D-peptide hydrogels as a long-acting multipurpose drug delivery platform for combined contraception and HIV prevention

Journal of Controlled Release, Journal Year: 2025, Volume and Issue: 379, P. 30 - 44

Published: Jan. 8, 2025

New multipurpose prevention technology products for use by women, focused on reducing HIV infection and preventing unwanted pregnancies, are a global health priority. Discreet long-acting formulations will empower women with greater choice around their sexual health. This paper outlines the development of that enables multiple drugs to be incorporated within one injectable platform. fixed-dose combination product is formed from phosphorylated D-peptide (naphthalene-2-ly)-acetyl-diphenylalanine-lysine-tyrosine-glycine-OH (Napffky(p)G-OH) highly hydrophobic MIV-150 (HIV antiretroviral) etonogestrel (contraceptive) solubilized together aqueous solvents. Upon subcutaneous injection, this D-peptide-drug self-assembles in response phosphatase enzymes present skin space form an situ forming drug-releasing hydrogel depot. Oscillatory rheology confirmed formation hydrogels, which began ~10 s exposure 3.98 U/mL continued ~198 mins Napffk(MIV-150)y(p)G-OH + Napffk(ENG)y(p)G-OH (8:2 ratio). Biostability against proteases, important consideration injectables, was demonstrated at least 28 days vitro. Covalent attachment each drug via ester linkage enabled sustained release unmodified hydrolysis linker. significantly reduced initial burst. Low toxicity also vitro cell culture (MTS, LHS, Live/Dead®) vivo studies (H&E staining). The fixed dose able deliver clinically relevant concentrations Sprague-Dawley rats 49 days, providing proof-of-concept hydrogel-forming D-peptides as platform delivery drugs.

Language: Английский

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In Situ Forming, Enzyme-Responsive Peptoid-Peptide Hydrogels: An Advanced Long-Acting Injectable Drug Delivery System

Journal of the American Chemical Society, Journal Year: 2024, Volume and Issue: 146(31), P. 21401 - 21416

Published: June 26, 2024

Long-acting drug delivery systems are promising platforms to improve patient adherence medication by delivering drugs over sustained periods and removing the need for patients comply with oral regimens. This research paper provides a proof-of-concept development of new optimized in situ forming injectable depot based on tetrabenzylamine-tetraglycine-d-lysine-O-phospho-d-tyrosine peptoid-D-peptide formulation ((NPhe)4GGGGk(AZT)y(p)-OH). The chemical versatility peptoid-peptide motif allows low-molecular-weight be precisely covalently conjugated. After subcutaneous injection, hydrogel forms from solubilized peptoid-peptide-drug response phosphatase enzymes present within skin space. system is able deliver clinically relevant concentrations model drug, antiretroviral zidovudine (AZT), 35 days Sprague–Dawley rats. Oscillatory rheology demonstrated that formation began ∼30 s, an important characteristic reducing initial bursts. Gel continued up ∼90 min. Small-angle neutron scattering data reveal narrow-radius fibers (∼0.78–1.8 nm) closely fit via flexible cylinder elliptical model. inclusion non-native peptoid monomers D-variant amino acids confers protease resistance, enabling enhanced biostability vitro. Drug release proceeds hydrolysis ester linkage under physiological conditions, releasing unmodified form further burst. Subcutaneous administration (NPhe)4GGGGk(AZT)y(p)-OH rats resulted blood plasma 90% maximal inhibitory concentration (IC90) range (30–130 ng mL–1) days.

Language: Английский

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Knowledge and Awareness of Pre‐Exposure Prophylaxis Among Men in Sub‐Saharan Africa: A Scoping Review Protocol

Health Science Reports, Journal Year: 2025, Volume and Issue: 8(1)

Published: Jan. 1, 2025

ABSTRACT Introduction About 39.9 million people were living with HIV as of 2023, and is more prevalent in sub‐Saharan Africa. Pre‐exposure prophylaxis (PrEP) highly effective prevention. Despite the efficacy PrEP, many persons, including men, do not have adequate knowledge awareness reviews on among men are scarce. This review aims to assess synthesize PrEP persons assigned males at birth Methods Analysis The proposed scoping will be conducted accordance PRISMA Extension for Scoping Reviews (PRISMA‐ScR): Checklist Explanation. following information sources searched retrieve relevant studies this review: CINAHL, MEDLINE (Ovid), PubMed, SCOPUS, Web Science. Google Scholar, Union Catalogue Theses Dissertations (UCTD) SA ePublications via SABINET Online, WorldCat OCLC, ResearchGate, American Doctoral EBSCOhost. All study designs, except existing reviews, included. screenings (abstract screening full‐text screening) data extraction independently by two reviewers. Quantitative findings presented frequency percentages, while qualitative thematic analysis used analyze findings. Conclusion map out results give insights into what Africa know about which can inform future interventions.

Language: Английский

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Control of HIV across the WHO European region: progress and remaining challenges

The Lancet Regional Health - Europe, Journal Year: 2025, Volume and Issue: 52, P. 101243 - 101243

Published: Feb. 20, 2025

Language: Английский

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Evaluation of Xpert point-of-care assays for detection of HIV infection in persons using long-acting cabotegravir for pre-exposure prophylaxis

Microbiology Spectrum, Journal Year: 2024, Volume and Issue: 12(8)

Published: July 9, 2024

ABSTRACT Detection of HIV infection may be challenging in persons using long-acting cabotegravir (CAB-LA) pre-exposure prophylaxis (PrEP) due to viral suppression and reduced/delayed antibody production. We evaluated two point-of-care tests for detecting who received CAB-LA the HPTN 083 trial. Samples were obtained from 12 participants had delayed detection rapid an antigen/antibody test (52 plasma samples; 18 dried blood spot [DBS] samples). Plasma samples tested with Xpert HIV-1 Viral Load XC (Xpert VL-XC); DBS total nucleic acid Qual Qual-XC). Results these assays compared results three reference, laboratory-based, RNA (Aptima Qualitative assay [Aptima Qual]; Aptima Quant DX Assay Quant]; cobas HIV-1/HIV-2 Test [cobas]). was detected all four loads (VLs) ≥ 200 copies/mL; number VLs < copies/mL was: VL-XC: 19/26 (73.1%); Qual: 17/26 (65.4%); Quant: cobas: 12/21 (57.1%). The Qual-XC positive 1/10 copies/mL. performance VL-XC comparable reference cases. less sensitive than plasma-based setting PrEP. IMPORTANCE can detect infections earlier or Ag/Ab Earlier diagnosis could allow treatment initiation reduced risk INSTI resistance. POC help before administration more accessible laboratory-based some settings. In this study, most individuals PrEP test. similar cohort. detects both DNA, a higher load cutoff detection. This negative lower did not offer advantage screening

Language: Английский

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Transitions in treatment: A systematic review and meta‐aggregation of preferences and barriers in switching from oral to long‐acting injectable antiretroviral therapy among people living with HIV and stakeholders

HIV Medicine, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 2, 2025

Abstract Introduction Antiretroviral treatment (ART) has significantly enhanced health outcomes for people living with HIV (PLWH). With the evolution of options, there is an increasing interest in development long‐acting injectable formulations antiretroviral drugs. These present a promising alternative to oral ART. Methods The methodology and reporting this systematic review followed guidance Joanna Briggs Institute Reviewer's Manual Enhancing Transparency Reporting Synthesis Qualitative Research (ENTREQ). comprehensive searches involved multiple databases, including PubMed, MEDLINE (Ovid), Embase CINHAL (EBSCO), ProQuest Dissertations Theses, Web Science, Wanfang (Chinese), CNKI Google Scholar Baidu (Chinese). Results In all, 142 studies were identified 20 eligible included meta‐aggregation. A total 141 findings, categories nine synthesized findings extracted from studies. focused on following topics: benefits, flexibility practicality (LAI) treatment; scepticism about use LAI management challenges; logistical potential protecting marginalized populations; concerns side effects; financial issue; suggestions improvement. PLWH's geographical distribution, backgrounds, demographics clinical characteristics limited. Conclusion We recommend considering needs experiences PLWH transition ART treatment. For populations, it crucial maintain regular communication healthcare providers institutions. Additionally, at community level, engaging diverse stakeholders valuable insights vital, as enhancing education programmes intensifying efforts combat discrimination. measures will play key role addressing PLWH, public awareness promoting better understanding

Language: Английский

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Preferences for and acceptability of long-acting HIV prevention products among pregnant and lactating women accessing health services in Kenya: a mixed method cross-sectional analysis

BMC Infectious Diseases, Journal Year: 2025, Volume and Issue: 25(1)

Published: Jan. 7, 2025

Abstract Background Increased risk of HIV acquisition during pregnancy and lactation among women is evident, necessitating their inclusion in the evaluation new prevention interventions. Pregnant postpartum specifically face challenges with oral PrEP associated stigma, burden using other tablets. Long-acting products may address related to PrEP, however, there limited data on product-specific preferences acceptability pregnant lactating women. Methods We conducted a mixed-method study assess long-acting modalities either under development or already established quantitative surveys ( n = 434) in-depth interviews 80) central western Kenya. used descriptive statistics categorical variables summarize frequencies proportions. Inductive deductive content analytic approaches were for interviews. Results The median age respondents was 25 years (IQR 19.3–31.0). Majority married (263/434, 61%), had completed high school (222/434, 51%), no condoms use prior 3 months (348/434, 80%). most preferred formulations injectable (251/434, 57%) implantable (175/434, 40%) options. Participants who 8.56 times higher odds considering ease as reason. (aOR 8.56, 95% CI [3.81–20.48]) 3.71 choosing perceived discreteness 3.71, (1.57–9.97)) preference reasons. Implant 2.31 it due effectiveness preventing reason 2.31, (1.21—4.66)) 2.53-fold 2.53, (1.46—4.59)). From interviews, reported prospective convenience LA products, effectiveness, reduced cost, improved privacy, stigma. Women concerns regarding safety efficacy lactation. Conclusion Acceptability underscores importance unique needs breastfeeding future interventions . Aligning would enhance uptake adherence outcomes products.

Language: Английский

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Cabotegravir (Apretude)

Canadian Journal of Health Technologies, Journal Year: 2025, Volume and Issue: 5(1)

Published: Jan. 16, 2025

Reimbursement reviews are comprehensive assessments of the clinical effectiveness and cost-effectiveness, as well patient clinician perspectives, a drug or class. The inform nonbinding recommendations that help guide reimbursement decisions Canada’s federal, provincial, territorial governments, with exception Quebec. This review assesses cabotegravir (Apretude), 30 mg oral tablets 200 mg/mL (600 mg/3 mL), extended-release injectable suspension. Indication: For at-risk adults adolescents aged 12 years older weighing at least 35 kg for pre-exposure prophylaxis to reduce risk sexually acquired HIV-1 infection.

Language: Английский

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Willingness to Use Long-Acting Injectable Pre-Exposure Prophylaxis among Adolescent Girls and Young Women in Kampala, Uganda

AIDS and Behavior, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 30, 2025

Pre-exposure prophylaxis (PrEP) has proven to be a powerful tool in preventing HIV infection. There is limited information about the factors associated with willingness use different PrEP modalities among adolescent girls and young women (AGYW) Africa. We assessed long-acting injectable (LAI-PrEP) 14-24-year-old AGYW at high risk of Uganda, determined using multivariable complementary log-log regression. Of 285 participants, 69.8% participants showed LAI-PrEP despite only 3.9% having knowledge it before enrolment. Report recent transactional sex was (92.6%). Participants that were divorced/separated (aOR = 1.74, 95% CI 1.03–2.92) those multiple sexual partners 2.11, 1.46–3.06) compared one partner more likely willing while screened as heavy episodic drinkers (consuming 6 or drinks on an occasion per AUDIT tool) less 0.61, 0.42–0.87). LAI shown efficacy clinical trials; product approved for by Government Uganda (MoH) should expedited engaged paid partnerships. As becomes available, we recommend education counseling increase awareness alternative prevention method.

Language: Английский

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Framing HIV Pre-exposure Prophylaxis Use as a Public or Private Matter

AIDS Education and Prevention, Journal Year: 2025, Volume and Issue: 37(1), P. 74 - 88

Published: Feb. 1, 2025

PrEP campaigns often promote a “private” frame emphasizing personal HIV risk management. We explore how “public” community-managed sexual health is relevant among men who have sex with (MSM) and can advance prevention. sampled MSM from the United States (N = 311 in 2015) Netherlands 222 2020) soon after each country's official introduction to study early adoption of frames. Using regressions machine learning, we quantified support for different frames, person-level correlates, relationships disclosure. Respondents were generally neutral about framing (U.S.: 44%, Netherlands: 48%), yet many held private 23%, 28%) public 33%, 24%) Public frames associated users disclosure comfort. messaging uptake could improve by understanding when their use as or matter.

Language: Английский

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