scholarly journals Long-Acting Injectable Antiretroviral Agents for HIV Treatment and Prevention

2021 ◽  
Vol 53 ◽  
Author(s):  
Yeon-Sook Kim
Keyword(s):  
Hiv Treatment ◽  
Antiretroviral Agents ◽  
Treatment And Prevention ◽  
Long Acting

scholarly journals The Promise of Improved Adherence With Long-Acting Antiretroviral Therapy: What Are the Data?

2021 ◽  
Vol 20 ◽  
pp. 232595822110090
Author(s):  
Kimberly K. Scarsi ◽  
Susan Swindells
Keyword(s):  
Medication Adherence ◽  
Antiretroviral Therapy ◽  
Hiv Treatment ◽  
Virologic Suppression ◽  
Social Barriers ◽  
Treatment And Prevention ◽  
Undetectable Viremia ◽  
Long Acting ◽  
Available Information ◽  
Living With Hiv

As with other chronic conditions, adherence to daily medications remains a challenge for many individuals living with HIV due to structural, behavioral, and social barriers. Unfortunately, high levels of adherence to antiretroviral therapy are required to maintain virologic suppression. Alternative approaches are being explored to decrease the burden of daily pill administration, including long-acting injectable, oral, and implantable products. Phase 3 data support the efficacy of nanoformulated injectable cabotegravir and rilpivirine for HIV treatment in patients with undetectable viremia, but we have yet to learn how this strategy may benefit those with medication adherence challenges. Despite this, the affected community and HIV providers are very interested in exploring the role of long-acting therapies to address some types of barriers to medication adherence. This review summarizes available information about the potential for long-acting therapy to improve adherence for some patients and outlines associated opportunities and challenges with the implementation of long-acting therapy for the treatment and prevention of HIV.

scholarly journals Ultra-long-acting removable drug delivery system for HIV treatment and prevention

2018 ◽  
Vol 9 (1) ◽  
Author(s):  
Martina Kovarova ◽  
S. Rahima Benhabbour ◽  
Ivana Massud ◽  
Rae Ann Spagnuolo ◽  
Brianna Skinner ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Drug Delivery System ◽  
Delivery System ◽  
Hiv Treatment ◽  
Treatment And Prevention ◽  
Long Acting

scholarly journals Extended-Duration MK-8591-Eluting Implant as a Candidate for HIV Treatment and Prevention

2018 ◽  
Vol 62 (10) ◽  
Author(s):  
Stephanie E. Barrett ◽  
Ryan S. Teller ◽  
Seth P. Forster ◽  
Li Li ◽  
Megan A. Mackey ◽  
...  
Keyword(s):  
Health Care Providers ◽  
Single Agent ◽  
Hiv Treatment ◽  
Oral Drug ◽  
Drug Candidate ◽  
Care Providers ◽  
Sustained Drug Release ◽  
Treatment And Prevention ◽  
Extended Duration ◽  
Long Acting

ABSTRACT Regimen adherence remains a major hurdle to the success of daily oral drug regimens for the treatment and prevention of human immunodeficiency virus (HIV) infection. Long-acting drug formulations requiring less-frequent dosing offer an opportunity to improve adherence and allow for more forgiving options with regard to missed doses. The administration of long-acting formulations in a clinical setting enables health care providers to directly track adherence. MK-8591 (4′-ethynyl-2-fluoro-2′-deoxyadenosine [EFdA]) is an investigational nucleoside reverse transcriptase translocation inhibitor (NRTTI) drug candidate under investigation as part of a regimen for HIV treatment, with potential utility as a single agent for preexposure prophylaxis (PrEP). The active triphosphate of MK-8591 (MK-8591-TP) exhibits protracted intracellular persistence and, together with the potency of MK-8591, supports its consideration for extended-duration dosing. Toward this end, drug-eluting implant devices were designed to provide prolonged MK-8591 release in vitro and in vivo. Implants, administered subcutaneously, were studied in rodents and nonhuman primates to establish MK-8591 pharmacokinetics and intracellular levels of MK-8591-TP. These data were evaluated against pharmacokinetic and pharmacodynamic models, as well as data generated in phase 1a (Ph1a) and Ph1b clinical studies with once-weekly oral administration of MK-8591. After a single administration in animals, MK-8591 implants achieved clinically relevant drug exposures and sustained drug release, with plasma levels maintained for greater than 6 months that correspond to efficacious MK-8591-TP levels, resulting in a 1.6-log reduction in viral load. Additional studies of MK-8591 implants for HIV treatment and prevention are warranted.

Long-Acting HIV Drugs for Treatment and Prevention

2019 ◽  
Vol 70 (1) ◽  
pp. 137-150 ◽  
Author(s):  
Roy M. Gulick ◽  
Charles Flexner
Keyword(s):  
Drug Regimen ◽  
Antiretroviral Drugs ◽  
Hiv Treatment ◽  
Phase Iii ◽  
Treatment And Prevention ◽  
Drug Concentrations ◽  
Phase Iii Trials ◽  
Long Acting ◽  
Hiv Drugs ◽  
Exposure Prophylaxis

Antiretroviral drugs have revolutionized the treatment and prevention of HIV infection; however, adherence is critical for sustained efficacy. Current HIV treatment consists of three-drug regimens, and current HIV pre-exposure prophylaxis (PrEP) consists of a two-drug regimen; both generally require adherence to once-daily dosing. Long-acting formulations are useful in the treatment and prevention of other conditions (e.g., contraceptives, antipsychotics) and help promote adherence. Newer long-acting formulations of approved and investigational antiretroviral drugs in existing and newer mechanistic classes are under study for HIV treatment and prevention, including some phase III trials. Although long-acting antiretroviral drugs hold promise, some clinical challenges exist, including managing side effects, drug-drug interactions, pregnancy, and long-lasting drug concentrations that could lead to the development of drug resistance. This review aims to summarize currently available information on long-acting antiretroviral drugs for HIV treatment and prevention.

scholarly journals Long-acting injectable antiretrovirals for HIV treatment and prevention

2013 ◽  
Vol 8 (6) ◽  
pp. 565-571 ◽  
Author(s):  
William R. Spreen ◽  
David A. Margolis ◽  
John C. Pottage
Keyword(s):  
Hiv Treatment ◽  
Treatment And Prevention ◽  
Long Acting

Biochemical and Pharmacological Properties of SANORG 34006, a Potent and Long-Acting Synthetic Pentasaccharide

Blood ◽  
1998 ◽  
Vol 91 (11) ◽  
pp. 4197-4205 ◽  
Author(s):  
J.M. Herbert ◽  
J.P. Hérault ◽  
A. Bernat ◽  
R.G.M. van Amsterdam ◽  
J.C. Lormeau ◽  
...  
Keyword(s):  
Thrombin Generation ◽  
Ex Vivo ◽  
Thrombus Formation ◽  
Factor Xa ◽  
Therapeutic Index ◽  
Inhibitory Effect ◽  
Experimental Models ◽  
Treatment And Prevention ◽  
Long Acting

Abstract SANORG 34006 is a new sulfated pentasaccharide obtained by chemical synthesis. It is an analog of the “synthetic pentasaccharide” (SR 90107/ ORG 31540) which represents the antithrombin (AT) binding site of heparin. SANORG 34006 showed a higher affinity to human AT than SR 90107/ORG 31540 (kd = 1.4 ± 0.3 v 48 ± 11 nmol/L), and it is a potent and selective catalyst of the inhibitory effect of AT on factor Xa (1,240 ± 15 anti–factor Xa U/mg v850 ± 27 anti-factor Xa U/mg for SR 90107/ORG 31540). In vitro, SANORG 34006 inhibited thrombin generation occurring via both the extrinsic and intrinsic pathway. After intravenous (IV) or subcutaneous (SC) administration to rabbits, SANORG 34006 displayed a long-lasting anti–factor Xa activity and inhibition of thrombin generation (TG) ex vivo. SANORG 34006 was slowly eliminated after IV or SC administration to rats, rabbits, and baboons, showed exceptionally long half-lives (between 9.2 hours in rats and 61.9 hours in baboons), and revealed an SC bioavailability near 100%. SANORG 34006 displayed antithrombotic activity by virtue of its potentiation of the anti–factor Xa activity of AT. It strongly inhibited thrombus formation in experimental models of thromboplastin/stasis-induced venous thrombosis in rats (IV) and rabbits (SC) (ED50values = 40.0 ± 3.4 and 105.0 ± 9.4 nmol/kg, respectively). The duration of its antithrombotic effects closely paralleled the ex vivo anti–factor Xa activity. SANORG 34006 enhanced rt-PA–induced thrombolysis and inhibited accretion of125I-fibrinogen onto a preformed thrombus in the rabbit jugular vein suggesting that concomitant use of SANORG 34006 during rt-PA therapy might be helpful in facilitating thrombolysis and preventing fibrin accretion onto the thrombus under lysis. Contrary to standard heparin, SANORG 34006 did not enhance bleeding in a rabbit ear incision model at a dose that equals 10 times the antithrombotic ED50 in this species and, therefore, exhibited a favorable therapeutic index. We suggest that SANORG 34006 is a promising compound in the treatment and prevention of various thrombotic diseases.

scholarly journals SimpactCyan 1.0: An Open-source Simulator for Individual-Based Models in HIV Epidemiology with R and Python Interfaces

2018 ◽  
Author(s):  
Jori Liesenborgs ◽  
Diana M Hendrickx ◽  
Elise Kuylen ◽  
David Niyukuri ◽  
Niel Hens ◽  
...  
Keyword(s):  
Open Source ◽  
Hiv Infections ◽  
Hiv Treatment ◽  
Model Parameters ◽  
Eligibility Criteria ◽  
Hiv Epidemiology ◽  
Treatment And Prevention ◽  
Individual Based Models ◽  
Prevention Programmes ◽  
The Impact

ABSTRACTSimpactCyan is an open-source simulator for individual-based models in HIV epidemiology. Its core algorithm is written in C++ for computational efficiency, while the R and Python interfaces aim to make the tool accessible to the fast-growing community of R and Python users. Transmission, treatment and prevention of HIV infections in dynamic sexual networks are simulated by discrete events. A generic “intervention” event allows model parameters to be changed over time, and can be used to model medical and behavioural HIV prevention programmes. First, we describe a more efficient variant of the modified Next Reaction Method that drives our continuous-time simulator. Next, we outline key built-in features and assumptions of individual-based models formulated in SimpactCyan, and provide code snippets for how to formulate, execute and analyse models in SimpactCyan through its R and Python interfaces. Lastly, we give two examples of applications in HIV epidemiology: the first demonstrates how the software can be used to estimate the impact of progressive changes to the eligibility criteria for HIV treatment on HIV incidence. The second example illustrates the use of SimpactCyan as a data-generating tool for assessing the performance of a phylodynamic inference framework.

scholarly journals SWTICH DE ESQUEMAS ANTIRRETROVIRAIS DURANTE A PANDEMIA DE COVID-19 EM UM CENTRO DE REFERÊNCIA DA AMÉRICA LATINA

RAHIS ◽  
2021 ◽  
Vol 18 (4) ◽  
pp. 168-169
Author(s):  
Dirce Inês Silva ◽  
Isabela Estrela Santos ◽  
Jaqueline Xavier Oliveira
Keyword(s):  
Research Society ◽  
Hiv Treatment ◽  
Services Research ◽  
Prevention Services ◽  
Treatment And Prevention ◽  
The Social ◽  
America Latina ◽  
Terapia Antirretroviral ◽  
The Impact ◽  
Brazilian Journal

INTRODUÇÃO : O tratamento da infecção pelo vírus da imunodeficiência humana (HIV) é realizado por meio da terapia antirretroviral (TARV) e vem apresentando avanços importantes no decorrer dos anos. Ocorreu a introdução de novas drogas e classes que ampliaram de modo significativo as opções para o tratamento da infecção pelo HIV-1. Existem razões para a troca (Swtich) da TARV, são eles : manutenção da supressão viral, resistência, probabilidade de maior adesão ao tratamento, eventos adversos, interações medicamentosas (1). Durante a pandemia de Covid-19 que vivenciamos desde março de 2020 no Brasil muitas dificuldades ocorreram nos serviços de saúde, principalmente para as pessoas que vivem com HIV como : acesso aos serviços, diagnóstico, tratamento e acompanhamento (2.3). OBJETIVO: Avaliar a prevalência de trocas de esquemas em um centro de referência da América Latina no período de Janeiro de 2020 a 31 de Julho de 2021.METODOLOGIA : Realizamos um estudo transversal no período de 2020 a 2021 , utilizando o sistema de informação : Sistema de Controle Logístico de Medicamentos (SICLOM) do Ministério da Saúde . Os dados foram analisados no Statistical Package for the Social Science(SPSS® ) 22.RESULTADOS : No período do estudo foram detectadas 473 trocas. Em 2020 ocorreram 283 trocas, 83 em mulheres e 200 em homens. E 2021 até o dia 31/07/2021 foram detectadas 190 trocas, 76 ocorreram em mulheres e 114 em homens. As trocas ocorreram devido : resistência, reações adversas, gestação , tratamento concomitante da tuberculose e simplificação do tratamento ( Figura 1 e 2)).   Figura 1 – Ocorências de Swtich de esquemas antirretroviraisFigura 2- Razões de Trocas de Esquemas Antiretrovirais CONCLUSÃO : Swtich dos esquemas antirretrovirais em utilização pode ser uma estratégia de simplificação da TARV, melhoria da adesão, e em muitos casos a redução de eventos adversos. O arsenal terapêutico no contexto brasileiro é diversificado permitindo uma troca com segurança e sem risco de perda da eficácia virológica. Sendo uma estratégia para enfrentamento da infecção pelo HIV mesmo em tempos de pandemia do COVID19. REFERÊNCIAS:1-Brites, Carlos. Terapia antirretroviral atual: tendências e desafios. Estratégias de troca (switch) naterapia antirretroviral atual. Brazilian Journal of Infectious DiseaseVol 2 . Nº 1 . Fevereiro 20162- Moura, Maria Lucia Costa de. (2020). Coronavírus e COVID-19. Revista Saúde Coletiva, 53, 10.3- Parente, J. da S.; Azevedo, S. L. de .; Moreira, L. da F. A.; Abreu, L. M. .; Souza, L. V. de. The impact of social isolation on the COVID-19 pandemic on access to HIV treatment and prevention services. Research, Society and Development, [S. l.], v. 10, n. 1, p. e28110111692, 2021.  

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