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  1. Article: Benefit-risk assessment of brensocatib for treatment of non-cystic fibrosis bronchiectasis.

    Chalmers, James D / Metersky, Mark L / Feliciano, Joseph / Fernandez, Carlos / Teper, Ariel / Maes, Andrea / Hassan, Mariam / Chatterjee, Anjan

    ERJ open research

    2023  Volume 9, Issue 3

    Abstract: Brensocatib is a novel anti-inflammatory therapy in development for bronchiectasis treatment. Phase 2 WILLOW trial data demonstrate a low number needed to treat and negative number needed to harm, suggesting a favourable benefit-risk profile. ...

    Abstract Brensocatib is a novel anti-inflammatory therapy in development for bronchiectasis treatment. Phase 2 WILLOW trial data demonstrate a low number needed to treat and negative number needed to harm, suggesting a favourable benefit-risk profile.
    Language English
    Publishing date 2023-05-02
    Publishing country England
    Document type Journal Article
    ZDB-ID 2827830-6
    ISSN 2312-0541
    ISSN 2312-0541
    DOI 10.1183/23120541.00695-2022
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Good Manufacturing Practice-compliant change of raw material in the manufacturing process of a clinically used advanced therapy medicinal product-a comparability study.

    Wixmerten, Anke / Miot, Sylvie / Bittorf, Patrick / Wolf, Francine / Feliciano, Sandra / Hackenberg, Stephan / Häusner, Sebastian / Krenger, Werner / Haug, Martin / Martin, Ivan / Pullig, Oliver / Barbero, Andrea

    Cytotherapy

    2023  Volume 25, Issue 5, Page(s) 548–558

    Abstract: The development of medicinal products often continues throughout the different phases of a clinical study and may require challenging changes in raw and starting materials at later stages. Comparability between the product properties pre- and post-change ...

    Abstract The development of medicinal products often continues throughout the different phases of a clinical study and may require challenging changes in raw and starting materials at later stages. Comparability between the product properties pre- and post-change thus needs to be ensured. Here, we describe and validate the regulatory compliant change of a raw material using the example of a nasal chondrocyte tissue-engineered cartilage (N-TEC) product, initially developed for treatment of confined knee cartilage lesions. Scaling up the size of N-TEC as required for the treatment of larger osteoarthritis defects required the substitution of autologous serum with a clinical-grade human platelet lysate (hPL) to achieve greater cell numbers necessary for the manufacturing of larger size grafts. A risk-based approach was performed to fulfill regulatory requirements and demonstrate comparability of the products manufactured with the standard process (autologous serum) already applied in clinical indications and the modified process (hPL). Critical attributes with regard to quality, purity, efficacy, safety and stability of the product as well as associated test methods and acceptance criteria were defined. Results showed that hPL added during the expansion phase of nasal chondrocytes enhances proliferation rate, population doublings and cell numbers at passage 2 without promoting the overgrowth of potentially contaminant perichondrial cells. N-TEC generated with the modified versus standard process contained similar content of DNA and cartilaginous matrix proteins with even greater expression levels of chondrogenic genes. The increased risk for tumorigenicity potentially associated with the use of hPL was assessed through karyotyping of chondrocytes at passage 4, revealing no chromosomal changes. Moreover, the shelf-life of N-TEC established for the standard process could be confirmed with the modified process. In conclusion, we demonstrated the introduction of hPL in the manufacturing process of a tissue engineered product, already used in a late-stage clinical trial. Based on this study, the national competent authorities in Switzerland and Germany accepted the modified process which is now applied for ongoing clinical tests of N-TEC. The described activities can thus be taken as a paradigm for successful and regulatory compliant demonstration of comparability in advanced therapy medicinal products manufacturing.
    MeSH term(s) Humans ; Chondrocytes ; Tissue Engineering ; Karyotyping ; Knee Joint
    Language English
    Publishing date 2023-03-07
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2039821-9
    ISSN 1477-2566 ; 1465-3249
    ISSN (online) 1477-2566
    ISSN 1465-3249
    DOI 10.1016/j.jcyt.2023.01.003
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Political participation and social exclusion in later life

    Rodrigo Serrat / Jeni Warburton / Andrea Petriwskyj / Feliciano Villar

    International Journal of Ageing and Later Life, Vol 12, Iss

    What politically active seniors can teach us about barriers to inclusion and retention

    2018  Volume 2

    Abstract: Addressing older people’s social exclusion is a major challenge for contemporary societies. However, policies designed to address it have tended to focus on poverty and unemployment. This paper explores the relationship between social exclusion and ... ...

    Abstract Addressing older people’s social exclusion is a major challenge for contemporary societies. However, policies designed to address it have tended to focus on poverty and unemployment. This paper explores the relationship between social exclusion and political participation from the perspective of those already holding responsible roles within seniors’ organisations. We aim to highlight the impact of later-life social exclusion in relation to politically active older individuals from two diverse socio-political contexts, Australia and Spain. Participants perceived a range of potential barriers for the inclusion of new members and their own continued involvement. These related to practical and resource ssues, beliefs and attitudes towards participation, and organisational and contextual issues. Members’ views of retention of existing members as well as the recruitment of new members highlight the complexity associated with building the diversity and representativeness that organisations need if they are to represent seniors’ views in the policy process.
    Keywords seniors’ interest organisations ; political participation ; barriers ; retention ; inclusion ; Social sciences (General) ; H1-99
    Subject code 300
    Language English
    Publishing date 2018-10-01T00:00:00Z
    Publisher Linköping University Electronic Press
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  4. Article ; Online: Leveraging a Digitized Mental Wellness (DIGImw) Program to Provide Mental Health Care for Internally Displaced People.

    Mootz, Jennifer J / Chantre, Catherine / Sikkema, Kathleen / Greene, M Claire / Lovero, Kathryn L / Gouveia, Lidia / Santos, Palmira / Suleman, Antonio / Comé, Andrea Simone / Feliciano, Paulino / Uribe-Restrepo, José Miguel / Sweetland, Annika C / Shelton, Rachel C / Kane, Jeremy / Mello, Milena / Fumo, Wilza / Cadena-Camargo, Yazmin / Weissman, Myrna / Wainberg, Milton L

    Psychiatric services (Washington, D.C.)

    2023  Volume 75, Issue 1, Page(s) 98–101

    Abstract: A local insurgency has displaced many people in the northern Mozambican province of Cabo Delgado. The authors' global team (comprising members from Brazil, Mozambique, South Africa, and the United States) has been scaling up mental health services across ...

    Abstract A local insurgency has displaced many people in the northern Mozambican province of Cabo Delgado. The authors' global team (comprising members from Brazil, Mozambique, South Africa, and the United States) has been scaling up mental health services across the neighboring province of Nampula, Mozambique, now host to >200,000 displaced people. The authors describe how mental health services can be expanded by leveraging digital technology and task-shifting (i.e., having nonspecialists deliver mental health care) to address the mental health needs of displaced people. These methods can serve as a model for other researchers and clinicians aiming to address mental health needs arising from humanitarian disasters in low-resource settings.
    MeSH term(s) Humans ; Mental Health ; Mental Health Services ; Disasters ; Mozambique ; South Africa
    Language English
    Publishing date 2023-07-18
    Publishing country United States
    Document type Journal Article
    ZDB-ID 1220173-x
    ISSN 1557-9700 ; 1075-2730
    ISSN (online) 1557-9700
    ISSN 1075-2730
    DOI 10.1176/appi.ps.202100552
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Pre- and post-COVID-19 evaluation of antimicrobial susceptibility for healthcare-associated infections in the intensive care unit of a tertiary hospital.

    Gaspar, Gilberto Gambero / Ferreira, Lécio Rodrigues / Feliciano, Cinara Silva / Campos Júnior, Cláudio Penido / Molina, Fabiana Murad Rossin / Vendruscolo, Andrea Cristina Soares / Bradan, Giovana Marcão Araújo / Lopes, Nátali Artal Padovani / Martinez, Roberto / Bollela, Valdes Roberto

    Revista da Sociedade Brasileira de Medicina Tropical

    2021  Volume 54, Page(s) e00902021

    Abstract: Introduction: Antimicrobial resistance has worsened since the onset of COVID-19.: Methods: This study involved patients admitted to the adult intensive care unit (ICU) of a tertiary hospital. Pre- and post-COVID-19 data were analyzed. The healthcare- ... ...

    Abstract Introduction: Antimicrobial resistance has worsened since the onset of COVID-19.
    Methods: This study involved patients admitted to the adult intensive care unit (ICU) of a tertiary hospital. Pre- and post-COVID-19 data were analyzed. The healthcare-related infections (HCRIs) reported between January 2018 and January 2020 and during the pandemic between February and July 2020 were compared.
    Results: Antimicrobial resistance increased during the pandemic, especially for Klebsiella pneumoniae isolates, with a rate increase from 5% to 50% for Polymyxin B.
    Conclusions: The susceptibilities of the main pathogens associated with HCRIs in the ICU changed and should be considered in managing severe COVID-19.
    MeSH term(s) Adult ; Anti-Bacterial Agents/pharmacology ; Anti-Bacterial Agents/therapeutic use ; COVID-19 ; Cross Infection/drug therapy ; Delivery of Health Care ; Drug Resistance, Bacterial ; Humans ; Intensive Care Units ; Microbial Sensitivity Tests ; SARS-CoV-2 ; Tertiary Care Centers
    Chemical Substances Anti-Bacterial Agents
    Language English
    Publishing date 2021-07-23
    Publishing country Brazil
    Document type Journal Article
    ZDB-ID 1038126-0
    ISSN 1678-9849 ; 0037-8682
    ISSN (online) 1678-9849
    ISSN 0037-8682
    DOI 10.1590/0037-8682-0090-2021
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: Long-term Trajectories of Physical Function Decline in Women With and Without Cancer.

    Cespedes Feliciano, Elizabeth M / Vasan, Sowmya / Luo, Juhua / Binder, Alexandra M / Chlebowski, Rowan T / Quesenberry, Charles / Banack, Hailey R / Caan, Bette J / Paskett, Electra D / Williams, Grant R / Barac, Ana / LaCroix, Andrea Z / Peters, Ulrike / Reding, Kerryn W / Pan, Kathy / Shadyab, Aladdin H / Qi, Lihong / Anderson, Garnet L

    JAMA oncology

    2023  Volume 9, Issue 3, Page(s) 395–403

    Abstract: Importance: Patients with cancer experience acute declines in physical function, hypothesized to reflect accelerated aging driven by cancer-related symptoms and effects of cancer therapies. No study has examined long-term trajectories of physical ... ...

    Abstract Importance: Patients with cancer experience acute declines in physical function, hypothesized to reflect accelerated aging driven by cancer-related symptoms and effects of cancer therapies. No study has examined long-term trajectories of physical function by cancer site, stage, or treatment compared with cancer-free controls.
    Objective: Examine trajectories of physical function a decade before and after cancer diagnosis among older survivors and cancer-free controls.
    Design, setting, and participants: This prospective cohort study enrolled patients from 1993 to 1998 and followed up until December 2020. The Women's Health Initiative, a diverse cohort of postmenopausal women, included 9203 incident cancers (5989 breast, 1352 colorectal, 960 endometrial, and 902 lung) matched to up to 5 controls (n = 45 358) on age/year of enrollment and study arm.
    Exposures: Cancer diagnosis (site, stage, and treatment) via Medicare and medical records.
    Main outcomes and measures: Trajectories of self-reported physical function (RAND Short Form 36 [RAND-36] scale; range: 0-100, higher scores indicate superior physical function) estimated from linear mixed effects models with slope changes at diagnosis and 1-year after diagnosis.
    Results: This study included 9203 women with cancer and 45 358 matched controls. For the women with cancer, the mean (SD) age at diagnosis was 73.0 (7.6) years. Prediagnosis, physical function declines of survivors with local cancers were similar to controls; after diagnosis, survivors experienced accelerated declines relative to controls, whose scores declined 1 to 2 points per year. Short-term declines in the year following diagnosis were most severe in women with regional disease (eg, -5.3 [95% CI, -6.4 to -4.3] points per year in regional vs -2.8 [95% CI, -3.4 to -2.3] for local breast cancer) or who received systemic therapy (eg, for local endometrial cancer, -7.9 [95% CI, -12.2 to -3.6] points per year with any chemotherapy; -3.1 [95% CI, -6.0 to -0.3] with radiation therapy alone; and -2.6 [95% CI, -4.2 to -1.0] with neither, respectively). While rates of physical function decline slowed in the later postdiagnosis period (eg, women with regional colorectal cancer declined -4.3 [95% CI, -5.9 to -2.6] points per year in the year following diagnosis vs -1.4 [95% CI, -1.7 to -1.0] points per year in the decade thereafter), survivors had estimated physical function significantly below that of age-matched controls 5 years after diagnosis.
    Conclusions and relevance: In this prospective cohort study, survivors of cancer experienced accelerated declines in physical function after diagnosis, and physical function remained below that of age-matched controls even years later. Patients with cancer may benefit from supportive interventions to preserve physical functioning.
    MeSH term(s) Humans ; Female ; Aged ; United States ; Prospective Studies ; Medicare ; Breast Neoplasms/epidemiology ; Breast Neoplasms/therapy ; Breast Neoplasms/diagnosis ; Women's Health
    Language English
    Publishing date 2023-01-19
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural
    ISSN 2374-2445
    ISSN (online) 2374-2445
    DOI 10.1001/jamaoncol.2022.6881
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: Stem cell microRNAs in senescence and immortalization: novel players in cancer therapy.

    Leal, Jose A / Feliciano, Andrea / Lleonart, Matilde E

    Medicinal research reviews

    2013  Volume 33, Issue 1, Page(s) 112–138

    Abstract: The molecular etiology of malignancy remains one of the most challenging disease processes under scientific investigation; therefore, improved approaches for their treatment are urgently needed. MicroRNAs are highly conserved nonprotein-coding RNAs that ... ...

    Abstract The molecular etiology of malignancy remains one of the most challenging disease processes under scientific investigation; therefore, improved approaches for their treatment are urgently needed. MicroRNAs are highly conserved nonprotein-coding RNAs that regulate gene expression. They are involved in important homeostatic processes, such as cellular proliferation, cell death and development, and affect many diseases, including cancer. High-throughput screenings based on microRNAs related to senescence/immortalization are potential tools for identifying novel proliferative microRNAs that might be involved in carcinogenesis. Recently, a subgroup of highly proliferative microRNAs, which belong to a cluster expressed exclusively in embryonic stem cells and their malignant derivatives (embryonic carcinoma cells), was revealed to play a role in senescence bypass, thereby providing immortalization to human cells. This finding supports the cancer stem cell theory and the relevance of microRNAs in human tumors. This article recapitulates the role of microRNAs that are associated with stem cell properties and their possible link in common pathways related to immortalization and cancer. Ultimately, cancer therapy that is based on the induction of a senescence response is proposed to be highly associated with the loss of stemness properties. Thus, it would be possible to "kill two birds with one stone": along with the inhibition of stemness properties in cancer stem cells, the senescence response could be induced to destroy the cancer stem cell population within a tumor.
    MeSH term(s) Animals ; Cell Proliferation ; Cell Transformation, Neoplastic/genetics ; Cellular Senescence ; Embryonic Stem Cells/cytology ; Embryonic Stem Cells/metabolism ; Embryonic Stem Cells/pathology ; Humans ; MicroRNAs/genetics ; MicroRNAs/metabolism ; Neoplasms/genetics ; Neoplasms/pathology ; Neoplasms/therapy ; Neoplastic Stem Cells/metabolism ; Neoplastic Stem Cells/pathology ; Stem Cells/cytology ; Stem Cells/metabolism
    Chemical Substances MicroRNAs
    Language English
    Publishing date 2013-01
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 603210-2
    ISSN 1098-1128 ; 0198-6325
    ISSN (online) 1098-1128
    ISSN 0198-6325
    DOI 10.1002/med.20246
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article ; Online: Comparison of Human Articular Cartilage Tissue and Chondrocytes Isolated from Peripheral versus Central Regions of Traumatic Lesions.

    Acevedo, Lina / Iselin, Lukas / Berkelaar, Majoska H M / Salzmann, Gian M / Wolf, Francine / Feliciano, Sandra / Vogel, Nicole / Pagenstert, Geert / Martin, Ivan / Pelttari, Karoliina / Barbero, Andrea / Arnold, Markus P

    Cartilage

    2020  Volume 13, Issue 2_suppl, Page(s) 68S–81S

    Abstract: Objective: Cellular and molecular events occurring in cartilage regions close to injury are poorly investigated, but can possibly compromise the outcome of cell-based cartilage repair. In this study, key functional properties were assessed for cartilage ...

    Abstract Objective: Cellular and molecular events occurring in cartilage regions close to injury are poorly investigated, but can possibly compromise the outcome of cell-based cartilage repair. In this study, key functional properties were assessed for cartilage biopsies collected from the central part of traumatic joint lesions (
    Design: Cartilage samples were collected from knee joints of 42 patients with traumatic knee injuries and analyzed for cell phenotype (by reverse transcriptas-polymerase chain reaction), histological quality, cellularity, cell viability, proliferation capacity, and post-expansion chondrogenic capacity of chondrocytes (in pellet culture). Synovium was also harvested and analyzed for the expression of inflammatory cytokines.
    Results: Cartilage quality and post-expansion chondrogenic capacity were higher in
    Conclusions: Chondrocytes at the periphery of traumatic lesions better maintain properties of healthy cartilage compared to those isolated from the center, even when derived from bad-quality tissues harvested from highly inflamed joints. Future studies are necessary to investigate the change of functional properties of
    MeSH term(s) Aggrecans/metabolism ; Cartilage, Articular ; Cell Differentiation/genetics ; Chondrocytes/metabolism ; Chondrogenesis ; Humans
    Chemical Substances Aggrecans
    Language English
    Publishing date 2020-09-22
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2515870-3
    ISSN 1947-6043 ; 1947-6035
    ISSN (online) 1947-6043
    ISSN 1947-6035
    DOI 10.1177/1947603520958154
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article: Prostate cancer extracellular vesicles mediate intercellular communication with bone marrow cells and promote metastasis in a cholesterol-dependent manner.

    Henrich, Stephen E / McMahon, Kaylin M / Plebanek, Michael P / Calvert, Andrea E / Feliciano, Timothy J / Parrish, Samuel / Tavora, Fabio / Mega, Anthony / De Souza, Andre / Carneiro, Benedito A / Thaxton, C Shad

    Journal of extracellular vesicles

    2020  Volume 10, Issue 2, Page(s) e12042

    Abstract: Primary tumours can establish long-range communication with distant organs to transform them into fertile soil for circulating tumour cells to implant and proliferate, a process called pre-metastatic niche (PMN) formation. Tumour-derived extracellular ... ...

    Abstract Primary tumours can establish long-range communication with distant organs to transform them into fertile soil for circulating tumour cells to implant and proliferate, a process called pre-metastatic niche (PMN) formation. Tumour-derived extracellular vesicles (EV) are potent mediators of PMN formation due to their diverse complement of pro-malignant molecular cargo and their propensity to target specific cell types (Costa-Silva et al., 2015; Hoshino et al., 2015; Peinado et al., 2012; Peinado et al., 2017). While significant progress has been made to understand the mechanisms by which pro-metastatic EVs create tumour-favouring microenvironments at pre-metastatic organ sites, comparatively little attention has been paid to the factors intrinsic to recipient cells that may modify the extent to which pro-metastatic EV signalling is received and transduced. Here, we investigated the role of recipient cell cholesterol homeostasis in prostate cancer (PCa) EV-mediated signalling and metastasis. Using a bone metastatic model of enzalutamide-resistant PCa, we first characterized an axis of EV-mediated communication between PCa cells and bone marrow that is marked by in vitro and in vivo PCa EV uptake by bone marrow myeloid cells, activation of NF-κB signalling, enhanced osteoclast differentiation, and reduced myeloid thrombospondin-1 expression. We then employed a targeted, biomimetic approach to reduce myeloid cell cholesterol in vitro and in vivo prior to conditioning with PCa EVs. Reducing myeloid cell cholesterol prevented the uptake of PCa EVs by recipient myeloid cells, abolished NF-κB activity and osteoclast differentiation, stabilized thrombospondin-1 expression, and reduced metastatic burden by 77%. These results demonstrate that cholesterol homeostasis in bone marrow myeloid cells regulates pro-metastatic EV signalling and metastasis by acting as a gatekeeper for EV signal transduction.
    MeSH term(s) Animals ; Apoptosis ; Biomarkers, Tumor/genetics ; Biomarkers, Tumor/metabolism ; Bone Marrow Cells/metabolism ; Bone Marrow Cells/pathology ; Bone Neoplasms/genetics ; Bone Neoplasms/metabolism ; Bone Neoplasms/secondary ; Cell Communication ; Cell Proliferation ; Cholesterol/metabolism ; Extracellular Vesicles/genetics ; Extracellular Vesicles/metabolism ; Extracellular Vesicles/pathology ; Gene Expression Profiling ; Humans ; Male ; Mice ; Mice, Inbred C57BL ; Mice, SCID ; Prostatic Neoplasms/genetics ; Prostatic Neoplasms/metabolism ; Prostatic Neoplasms/pathology ; Signal Transduction ; Tumor Cells, Cultured ; Tumor Microenvironment ; Xenograft Model Antitumor Assays
    Chemical Substances Biomarkers, Tumor ; Cholesterol (97C5T2UQ7J)
    Language English
    Publishing date 2020-12-31
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 2683797-3
    ISSN 2001-3078
    ISSN 2001-3078
    DOI 10.1002/jev2.12042
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article ; Online: Efficacy, safety, tolerability, and pharmacokinetics of long-acting injectable cabotegravir for HIV pre-exposure prophylaxis in transgender women: a secondary analysis of the HPTN 083 trial.

    Marzinke, Mark A / Hanscom, Brett / Wang, Zhe / Safren, Steven A / Psaros, Christina / Donnell, Deborah / Richardson, Paul A / Sullivan, Philip / Eshleman, Susan H / Jennings, Andrea / Feliciano, Kailazarid Gomez / Jalil, Emilia / Coutinho, Carolina / Cardozo, Nadir / Maia, Bernardo / Khan, Taimur / Singh, Yashna / Middelkoop, Keren / Franks, Julie /
    Valencia, Javier / Sanchez, Naiymah / Lucas, Jonathan / Rooney, James F / Rinehart, Alex R / Ford, Susan / Adeyeye, Adeola / Cohen, Myron S / McCauley, Marybeth / Landovitz, Raphael J / Grinsztejn, Beatriz

    The lancet. HIV

    2023  Volume 10, Issue 11, Page(s) e703–e712

    Abstract: Background: The HIV Prevention Trials Network (HPTN) 083 trial showed that long-acting injectable cabotegravir was more effective than tenofovir disoproxil fumarate plus emtricitabine in preventing HIV in cisgender men and transgender women who have sex ...

    Abstract Background: The HIV Prevention Trials Network (HPTN) 083 trial showed that long-acting injectable cabotegravir was more effective than tenofovir disoproxil fumarate plus emtricitabine in preventing HIV in cisgender men and transgender women who have sex with men. We aimed to characterise the cohort of transgender women included in HPTN 083.
    Methods: HPTN 083 is an ongoing, phase 2b/3, randomised, multicentre, double-blind, double-dummy clinical trial done at 43 sites in seven countries (Argentina, Brazil, Peru, the USA, South Africa, Thailand, and Viet Nam). HIV-negative participants were randomly assigned (1:1) to receive injectable cabotegravir or tenofovir disoproxil fumarate plus emtricitabine. The study design and primary outcomes of the blinded phase of HPTN 083 have already been reported. An enrolment minimum of 10% transgender women was set for the trial. Here we characterise the cohort of transgender women enrolled from Dec 6, 2016, to May 14, 2020, when the study was unblinded. We report sociodemographic characteristics, use of gender affirming hormone therapy, and behavioural assessments of the transgender women participants. Laboratory testing and safety evaluations are also reported. The trial is registered at ClinicalTrials.gov, NCT02720094.
    Findings: HPTN 083 enrolled 570 transgender women (304 tenofovir disoproxil fumarate plus emtricitabine; 266 injectable cabotegravir). Transgender women were primarily from Asia (225 [39%]) and Latin America (205 [36%]); 330 (58%) reported using gender affirming hormone therapy. Intimate partner violence was common (270 [47%] reported emotional abuse and 172 [30%] reported physical abuse) and 323 (57%) reported a history of childhood sexual abuse. 159 (28%) transgender women disagreed that they were at risk for HIV, and 142 (25%) screened positive for depressive symptoms. During study follow-up, incidence of syphilis was 16·25% (95% CI 13·28-19·69), rectal gonorrhoea was 11·66% (9·14-14·66), and chlamydia was 20·61% (17·20-24·49). Frequency of adverse events was similar between the treatment groups. Nine seroconversions occurred among transgender women during the blinded phase of the study (seven in the tenofovir disoproxil fumarate plus emtricitabine group and two in the injectable cabotegravir group); overall incidence was 1·19 per 100 person-years (95% CI 0·54-2·25): 1·80 per 100 person-years (0·73-3·72) in the tenofovir disoproxil fumarate plus emtricitabine group and 0·54 per 100 person-years (0·07-1·95) in the injectable cabotegravir group (hazard ratio 0·34 [95% CI 0·08-1·56]). Cabotegravir concentrations did not differ by gender affirming hormone therapy use.
    Interpretation: HIV prevention strategies for transgender women cannot be addressed separately from social and structural vulnerabilities. Transgender women were well represented in HPTN 083 and should continue to be prioritised in HIV prevention studies. Our results suggest that injectable cabotegravir is a safe and effective pre-exposure prophylaxis option for transgender women.
    Funding: National Institute of Allergy and Infectious Diseases and ViiV Healthcare.
    MeSH term(s) Female ; Humans ; Male ; Acquired Immunodeficiency Syndrome/drug therapy ; Anti-HIV Agents/adverse effects ; Emtricitabine/therapeutic use ; HIV Infections/drug therapy ; HIV-1 ; Hormones/therapeutic use ; Pre-Exposure Prophylaxis/methods ; Tenofovir/therapeutic use ; Thailand ; Transgender Persons
    Chemical Substances Anti-HIV Agents ; cabotegravir (HMH0132Z1Q) ; Emtricitabine (G70B4ETF4S) ; Hormones ; Tenofovir (99YXE507IL)
    Language English
    Publishing date 2023-09-29
    Publishing country Netherlands
    Document type Clinical Trial, Phase II ; Clinical Trial, Phase III ; Journal Article ; Multicenter Study ; Randomized Controlled Trial ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ISSN 2352-3018
    ISSN (online) 2352-3018
    DOI 10.1016/S2352-3018(23)00200-X
    Database MEDical Literature Analysis and Retrieval System OnLINE

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