Recent Publications

The latest research and clinical studies being done in long-acting, extended release drugs for HIV and TB.

The Invisible Product: Preferences for Sustained-Release, Long-Acting Pre-exposure Prophylaxis to HIV Among South African Youth

Date: 
3/14/19
Citation: 

Montgomery ET, Atujuna M, Krogstad E, et al. The Invisible Product: Preferences for Sustained-Release, Long-Acting Pre-exposure Prophylaxis to HIV Among South African Youth. J Acquir Immune Defic Syndr. 2019 Apr 15;80(5):542-550. doi: 10.1097/QAI.0000000000001960. PMID: 30865050; PMCID: PMC6426447.

Long-acting injectable and implantable approaches aim to overcome some of the documented challenges with uptake and adherence to current HIV prevention methods. Youth are a key end-user population for these methods. We used qualitative methods to examine product attributes and preferences for current and future long-acting HIV prevention approaches.

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

Date: 
2/13/19
Citation: 

Kovarova M, Benhabbour SR, Massud I, et al. Ultra-long-acting removable drug delivery system for HIV treatment and prevention. Nat Commun. 2018;9(1):4156. Published 2018 Oct 8. doi:10.1038/s41467-018-06490-w. PMID: 30297889; PMCID: PMC6175887.

Non-adherence to medication is an important health care problem, especially in the treatment of chronic conditions. Injectable long-acting (LA) formulations of antiretrovirals (ARVs) represent a viable alternative to improve adherence to HIV/AIDS treatment and prevention. However, the LA-ARV formulations currently in clinical trials cannot be removed after administration even if adverse events occur. Here we show an ultra-LA removable system that delivers drug for up to 9 months and can be safely removed to stop drug delivery.

Nanoencapsulation introduces long-acting phenomenon to tenofovir alafenamide and emtricitabine drug combination: A comparative pre-exposure prophylaxis efficacy study against HIV-1 vaginal transmission

Date: 
1/28/19
Citation: 

Mandal S, Kang G, Prathipati PK. et al. Nanoencapsulation introduces long-acting phenomenon to tenofovir alafenamide and emtricitabine drug combination: A comparative pre-exposure prophylaxis efficacy study against HIV-1 vaginal transmission. J Control Release. 2019 Jan 28;294:216-225. doi: 10.1016/j.jconrel.2018.12.027. Epub 2018 Dec 18. PMID: 30576746; PMCID: PMC6339842.

Abstract
Daily oral antiretroviral (ARV) drugs for pre-exposure prophylaxis (PrEP) has proven efficacy for diverse groups of high-risk individuals. However, daily dosing regimen has augmented non-adherence. These experiments comparatively investigated the long-acting (LA) PrEP potency of subcutaneous (SubQ) administrated tenofovir alafenamide (TAF) and emtricitabine (FTC) loaded nanoparticles (NPs) to solution in humanized (hu) mice.

Predicting drug-drug interactions between rifampicin and long-acting cabotegravir and rilpivirine using PBPK modelling

Date: 
12/19/18
Citation: 

Rajoli RKR, Curley P, Chiong J, et al. Predicting drug-drug interactions between rifampicin and long-acting cabotegravir and rilpivirine using PBPK modelling. J Infect Dis. 2019 May 5;219(11):1735-1742. doi: 10.1093/infdis/jiy726. PMID: 30566691; PMCID: PMC6500558.

Cabotegravir and rilpivirine are two long-acting (LA) ARVs that can be administered intramuscularly (IM); their interaction with rifampicin, a first-line anti-TB agent, has not been investigated. The aim of this study was to simulate and predict DDIs between these LA ARV agents and rifampicin using PBPK modelling.

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

Date: 
11/12/18
Citation: 

Kovarova M, Benhabbour SR, Massud I, Spagnuolo RA, Skinner B, Baker CE, Sykes C, Mollan KR, Kashuba ADM, Garcia-Lerma JG, Mumper RJ, Garcia JV. Ultra-long-acting removable drug delivery system for HIV treatment and prevention. Nat Commun. 2018 Oct 8;9(1):4156.  doi: 10.1038/s41467-018-06490-w. PMID: 30297889; PMCID: PMC6175887.

Abstract
Non-adherence to medication is an important health care problem, especially in the treatment of chronic conditions. Injectable long-acting (LA) formulations of antiretrovirals (ARVs) represent a viable alternative to improve adherence to HIV/AIDS treatment and prevention. However, the LA-ARV formulations currently in clinical trials cannot be removed after administration even if adverse events occur. Here we show an ultra-LA removable system that delivers drug for up to 9 months and can be safely removed to stop drug delivery. 

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

Date: 
10/1/18
Citation: 

Barrett SE, Teller RS, Forster SP, et al. Extended-Duration MK-8591-Eluting Implant as a Candidate for HIV Treatment and Prevention. Antimicrob Agents Chemother. 2018 Sep 24;62(10). PMID: 30012772; PMCID: PMC6153840.

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.

Modelling the long-acting administration of anti-tuberculosis agents using PBPK: a proof of concept study

Date: 
8/17/18
Citation: 

Rajoli RKR, PodanyAT, Moss DM, et al. Modelling the long-acting administration of anti-tuberculosis agents using PBPK: a proof of concept study. Int J Tuberc Lung Dis. 2018 Aug 1;22(8):937-944. PMID: 29991405; PMCID: PMC6166436.

SETTING:
Anti-tuberculosis formulations necessitate uninterrupted treatment to cure tuberculosis (TB), but are characterised by suboptimal adherence, which jeopardises therapeutic efficacy. Long-acting injectable (LAI) formulations or implants could address these associated issues.

OBJECTIVE:
niazid, rifapentine, bedaquiline and delamanid—in adults for treatment for latent tuberculous infection (LTBI).

Long-acting injectables for tuberculosis prophylaxis and treatment: is now the time?

Date: 
8/17/18
Citation: 

Dooley KE. Long-acting injectables for tuberculosis prophylaxis and treatment: is now the time? Int J Tuberc Lung Dis. 2018 Aug 1;22(8):833-34. DOI: https://doi.org/10.5588/ijtld.18.0411.

Tuberculosis (TB) is a wily and enduring foe, responsible for 1 billion deaths in the last 200 years. With the introduction of antibiotics active against Mycobacterium tuberculosis in the 1950s, TB disease could finally be cured with multidrug therapy. TB drugs must still be given for months, generally via directly observed therapy, which is intrusive, expensive, and inconvenient.

Health Topics: 

Recent developments of nanotherapeutics for targeted and long-acting, combination HIV chemotherapy

Date: 
8/14/18
Citation: 

Gao Y, Kraft JC, Yu D, Ho RJY.  Recent developments of nanotherapeutics for targeted and long-acting, combination HIV chemotherapy. Eur J Pharm Biopharm. 2019 May;138:75-91. doi: 10.1016/j.ejpb.2018.04.014. Epub 2018 Apr 17. PMID: 29678735; PMCID: PMC6482852.

Combination antiretroviral therapy (cART) given orally has transformed HIV from a terminal illness to a manageable chronic disease. Yet despite the recent development of newer and more potent drugs for cART and suppression of virus in blood to undetectable levels, residual virus remains in tissues.

Mechanism-based pharmacokinetic (MBPK) models describe the complex plasma kinetics of three antiretrovirals delivered by a long-acting anti-HIV drug combination nanoparticle formulation.

Date: 
2/12/18
Citation: 

Kraft JC, Treuting PM, Ho RJY. Mechanism-based pharmacokinetic (MBPK) models describe the complex plasma kinetics of three antiretrovirals delivered by a long-acting anti-HIV drug combination nanoparticle formulation. J Control Release. 2018 Apr 10;275:229-241. doi: 10.1016/j.jconrel.2018.02.003. Epub 2018 Feb 10. PMID: 29432823; PMCID: PMC5878144.

Existing oral antiretroviral (ARV) agents have been shown in human studies to exhibit limited lymph node penetration and lymphatic drug insufficiency. As lymph nodes are a reservoir of HIV, it is critical to deliver and sustain effective levels of ARV combinations in these tissues. To overcome lymph node drug insufficiency of oral combination ARV therapy (cART), we developed and reported a long-acting and lymphocyte-targeting injectable that contains three ARVs-hydrophobic lopinavir (LPV) and ritonavir (RTV), and hydrophilic tenofovir (TFV)-stabilized by lipid excipients in a nanosuspension.

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