs), 6.40% used NRTIs plus integrase strand transfer inhibitors (INSTIs), and 1.07% used NRTIs plus other agents. After 5 years, the rate of patients receiving NRTIs plus NNRTIs (57.1%) or NRTIs plus PIs (40.5%) increased, and the rate of patients receiving NRTIs plus INSTIs (1.6%) or NRTIs plus other agents (0.86%) decreased.


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Between baseline and years 1, 2, and 5, significantly more weight loss was observed among patients in the HIV group who were not receiving ART vs those in the control group (all P <.01). Further analysis of this time period showed that significantly more weight loss occurred among patients aged between 50 and 59 years vs those younger than 50 years (all P <.01), with similar results observed among those 60 years and older vs those younger than 50 years (all P <.01). Significant increases in weight were observed among patients in the HIV group receiving ART vs those in the control group (P <.01 for years 1 and 2; P =.03 for year 5), as well as among those of Black vs White ethnicity (P <.01 for years 1 and 5; P =.05 for year 2).

Among patients in the HIV group receiving ART, predictors for weight loss at all 3 time points included being aged 50 years and older (all P <.01), a BMI between 25 and 29 vs 30 kg/m2 or higher (all P <.01), a BMI of 30 or higher vs lower than 25 kg/m2 (all P <.01), and a CD4+ count higher than 200 vs 200 or lower cells/mm2 (all P <.01). Predictors for weight gain at all 3 time points included receipt of NRTIs plus INSTIs vs NRTIs plus NNRTIs (all P <.01), HIV virologic suppression of more than 80% (all P <.01), and Black vs White ethnicity (P <.01 for years 1 and 2; P =.02 for year 5).

The most significant predictor for weight loss was a CD4+ count of more than 200 cells/mm2, which contributed to an estimated weight loss of -5.62 kg at year 1 (P <.01), -3.11 kg at year 2 (P <.01), and -0.95 kg at year 5 (P <.01).

Limitations include the retrospective design, the inability to adjust for changes in patients’ ART regimens, and the inability to match patients by race.

According to the researchers, “the findings from this study also demonstrate an interplay between an individual’s predisposition to obesity, viral factors, ART, and the environment.”

Reference

Garcia JM, Dong Y, Richardson P, et al. Effect of HIV and antiretroviral therapy use on body weight changes in a cohort of US veterans living with and without HIV. HIV Med. Published online August 5, 2022. doi:10.1111/hiv.13366

This article originally appeared on Infectious Disease Advisor

HPV Vaccination, Infection Rates Examined in US Women

The researchers found that the prevalence of HPV-16/18 among participants born in the 1990s was statistically significantly lower (5.6%) than among those born in the 1980s (12.5%). Credit: Getty Images.

HealthDay News — Human papillomavirus (HPV) vaccination appears to be associated with a reduction in HPV-16/18 infection prevalence among a recent birth cohort of vaccinated and unvaccinated 18- to 26-year-old women, according to a research letter published in JAMA Health Forum.

Zahed Shahmoradi, PhD, from the University of Texas Health Science Center in Houston, and colleagues compared HPV prevalence in 1980s and 1990s birth cohorts to assess whether HPV vaccination has been associated with reduced infection rates among 18- to 26-year-old age groups. The analysis included data from 2 cycles (2005 to 2006 and 2015 to 2016) of the US National Health and Nutrition Examination Survey (2698 women).

The researchers found that the prevalence of HPV-16/18 among participants born in the 1990s was statistically significantly lower (5.6%) than among those born in the 1980s (12.5%). HPV-16/18 prevalence among women aged 18 to 26 years old was 15.2% before vaccination introduction (2005 to 2006 cycle) and declined to 3.3% overall (5.1% among unvaccinated and 1% among vaccinated groups) in the 2015 to 2016 period. During the 2015 to 2016 cycle compared with the 2005 to 2006 cycle, the estimated probability of HPV-16/18 infection was 78% lower overall, including 60 percent lower for the unvaccinated and 92 percent lower for the vaccinated.

“A larger decline in the prevalence of HPV-16/18 infection among 18- to 20-year-old women during the 2015 to 2016 time period may reflect greater direct and herd protection from broader HPV vaccination coverage,” the authors write.


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One author disclosed financial ties to the pharmaceutical industry.

Abstract/Full Text

PA Program Creates LGBTQ+ Training Workshop

LGBTQ+ Flag
“Graduating PAs need to be confident and prepared to treat transgender patients that they will encounter in the many specialties that they enter,” said Gina Pontrelli, DHSc, PA-C Credit: Getty Images

A training class to better prepare PA students to care for the unique needs of members of the LGBTQ+ community is available at the Hofstra Northwell School of Nursing and Physician Assistant Studies. Preliminary outcomes data show that the program significantly increased knowledge among PA students that was sustained over time.  

“Graduating PAs need to be confident and prepared to treat transgender patients that they will encounter in the many specialties that they enter,” said Gina Pontrelli, DHSc, PA-C, who is assistant professor at Hofstra Northwell School of Nursing and Physician Assistant Studies. “Re-evaluating the curriculum to provide focused training of PAs to better prepare them for transgender care is likely to have a much-needed significant and positive impact on the health and welfare of the transgender community.” The training course was developed by Dr Pontrelli and Amy Roberts, PhD, PA-C, who is also assistant professor at the Hofstra PA program, with assistance from Denise Rizzolo, PhD, MPH, PA-C, of the Physician Assistant Education Association. 

In 2021, the program was integrated into an existing didactic PA course, which was restructured to provide high-impact learning modules and assessments designed to refine the care the LGBTQ+ community receive, Dr Pontrelli said.

Gina Pontrelli, DHSc, PA-C
Gina Pontrelli, DHSc, PA-C

“Instruction was delivered longitudinally throughout the course and encompassed small group activities and problem-based learning facilitated by an LGBTQIA+ panel comprised of individuals spanning the gender spectrum,” Dr Pontrelli said in an interview. “Faculty collaborated with standardized patient educators in the case development process and small group learning sessions. Faculty also defined objectives for the course activities.”


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“Students were given clinical cases focused on the progressive development of communication skills in inclusive sexual history taking, counseling, and debriefing performed by panel experts and data-driven materials. The module consisted of 3 sessions, which are 4 hours long, that are delivered during the final didactic semester before students started their clerkship.

Outcomes Data

Students at Hofstra PA program were surveyed on their comfort level providing health care to transgender patients before and immediately after going through the program as well as at 2 and 4 months after completing the program. The results showed a significant positive change in students being able to:

  • Articulate the unique health needs of LGBTQ+ individuals
  • Recommend primary care, anticipatory guidance, and health care maintenance
  • Identify unique resources available to support the health and wellness of LGBTQ+ individuals

Based on the results, the training course will be offered each year to PA students. The initiative is funded by Hofstra’s LGBTQ+ Research Initiative Grant.

Members of the LGBTQ+ community, specifically transgender people, experience mental illness, HIV, sexually transmitted diseases, and physical and sexual violence at higher rates than cisgender individuals. Despite this there are significant disparities in health care delivery to LGBTQ+ due to social, economic, and medical infrastructure as well as a lack of health care providers that are both knowledgeable and compassionate towards this population.

Source

PA studies creates new LGBTQ+ training workshop. News Release. Hofstra University. April 25, 2022. Accessed September 12, 2022. https://news.hofstra.edu/2022/04/25/pa-studies-creates-new-lgbtq-training-workshop/

Many Preventive Medical Services Cost Patients Nothing. Will a Texas Court Decision Change That?

Under a provision of the ACA that went into effect in late 2010, many services considered preventive are covered without a copayment or deductible from the patient. Credit: Getty Images.

A federal judge’s ruling in Texas has thrown into question whether millions of insured Americans will continue to receive some preventive medical services, such as cancer screenings and drugs that protect people from HIV infection, without making a copayment.

It’s the latest legal battle over the Affordable Care Act, and Wednesday’s ruling is almost certain to be appealed.

A key part of the ruling by Judge Reed O’Connor of the US District Court for the Northern District of Texas says 1 way that preventive services are selected for the no-cost coverage is unconstitutional. Another portion of his ruling says a requirement that an HIV prevention drug therapy be covered without any cost to patients violates the religious freedom of an employer who is a plaintiff in the case.

It is not yet clear what all this means for insured patients. A lot depends on what happens next.


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O’Connor is likely familiar to people who have followed the legal battles over the ACA, which became law in 2010. In  2018, he ruled that the entire ACA was unconstitutional. For this latest case, he has asked both sides to outline their positions on what should come next in filings due September 16.

After that, the judge may make clear how broadly he will apply the ruling. O’Connor, whose 2018 ruling was later reversed by the US Supreme Court, has some choices. He could say the decision affects only the conservative plaintiffs who filed the lawsuit, expand it to all Texans, or expand it to every insured person in the US He also might temporarily block the decision while any appeals, which are expected, are considered.

“It’s quite significant if his ruling stands,” said Katie Keith, JD, director of the Health Policy and the Law Initiative at the O’Neill Institute for National and Global Health Law at the Georgetown University Law Center.

We asked experts to weigh in on some questions about what the ruling might mean.

What does the ACA require on preventive care?

Under a provision of the ACA that went into effect in late 2010, many services considered preventive are covered without a copayment or deductible from the patient.

recent estimate from the US Department of Health and Human Services found that more than 150 million people with insurance had access to such free care in 2020.

The federal government currently lists 22 broad categories of coverage for adults, an additional 27 for women, and 29 for children.

To get on those lists, vaccines, screening tests, drugs, and services must have been recommended by 1 of 3 groups of medical experts. But the ruling in the Texas case centers on recommendations from only 1 group: the US Preventive Services Task Force, a nongovernmental advisory panel whose volunteer experts weigh the pros and cons of screening tests and preventive treatments.

Procedures that get an “A” or “B” recommendation from the task force must be covered without cost to the insured patient and include a variety of cancer screenings, such as colonoscopies and mammograms; cholesterol drugs for some patients; and screenings for diabetes, depression, and sexually transmitted diseases.

Why didn’t the ACA simply spell out what should be covered for free?

“As a policymaker, you do not want to set forth lists in statutes,” said Christopher Condeluci, a health policy attorney who served as tax and benefits counsel to the US Senate Finance Committee during the drafting of the ACA. One reason, he said, is that if Congress wrote its own lists, lawmakers would be “getting lobbied in every single forthcoming year by groups wanting to get on that list.”

Putting it in an independent body theoretically insulated such decisions from political influence and lobbying, he and other experts said.

What did the judge say?

It’s complicated, but the judge basically said that using the task force recommendations to compel insurers or employers to offer the free services violates the Constitution.

O’Connor wrote that members of the task force, which is convened by a federal health agency, are actually “officers of the United States” and should therefore be appointed by the president and confirmed by the Senate.

The decision does not affect recommendations made by the other 2 groups of medical experts: the Advisory Committee on Immunization Practices, which makes recommendations to the Centers for Disease Control and Prevention on vaccinations, and the Health Resources and Services Administration, a part of the Department of Health and Human Services that has set free coverage rules for services aimed mainly at infants, children, and women, including birth control directives.

Many of the task force’s recommendations are noncontroversial, but a few have elicited an outcry from some employers, including the plaintiffs in the lawsuit. They argue they should not be forced to pay for services or treatment they disagree with, such as HIV prevention drugs.

Part of O’Connor’s ruling addressed that issue separately, agreeing with the position taken by plaintiff Braidwood Management, a Christian, for-profit corporation owned by Steven Hotze, a conservative activist who has brought other challenges to the ACA and to coronavirus mask mandates. Hotze challenged the requirement to provide free coverage of preexposure prophylaxis (PrEP) drugs that prevent HIV. He said it runs afoul of his religious beliefs, including making him “complicit in facilitating homosexual behavior, drug use, and sexual activity outside of marriage between 1 man and 1 woman,” according to the ruling.

O’Connor said forcing Braidwood to provide such free care in its insurance plan, which it funds itself, violates the federal Religious Freedom Restoration Act.

What about no-copay contraceptives, vaccines, and other items that are covered under recommendations from other groups not targeted by the judge’s ruling?

The judge said recommendations or requirements from the other 2 groups do not violate the Constitution, but he asked both parties to discuss the ACA’s contraceptive mandate in their upcoming filings. Currently, the law requires most forms of birth control to be offered to enrollees without a copayment or deductible, although courts have carved out exceptions for religious-based employers and “closely held businesses” whose owners have strong religious objections.

The case is likely to be appealed to the fifth US Circuit Court of Appeals.

“We will have a conservative court looking at that,” said Sabrina Corlette, JD, co-director of Georgetown University’s Center on Health Insurance Reforms. “So I would not say that the vaccines and the women’s health items are totally safe.”

Does this mean my mammogram or HIV treatment won’t be covered without a copayment anymore?

Experts say the decision probably won’t have an immediate effect, partly because appeals are likely and they could continue for months or even years.

Still, if the ruling is upheld by an appellate court or not put on hold while being appealed, “the question for insurers and employers will come up on whether they should make changes for 2023,” said Keith.

Widespread changes next year are unlikely, however, because many insurers and employers have already drawn up their coverage rules and set their rates. And many employers, who backed the idea of allowing the task force to make the recommendations when the ACA was being drafted, might not make substantial changes even if the ruling is upheld on appeal.

“I just don’t see employers for most part really imposing copays for stuff they believe is actually preventive in nature,” said James Gelfand, JD, president of the ERISA Industry Committee, which represents large, self-insured employers.

For the most part, Gelfand said, employers are in broad agreement on the preventive services, although he noted that covering every type or brand of contraceptive without a patient copayment is controversial and that some employers have cited religious objections to covering some services, including the HIV preventive medications.

Religious objections aside, future decisions may have financial consequences. As insurers or employers look for ways to hold down costs, they might reinstitute copayments or deductibles for some of the more expensive preventive services, such as colonoscopies or HIV drugs.

“With some of the higher-ticket items, we could see some plans start cost sharing,” said Corlette.

KHN (Kaiser Health News) is a national newsroom that produces in-depth journalism about health issues. Together with Policy Analysis and Polling, KHN is one of the three major operating programs at KFF (Kaiser Family Foundation). KFF is an endowed nonprofit organization providing information on health issues to the nation.

Newly Minted PAs Ready to Tackle Health Disparities

health care disparities
“PAs are a major part of the solution to improve access to care, meet the increasing demand for high-quality providers, and address issues pertaining to health care disparities in patients with chronic conditions,” said Dr Orozco. Credit: Getty Images

New data shows that the PA profession is growing by leaps and bounds with the number of newly certified PAs reaching a record high of 10,950 in 2021. With nearly 160,000 PAs in practice and numbers projected to increase by 31% between 2020 and 2030, it is hard to understand how the gaps in health care access remain. We spoke with American Academy of Physician Associates (AAPA) President and Chair of the Board Jennifer M. Orozco, DMSc, PA-C, DFAAPA, to better understand the PA professional landscape and what can be done to help PAs better tackle health care disparities.

Dr Orozco is also director of Advanced Practice Providers at Rush University Medical Center in Chicago and assistant professor in the Department of PA Studies at Rush University College of Health Sciences.

Q: What is underlying the marked gaps in health care access and health disparities in the US?

Jennifer Orozco AAPA 2022
Jennifer M. Orozco, DMSc, PA-C, DFAAPA

Dr Orozco: The reality is that patient needs are outpacing provider supply. We know that 96 million Americans lack adequate access to primary care and less than half of those with access are actually having their needs met. We have 155 million Americans without access to mental health care. We have an aging population projected to reach almost 95 million by 2060. And approximately 42% of adults over the age of 20 years are obese and many have obesity-related conditions such as heart disease, stroke, type 2 diabetes, and certain types of cancer.

We have had a mass exodus in the health care workforce across the country and now face a projected workforce shortage of 3.2 million health care workers by 2026. In rural areas, the gaps in access may be even wider. However, findings from a JAMA study showed a 49.3% increase in the density of PAs in rural counties between 2009 and 2017 compared with a 14% increase among physicians in these areas. PAs can help improve access to care, especially given that the profession is projected to grow 31% between 2020 and 2030. However, we are not utilizing PAs as best as we should due to outdated legislation that prevents PAs from practicing to the full extent of their education and training.


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Credit: Health Resources & Services Administration

Q: Can you give an example of how PAs are not used to the fullest extent of their training?

Dr Orozco: A colleague of mine practices in a rural part of Southeast Colorado, which recently experienced a large turnover among all health care providers. She’s worked as a PA there for nearly 20 years providing preventative HIV treatment, hepatitis treatment, and long-acting contraceptives among other services. Her supervising physician left and the new physician who was hired does not specialize in infectious disease or gynecologic care. Because these areas are not in the physician’s scope of practice, the PA is now no longer allowed to perform these services. She has to send her patients — whom she has been caring for for years — hours away to access care.

This is one example of how deep-seated in tradition we are in medicine; we can’t let go of things that don’t make sense anymore. At Rush, we discuss how we need to push the status quo and bring everyone along with us. I have this same philosophy at AAPA. Many people can deliver health care, whether they are a PA, a nurse, nurse practitioner (NP),  or physical therapist; we have to start being innovative in health care delivery in order to meet the needs of our patients.

Q: What can clinicians do to help lobby for legislative change?

Dr Orozco: I think it is about building relationships — not just with legislators and policy makers, but with all stakeholders in a modern health care delivery system — and chipping away [at the status quo] to make a difference. Talk to people who will listen and keep pushing where you can. Always keep the discussion patient-focused because they are the ones who suffer if we can’t enact change.

Q: The recently released NCCPA survey showed a record number of PAs entering the field in 2021. What is attracting people to become PAs?

Dr Orozco: The pandemic heightened the need for more health care providers, but even prior to that, the PA profession was highly sought after. For the fifth year in a row, PA was named one of the top 2 health care jobs in the country by US News & World Report in its annual Best Jobs List. In this day and age, especially across generations, people really want to get into health care to serve patients. All of the evidence that we have gathered over the years on how PAs practice, are trained, and the high quality of care that they deliver is attracting people to become PAs.

Q: Did any data on practice patterns from the NCCPA survey surprise you?

Dr Orozco: I wasn’t surprised by many of the statistics as they align with the shifts we are seeing in health care, which is a good sign. The survey showed this continuing shift from inpatient management to ambulatory care. From a health care system perspective, we started to focus on ambulatory footprint expansion, particularly with the rise of telemedicine during the pandemic.

Q: What else would you like to tell Clinical Advisor readers?

Dr Orozco: The biggest take-home message is that PAs are a major part of the solution to improve access to care, meet the increasing demand for high-quality providers, and address issues pertaining to health care disparities in patients with chronic conditions. We will never have enough PAs, physicians, NPs, or nurses to meet patient demand. Yet, we have this untapped supply of 160,000 highly-trained PAs who have completed one of the most rigorous medical education models yet are not being optimally utilized. The continued growth in the PA profession is tremendous. At AAPA, I continue to focus on elevating awareness about how PAs go beyond for their patients every day, and why it is so important that we remove archaic and outdated barriers so that we can continue to provide all patients the care they deserve.

We have to modernize health care delivery. The old way hasn’t worked for a long time and the pandemic has heightened the need for change. PAs are highly educated and trained and able to take care of complex patients. The PA profession is continuing to grow and is here to help improve access in this country and provide high-quality care for patients.

USPSTF Continues to Recommend Against Genital Herpes Screening

genital herpes screening recommendation
No new evidence found to change to the 2016 recommendation against routine screening for genital herpes. Credit: CDC/Joe Miller

HealthDay News — The US Preventive Services Task Force (USPSTF) did not find new evidence that could result in a change to the 2016 recommendation on screening for genital herpes and consequently continues to recommend against routine serologic screening, according to a draft recommendation statement published online.

Gary N. Asher, MD, MPH, from RTI International-University of North Carolina at Chapel Hill Evidence-based Practice Center in Research Triangle Park, and colleagues dually reviewed 3119 abstracts and 64 full-text articles against a priori eligibility criteria to identify evidence that could result in a change in the 2016 USPSTF D recommendation for herpes simplex virus 2 (HSV-2) screening. The researchers did not identify any new eligible studies on the benefits or harms of HSV-2 serologic screening, accuracy of available HSV-2 serologic tests, or preventive interventions that could be used in asymptomatic individuals who are seropositive for HSV-2 to reduce morbidity and transmission of genital herpes. Foundational evidence that informed the 2016 recommendation indicated a high-rate of false-positive test results and potential psychosocial harms associated with serologic screening for genital herpes.

Based on these findings, the USPSTF continues to recommend against routine serologic screening for genital herpes simplex virus infection in asymptomatic adolescents and adults, including pregnant persons (D recommendation).

The draft recommendation statement and draft evidence review have been published for public comment. Comments can be submitted from August 16 to September 12, 2022.


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Draft Evidence Review

Draft Recommendation Statement

Comment on Recommendation Statement

Human papillomavirus in males

 Each month, The Clinical Advisor makes one new clinical feature available ahead of print. Don’t forget to take the poll. The results will be published in the next month’s issue.

The efforts of the healthcare community to promote female human papillomavirus (HPV) vaccination and reduce the incidence of cervical cancer have overshadowed the importance of male HPV immunization. A need for greater emphasis on promoting male vaccination for HPV was magnified through the recent results of the 2013-2014 National Health and Nutrition Examination Survey (NHANES), which brought to light the importance of protecting males against HPV.1 In a subset of 1,868 men, the overall genital HPV infection prevalence was 45.2%, and the high-risk oncogenic HPV prevalence was 29.5%.1 Per NHANES, the oral HPV infection rate among males is 11.5%, which translates to 11 million men and is three times the prevalence rate of female oral HPV infection.2 The Centers for Disease Control (CDC) estimates that 74% of the 19.7 million new sexually transmitted infections in the United States each year are HPV infections.3

HPV and associated cancers

Eight HPV genotypes—HPV 16, 18, 31, 33, 35, 45, 52, and 58—have been identified as oncogenic; that is, these genotypes have an increased risk of mutating into cancer.4 HPV 16 and 18 are the genotypes most commonly associated with the development of anal, oropharyngeal, penile, cervical, vaginal, and vulvar cancers.5 Although all cases of HPV exposure and infection do not result in cancer development, the HPV vaccine series provides hope for significant long-term reduction of HPV-related cancer incidence among males and females.


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For optimal vaccine effectiveness, HPV immunization should be offered to all adolescents at age 11 or 12 years or before the onset of sexual intimacy.6 The most recent estimates show that 42% of adolescent boys have received one or more doses of the HPV vaccine, an increase of 8% from the 2013 National Immunization Survey–Teen estimates for boys.7 These statistics reflect a very gradual increase in HPV vaccine uptake. However, it is notable that with currently fewer than 50% of males being vaccinated, a segment of the male population annually ages out of the recommended age vaccine cohort but remains at risk for exposure and uptake of all HPV genotypes.

Current data suggest that HPV infection rates in young males may range from 45% to 93% when both low- and high-risk populations are considered.8 The importance of recommending male vaccination cannot be overemphasized, because the risk of male-to-female HPV transmission is significant. A recent meta-analysis examining HPV concordance among heterosexual couples indicated that HPV is more readily transmissible from infected males to females than the reverse.9

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Quadrivalent HPV Vaccine Less Effective in Immunocompromised Youth

Doctor administering vaccine
Antibody titers to the HPV4 vaccine were lower for all HPV serotypes in individuals who were infected with HIV perinatally than those who were exposed to HIV perinatally.

Antibody titers to the quadrivalent HPV (HPV4) vaccine were lower for all HPV serotypes (6, 11, 16, and 18) in individuals who were infected with HIV perinatally than in individuals who were exposed to HIV perinatally, but uninfected, according to study results published in Clinical Infectious Diseases.

In clinical trials, the efficacy of the HPV4 vaccine from Merck & Co. reached nearly 100%. Further, population-based studies from national registries have suggested that this HPV vaccine has already had an effect in vaccinated youth age 11 to 14 years. However, antibody durability and efficacy in populations that are immunocompromised, like perinatally exposed youths with HIV, is not as well understood. In addition, HIV infection increases the risk for HPV-associated cancer development. However, antibody titer data for perinatally exposed youths with HIV receiving less than 3 doses is limited and there is no published HPV vaccine efficacy data available for perinatally exposed youths with HIV of any age. Therefore, this prospective observational cohort study compared antibody titers with HPV 6, 11, 16, and 18 and the rate of abnormal cytology between perinatally exposed youths with HIV who received the HPV4 vaccine and perinatally exposed youth without HIV.

This study was performed as part of the multicenter Pediatric HIV/AIDS Cohort Study Adolescent Master Protocol. Antibody titer data were available for 310 perinatally exposed youths with HIV and 148 perinatally exposed youth without HIV. When compared with the perinatally exposed youth without HIV, the perinatally exposed youths with HIV had better HPV vaccine coverage with only 10% unvaccinated compared with 22%. Further, 40% of the perinatally exposed youths with HIV and 16% of the perinatally exposed youth without HIV received at least 2 vaccine doses, with females being more likely to receive 3 doses in both populations. Rates of abnormal cervical cytology and genital warts were included in vaccine effectiveness determination. Seroconversion and geometric mean titer against HPV types 6, 11, 16, and 18 were calculated.

Results showed that antibody titers to HPV4 were lower for all serotypes in perinatally exposed youths with HIV compared with perinatally exposed youth without HIV. Seroconversion to HPV 6, 11, 16, and 18 occurred in 83%, 84%, 90%, and 62%, respectively, of vaccinated perinatally exposed youths with HIV (n=310) compared with 94%, 96%, 99%, and 87%, respectively, in vaccinated perinatally exposed youth without HIV (n=148), (P <.05). While geometric mean titers were lower in each category of HPV4 doses received in perinatally exposed youths with HIV compared with perinatally exposed youth without HIV, higher geometric mean titers were associated with younger age, lower HIV type 1 RNA viral load, and higher CD4% at first HPV4 vaccination. However, the most striking result was the high rate of abnormal cytology in perinatally exposed female youths with HIV, regardless of the number of HPV4 vaccine doses received or timing of doses relative to sexual debut. Abnormal cytology occurred in 33 of 56 perinatally exposed youths with HIV and 1 of 7 perinatally exposed female youth without HIV who were vaccinated and were sexually active, which yielded incidence rates (per 100 person-years) of 15.0 and 2.9, respectively.


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Overall, the study authors concluded that, “[T]he association between level of immunosuppression and lower [geometric mean titers], as well as observed reduced effectiveness, suggests that [perinatally exposed youths with HIV] children vaccinated at a time of immunosuppression should be revaccinated when immunocompetent.”

Reference

Moscicki AB, Karalius B, Tassiopoulos K, et al. Human papillomavirus antibody levels and quadrivalent vaccine clinical effectiveness in perinatally human immunodeficiency virus- infected and exposed, uninfected youth [publishing online February 21, 2019]. Clin Infec Dis. doi:10.1093/cid/ciy1040

This article originally appeared on Infectious Disease Advisor

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