Revisiting HIV-Associated Wasting: Results from a U.S. Cross-Sectional Survey of Health Care Providers’ Knowledge,Attitude,and Current Practices

Abstract

Advancements in antiretroviral therapy (ART) have significantly improved morbidity and mortality rates among people with human immunodeficiency virus (HIV) (PWH), leading to prolonged survival, and many are now living into middle and old age. However, this population now faces aging-related comorbidities, including cachexia HIV-associated wasting (HIVAW), which remains inadequately addressed in the context of contemporary ART. Effective management of HIVAW requires a multifaceted approach that targets underlying causes while addressing coexisting health conditions. Currently, recombinant human growth hormone (rhGH) (somatropin) is the only FDA-approved treatment for HIVAW that increases body weight and lean body mass and improves physical endurance. However, the lack of standardized definitions and clear treatment guidelines may contribute to the underdiagnosis and suboptimal management of HIVAW. This study aimed to assess health care providers’ (HCPs) knowledge, attitudes, and contemporary clinical practices regarding HIVAW through a cross-sectional survey conducted in collaboration with the American Academy of HIV Medicine. Approximately half of the respondents recognized a 3% prevalence rate of HIVAW, noting its association with increased morbidity and health care resource utilization. However, nearly one-third faced challenges in diagnosing HIVAW due to unclear definitions, highlighting the need for standardized clinical guidelines. Less experienced providers demonstrated less familiarity with treatment options like rhGH compared to their more experienced colleagues. While 88.4% identified nutritional supplements as a management strategy, only 32.2% were aware of an FDA-approved treatment for HIVAW, indicating a substantial knowledge gap. This study underscores the need for enhanced educational initiatives and clear treatment guidelines to improve the recognition and management of HIVAW, particularly among less experienced HCPs.

Keywords

antiretroviral therapy comorbidity cross-sectional survey human immunodeficiency virus mortality wasting unintentional weight loss cachexia

Introduction

Advancements in the management of human immunodeficiency virus (HIV), particularly with antiretroviral therapy (ART), have significantly improved the morbidity and mortality of people with HIV (PWH).^1–3 As a result, PWH have increased survival; however, they experience aging-related comorbidities, including HIV-associated wasting (HIVAW).^4,5

In the era of modern ART, the clinical presentation of HIVAW extends from overt cachexia to sarcopenic obesity, affecting an estimated 25%–30% of aging PWH and becoming more prevalent than traditional wasting. The frequent under-recognition of this hidden muscle loss may likely explain why many providers report not encountering HIVAW even as patients continue to experience decline in physical function and frailty.^6,7

This condition has received inadequate attention in the context of modern ART.^5,8 Recent real-world evidence indicates that annually, approximately 3.1% of patients receiving medical care for HIV meet the criteria for HIVAW.⁸ Individuals with HIVAW are at a greater risk of hospitalization, use more health care resources, and present with a higher burden of comorbidities than their non-HIVAW counterparts.^8,9

The clinical management of HIVAW requires a multifaceted approach that addresses the underlying causes of wasting while treating concurrent conditions. Therapeutic interventions are developed based on the individual needs of patients. Currently, recombinant human growth hormone (somatropin) is the only FDA-approved treatment for HIVAW, which increases body weight, lean body mass and improves physical endurance.^10,11

The absence of a standardized definition for HIVAW and the lack of well-defined treatment guidelines may contribute to clinicians neglecting the diagnosis and management of HIVAW, along with instances of unintentional weight loss.^3,12

The clinical presentation of HIVAW has evolved over time, with wasting and weight loss occurring less frequently and with diminished severity after the introduction of ART.^13,14

To date, no studies have comprehensively investigated awareness of attitudinal determinants impeding clinicians from promptly identifying and treating wasting and unintentional weight loss in this patient population. This study aimed to investigate the knowledge, attitudes, and empirical observations of health care providers (HCPs) directly involved in HIV care regarding HIVAW and unintentional weight loss within the current clinical landscape in the United States.

Materials and Methods

Study design and survey methodology

This noninterventional, cross-sectional survey was conducted between April and June 2024 in collaboration with the American Academy of HIV Medicine (AAHIVM) (Supplementary Data S1). The survey involved the administration of a formatted and standardized questionnaire comprising 30 predefined multiple-choice and open-ended questions and select-all-that-apply questions. The AAHIVM distributed the questionnaire to its members and credentialed providers via email, including to over 3,000 HCPs who were providers of direct care to PWH across the United States. Participation in the survey was voluntary, and consent was obtained. The survey was open for 3 months. A response rate of 10%–12% was estimated, resulting in an anticipated sample size of 300–360 respondents. The completion of the anonymous web-based survey served as informed consent documentation.

Objectives and outcomes

The primary objective of this study was to understand the knowledge gaps among HCPs regarding HIVAW prevalence, incidence, and detection based on the responses collected in the survey. The secondary objectives were to examine the current practices in managing patients with HIVAW and unintentional weight loss, capturing HCPs’ self-reported treatment behaviors and challenges they face in this context. Further, the impact of variability among HCPs regarding their knowledge and attitudes, considering their demographics, training, and overall experience, was assessed.

Participants

The study population comprised U.S.-based HCPs who were actively engaged in the direct care of PWH. Eligible participants included a broad range of clinicians, including medical doctors (MDs and DOs), nurse practitioners, physician assistants, doctors of nursing practice, and pharmacists. Providers were contacted through AAHIVM’s professional network, ensuring a representative sample of frontline HIV-care professionals from diverse geographic locations and practice settings (urban, rural, and suburban). There were no stringent exclusion criteria apart from non-practicing clinicians and those not based in the United States.

Ethical considerations

The study was submitted to the Advarra^® institutional review board (IRB) for review, with a request for an exemption according to the criteria for an anonymous survey that contained no identifying factors. The study qualified for IRB-exempt review under 45 CFR 46.104(d)(3). The invitation to participate included a statement indicating that following the study link and completing the survey constituted informed consent.

Statistical analyses

All collected data were descriptively presented, highlighting categorical variables. The total number of respondents and the corresponding percentage for each response were systematically reported for each survey question. Missing data were addressed by including all non-missing responses, with no imputation for missing data. To evaluate the temporal evolution of HIVAW diagnosis and treatment, respondents’ years of experience were categorized into three distinct groups: ≤10 years (practicing since 2014), 11–20 years (practicing since 2004), and ≥21 years (practicing pre-2004).

Contingency tables were created to conduct comparative analyses of responses across these categories, and Fisher’s exact test was used to assess statistical significance. The sample size was determined by feasibility and aimed to capture responses from a wide cross-section of the HIV-care provider community rather than by formal hypothesis-driven power calculations. All analyses were performed using R Statistical Software (version 4.2.2; R Core Team 2021).

Results

Study sample and demographics

A total of 446 respondents were assessed for eligibility; of these, 101 (22.6%) did not progress beyond the initial question, “Are you a healthcare provider currently practicing medicine in the United States?” Overall, 345 (77.4%) respondents answered at least four survey questions and were considered responders. Among them, 265 (76.8%) provided complete responses, including demographic data, and were categorized as completers, whereas 80 (23.2%) chose not to disclose demographic information.

The majority (67.2%) of completers were aged <45 years, and 67.9% were treating patients in an urban practice. In addition, 57.7% identified as White and 13.2% as Hispanic or Latino/Latina. Overall, 66.4% of completers reported treating patients with HIV for up to 10 years, and 72.8% indicated they do not expect to retire within the next decade. HCP demographics are summarized in (Table 1).

Table 1.

Demographic Characteristics of Completers (N = 265)

Variable	Category	N (%)
Age, years	25–34	85 (32.1)
	35–44	93 (35.1)
	45–54	44 (16.6)
	55–64	31 (11.7)
	65 or older	12 (4.5)
Race	White	153 (57.7)
	Asian or Asian American	49 (18.5)
	Black or African American	29 (10.9)
	Hispanic or Latino/Latina	35 (13.2)
	Middle Eastern or North African	4 (1.5)
	American Indian or Alaska Native	1 (0.5)
	Multi-racial	12 (4.5)
	Other	14 (5.3)
	Not reported	3 (1.1)
Location of practice	Urban	180 (67.9)
	Suburban	64 (24.2)
	Rural	21 (7.9)
Degrees and professional affiliations^a	MD	86 (30.1)
	DO	8 (2.8)
	DNP	12 (4.2)
	NP	51 (17.8)
	PA	26 (9.1)
Postnominal affiliations^a,b	AAHIVS	127 (37.1)
	AAHIVP	74 (21.6)
	FAAFP	9 (2.6)
	DABFM	9 (2.6)
	FACE	1 (0.3)
	FACP	12 (3.5)
	MPH	26 (7.6)
	PhD	1 (0.3)
	DHSc/DHS	3 (0.9)
	None	54 (15.8)
	Other	26 (7.6)
Years treating PWH	≤10 years	176 (66.4%)
	11–20 years	50 (18.8%)
	>20 years	39 (14.7%)
Number of PWH treated per week	1–5	66 (24.9%)
	6–15	62 (23.4%)
	16–25	36 (13.6%)
	26–35	21 (7.9%)
	36–45	23 (8.7%)
	46–55	21 (7.9%)
	56+	62 (23.4%)
Years until retiring from HIV practice	In less than 2 years	17 (6.4%)
	3 to 5 years	16 (6.0%)
	5 to 10 years	39 (14.7%)
	11 years or more	193 (72.8%)

Respondents could choose all that apply, % is of all responses.

No one chose Fellow, American College of Cardiologists (FACC) or Registered Dietitian/Nutritionists (RD/RDN).

AAHIVS, American Academy of HIV Medicine Specialist; AAHIVP, American Academy of HIV Medicine Pharmacist; DABFM, Diplomat American Board of Family Medicine; DHSc/DHS, Doctorate of Health Science; DO, doctor of osteopathy; DNP, doctor of nursing practice; FAAFP, Fellow, American Academy of Family Practitioners; FACE, Fellow American College of Endocrinology; FACP, Fellow, American College of Physicians; MPH, Master of Public Health; PhD, Doctorate of Philosophy MD, Medical doctor; NP, nurse practitioner; PA, physician assistant; PharmD, pharmacy doctor.

To analyze whether the treatment of PWH experiencing unintentional weight loss or wasting has evolved over time, the number of years of treating patients was categorized into three groups (Table 2). The analysis revealed no significant differences among these groups, stratified by years of treating patients with HIV, with respect to race, ethnicity, or practice location. As expected, associations were observed between years of treating patients with HIV and time-related variables, specifically age and years until anticipated retirement.

Table 2.

Time Categories of HCPs Based on Years of Experience Treating Patients with HIV

Years treating patients with HIV (years)	Completers n = 265, n (%)	Treatment era-3 categories	Years treating HIV patients, (years)	Completers N = 265, n (%)	Treatment era—2 categories	Years treating patients with HIV (years)	Completers n = 265, n (%)
1–5	117 (44.2)	2014 to present	≤10	176 (66.4)	2014 to present	≤10	176 (66.4)
6–10	59 (22.3)	2014 to present	≤10	176 (66.4)	2014 to present	≤10	176 (66.4)
11–15	25 (9.4)	2004–2014	11–20	50 (18.9)	Pre-2014	>10	89 (33.6)
16–20	25 (9.4)	2004–2014	11–20	50 (18.9)
21–25	12 (4.5)	pre-2004	>20	39 (14.7)
26–30	5 (1.9)
31+	22 (8.3)

Pre-2004 treatment era represents most experienced group with knowledge and first-hand experience with AIDS related wasting and older ART (old protease inhibitors [PIs] and older nucleoside reverse transcriptase inhibitors [NRTIs]).

Treatment era 2004–2014 represents HCPs with some experience and knowledge with AIDS related wasting than other group.

ART use was mostly with newer PI/ non-nucleoside reverse transcriptase inhibitors (NNRTIs) and pre-integrase strand transfer inhibitors (INSTIs); 2014 to present treatment era represents HCPs with minimal experience with wasting.

Disease awareness

Approximately half (49.9%) of all 345 responders agreed that HIVAW has a prevalence rate of 3%, although many acknowledged challenges in its detection, particularly due to weight gain from other factors. In addition, 39.4% indicated that HIVAW is more likely to occur in PWH who are not receiving ART (Fig. 1).

FIG. 1.

Awareness of HIVAW among all responders (N = 345). ART, Antiretroviral therapy; HIV, human immunodeficiency virus; HIVAW, HIV-associated wasting; PWH, people with HIV.

The majority (69.3%) of all responders agreed that HIVAW is associated with increased morbidity, mortality, and health care resource utilization (HCRU). Conversely, 22.3% acknowledged being unfamiliar with the morbidity, mortality, and HCRU associated with HIVAW. Among the 265 completers, 49.1% agreed that HIVAW has a prevalence rate of 3%; this view was shared by 51.1% of those practicing since 2014 (n = 176) and 44.0% of those practicing since 2004 (n = 50). In addition, 39.6% of completers believed that HIVAW is more likely to occur in PWH who are not receiving ART, with similar responses from those practicing since 2014 (40.3%) and since 2004 (38.0%). These data indicate a consistent understanding of HIVAW across treatment eras (p = .3460), demonstrating no significant differences in perspectives based on years of practice.

Diagnosis/screening and endurance

Overall, 52.8% of all 345 responders reported that they saw patients and treated them as needed, whereas 29.6% indicated they had not encountered patients with HIVAW in recent years. Further, 29.6% of all responders found it challenging to diagnose HIVAW because of a lack of clear definitions and guidelines.

In consideration of screening practices, 23.2% of the responders did not screen for HIVAW, whereas 39.4% of all responders screened based on weight loss and ART adherence, and 37.4% of all responders relied on body mass index (BMI) and physical endurance assessments (Fig. 2).

FIG. 2.

Experience with screening for HIVAW among all responders (N = 345). ART, Antiretroviral therapy; BMI, Body mass index; HIV, human immunodeficiency virus; HIVAW, HIV-associated wasting.

Only 16.8% of the 345 responders consistently followed up with patients about decreased physical endurance at every visit, and 6.4% of them never inquiring about this aspect of patient health.

With regard to the number of years in practice, 24.9% of 265 completers had not seen patients with HIVAW in recent years, with 26.1% of those practicing since 2014 (n = 176) and 22.5% of those practicing before 2014 (n = 89) reporting the same (Fig. 3).

FIG. 3.

Percentage of HCPs who agree with the following statements regarding diagnosing HIVAW by years of practice. HCPs, health care practitioners; HIV, human immunodeficiency virus; HIVAW, HIV-associated wasting.

More than half (55.8%) of the completers treated a few patients with HIVAW in an individualized manner, with similar rates for those practicing since 2014 (55.7%) and before 2014 (56.2%) (Fig. 3).

Notably, 35.8% of the completers practicing for 10 years or less found it challenging to diagnose HIVAW due to unclear definitions and guidelines compared to 22.5% of HCPs practicing for more than 10 years, demonstrating a significant difference based on years of treating patients with HIV (p = .0351) (Fig. 3).

With regard to screening practices for HIVAW, 37.7% of completers reported using BMI and symptoms of decreased physical endurance only for individuals with significant weight loss (over 10%) or a BMI of <20. Among these, 35.2% had 10 years or less of experience, while 42.7% had more than 10 years of experience.

Screening for HIVAW by using weight loss of 10% or more and whether patients were ART adherent was reported by 42.7% of the completers (20.4% considering adherence to ART and 22.3% considering non-adherence to ART).

No significant difference in response between those practicing for up to 10 versus 11–20 versus >21 years (p = .1392) was observed in terms of agreeing that HIVAW is associated with morbidity, mortality, and HCRU by years of treatment of PWH.

Treatment approaches and challenges

The majority (88.4% of 345) of all responders were aware of nutritional supplements and appetite stimulants as interventions for medical intervention to manage HIVAW. Further, 53.9% recognized physical exercise, 40.9% were aware of hGH, and 39.1% acknowledged anabolic steroids as treatment options.

Regarding FDA-approved medications for HIVAW, only 32.2% (n = 99) of all responders were aware of somatropin being such a medication. Among those, 58.6% (n = 58) were able to name somatropin alone or with at least one other medication, with 50.5% (n = 50) identifying somatropin alone. Nutritional supplements were preferred first in ranking treatment approaches for HIVAW, followed by appetite stimulants and then testosterone replacement (Fig. 4). Furthermore, 67% of all responders ranked nutritional supplements as their first choice, followed by 59% ranking appetite stimulants as their second choice.

FIG. 4.

Ranking of treatment approaches for HIV-associated wasting according to years of HCP experience. HCPs, healthcare practitioners; HIV, human immunodeficiency virus; HIVAW, HIV-associated wasting.

In terms of treatment challenges, 31.7% of the 265 completers identified a lack of clear treatment guidelines, whereas 21.5% noted a lack of prior experience with or knowledge about HIVAW as the two most predominant challenges.

In terms of practice year analysis, 42% of completers were aware of hGH (e.g., somatropin); however, higher awareness was reported in HCPs practicing >10 years versus ≤10 years (63% versus 31%, respectively, p < .001). Similarly, awareness of anabolic steroids was reported by 40% overall, with significant differences observed between the same two practice groups (p < .0001).

Overall, 17.0% of all completers report asking about decreased physical endurance at every visit, while 6.8% never ask about endurance. There was no significant difference in the response of those practicing for up to 10 versus 11–20 versus more than 20 years (p = .1074) in terms of endurance. Among completers, 70.9% expressed concern about frailty among older patients with HIV, with 73.9% of those practicing since 2014 sharing this view. Furthermore, 54.3% recognized weight loss as part of frailty syndrome, whereas only 26.4% routinely screened older patients for frailty, with a lower rate of 25.0% for those practicing since 2014.

Discussion

The results of this study provide important insights into the contemporary landscape of HIVAW management among HCPs and highlight the complex challenges they encounter in diagnosing and managing people with HIVAW.

Unlike the historical “HIV wasting syndrome” defined by severe viremia and opportunistic infections, modern HIV-associated weight loss is often multifactorial and may be driven by chronic inflammation, metabolic shifts, and social determinants such as food insecurity. As the population of PWH ages, this condition increasingly intersects geriatric syndromes like frailty and sarcopenia, significantly predicting higher mortality and health care costs.^9,15

The survey data indicated that approximately half of the respondents were actively treating PWH with wasting, whereas approximately one-third had not encountered patients with HIVAW in recent years. This variance raises critical questions about the visibility and recognition of HIVAW in clinical practice, suggesting potential underdiagnosis that could adversely affect patient outcomes. The lack of recent encounters with people with HIVAW among a substantial proportion of HCPs highlights the need for increased awareness and education about this condition, particularly given its implications for morbidity and mortality in the HIV population.

The demographic analysis of the current study revealed a predominantly younger cohort of providers, with 67.2% aged under 45 years primarily practicing in urban locations. This trend may facilitate the adoption of innovative therapeutic strategies and clinical guidelines, yet it also highlights the necessity for ongoing education to tackle the complex challenges associated with HIVAW. Given the disparities in access to nutrition services, endocrinology, rehabilitation, and exercise programs, these factors may further influence awareness and management approaches. In addition, urban-dominant sampling could account for the increased familiarity with nutritional supplementation compared to pharmacologic or multidisciplinary strategies.

The identified challenges—most notable being the absence of clear definitions and standardized guidelines—emphasizes the pressing need for the establishment of standardized diagnostic criteria and comprehensive training resources. The correlation between years of experience in treating PWH and the reported difficulties in diagnosing HIVAW indicates that providers may face more complex patient presentations as they gain experience. This evolving landscape requires an ongoing commitment to professional development to ensure that HCPs are adequately equipped to recognize and manage HIVAW with competence.

Regarding screening practices, approximately one-fourth of the respondents routinely screen for HIVAW, with notable variations based on years of practice. This inconsistency in screening practices could contribute to the underdiagnosis and inadequate management of patients experiencing weight loss or wasting. A significant variance in translating this understanding into clinical practice remains despite most respondents acknowledging the association between HIVAW and increased morbidity, mortality, and HCRU. Approximately one-third of the respondents found it exceedingly difficult to diagnose HIVAW due to unclear definitions, highlighting the critical need for clear guidelines and training resources to support HCPs in their clinical decision-making.

In the management of HIVAW, HCPs predominantly prioritize nutritional supplements and appetite stimulants as initial therapeutic options. This inclination is likely attributable to their relative ease of recommendation, availability, and higher likelihood of insurance coverage. However, awareness of the diverse array of treatment modalities varies significantly based on HCPs’ clinical experience with HIV. More experienced providers tend to possess greater insight regarding available pharmacological interventions, including hGH and anabolic steroids.

Despite a general understanding of nutritional strategies, there exists a concerning deficit in awareness regarding FDA-approved medications specifically indicated for HIVAW, with only 32.2% of respondents demonstrating familiarity with this option. This knowledge gap stresses the need for comprehensive educational initiatives aimed at elucidating the full spectrum of treatment modalities, as it could significantly impede optimal patient care.

Furthermore, it is vital for HCPs to differentiate between HIVAW or weight loss or cachexia as part of a frailty syndrome, as these conditions often exhibit considerable overlap and are frequently characterized by weight loss. Sarcopenic obesity often represents a biological substrate of frailty rather than a distinct competing diagnosis.¹⁶ Heightened awareness of frailty, particularly among more experienced providers, may enhance the screening process for wasting and facilitate timely initiation of treatment for frailty when indicated. The systematic integration of frailty and weight loss assessments into routine clinical practice is essential for the early identification of at-risk individuals, thereby enabling prompt interventions that can ameliorate the deleterious effects of both frailty and HIVAW.¹⁷ Given that over 70% of respondents expressed concerns regarding frailty in older patients with HIV, a comprehensive and holistic approach to management is imperative, including the implementation of routine frailty screening, which currently stands at a notably low rate of 26.4%. This approach ensures that aging patients receive care that is tailored to their unique clinical needs.¹⁷

To the best of our knowledge, this survey is the first to examine the knowledge and attitudinal factors that may impede clinicians from timely recognizing and treating wasting in patients with HIV. Respondents reported various challenges and opportunities encountered in managing patients with HIVAW. The survey results indicate that years of experience treating patients with HIV not only affects baseline knowledge of wasting but also familiarity with the range of products available for treatment.

This study had several strengths, including a large sample size of respondents, which provided a robust dataset for analysis, and the wide distribution through AAHIVM, a professional membership organization, thus ensuring that a geographically diverse group of HIV-care providers across the U.S. participated.

The survey focused on a specific and clinically relevant condition, HIVAW, contributing to an understanding of the current state of provider knowledge and treatment practices.

However, a few limitations are notable. The reliance on self-reported data may introduce bias, as respondents could overestimate their knowledge or practices. Furthermore, the cross-sectional design limits the ability to draw causal inferences regarding the associations between knowledge, attitudes, and practices.

In summary, although HCPs possess a foundational understanding of HIVAW, significant gaps remain in diagnosis, screening, and treatment practices. Addressing these gaps through targeted education, clear guidelines, and increased awareness will be essential for improving the quality of care for individuals with HIVAW.

Future research should focus on developing and implementing standardized protocols as well as evaluating the effectiveness of educational interventions aimed at improving HCP knowledge and practices related to HIVAW. These efforts will be essential to ensure that HCPs are adequately equipped to address the complexities of HIVAW and improve health outcomes for this vulnerable population.

Conclusion

This study reveals a substantial gap in the screening practices and management of HIVAW among HCPs, as approximately 25% do not screen for this critical condition. Experienced clinicians demonstrated greater confidence in diagnosing and treating HIVAW, particularly through the use of nutritional supplements. However, the persistent challenges of unclear treatment guidelines and limited awareness of available therapies underscore the need for enhanced education and standardized protocols to improve patient care for HIVAW.

Data Accessibility Statement

Any requests for data by qualified scientific and medical researchers for legitimate research purposes will be subject to EMD Serono’s Data-Sharing Policy. All requests should be submitted in writing to EMD Serono’s data-sharing portal (Link). When EMD Serono has a co-research, co-development, or co-marketing or co-promotion agreement, or when the product has been unlicensed, the responsibility for disclosure might be dependent on the agreement between the parties. Under these circumstances, EMD Serono will endeavor to gain agreement to share data in response to requests.

Authors’ Contributions

All authors meet the four criteria for authorship as identified by the International Committee of Medical Journal Editors (ICMJE). D.L.: Conceptualization, methodology, drafting and reviewing this article. S.B.: Conceptualization, methodology, data collection, drafting and reviewing article. B.H.: Conceptualization, methodology, statistical analysis, drafting and reviewing this article. E.M., M.H., and J.F.: Conceptualization, methodology, supervision, drafting and reviewing article.

Footnotes

Acknowledgment

The authors would like to thank Yukti Singh, M.Pharm (Merck Specialties Pvt. Ltd., Bangalore, India, an affiliate of Merck KGaA, Darmstadt, Germany) for providing medical writing and editorial support, which was funded by Merck KGaA, Darmstadt, Germany.

Author Disclosure Statement

No competing financial interests exist.

Funding Information

This study was financially supported by EMD Serono.

Supplemental Material

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