Recent Publications

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

Long-Acting Injectable Preexposure Prophylaxis for HIV Prevention in South Africa: Is There a Will and a Way?

Date: 
5/15/16
Citation: 

Landovitz RJ, Grinsztejn B. Long-Acting Injectable Preexposure Prophylaxis for HIV Prevention in South Africa: Is There a Will and a Way?. J Infect Dis. 2016;213(10):1519-1520. doi:10.1093/infdis/jiv524. PMID: 26681779.

Human immunodeficiency virus (HIV) antiretroviral therapy (ART) use results in substantial improvements in HIV-related morbidity and mortality [1, 2] and leads to dramatic reductions in sexual transmission of HIV among heterosexual serodiscordant couples when ART suppresses HIV viremia in the infected partner [3]. 

Nanodrug formulations to enhance HIV drug exposure in lymphoid tissues and cells: clinical significance and potential impact on treatment and eradication of HIV/AIDS

Date: 
2/9/16
Citation: 

Shao J, Kraft JC, Li B, et al. Nanodrug formulations to enhance HIV drug exposure in lymphoid tissues and cells: clinical significance and potential impact on treatment and eradication of HIV/AIDS. Nanomedicine (Lond). 2016;11(5):545-564. doi:10.2217/nnm.16.1. PMID: 26892323; PMCID: PMC4910949.

Although oral combination antiretroviral therapy effectively clears plasma HIV, patients on oral drugs exhibit much lower drug concentrations in lymph nodes than blood. This drug insufficiency is linked to residual HIV in cells of lymph nodes. While nanoformulations improve drug solubility, safety and delivery, most HIV nanoformulations are intended to extend plasma levels.

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New perspectives on nanotechnology and antiretroviral drugs: a ‘small’ solution for a big promise in HIV treatment?

Date: 
3/27/16
Citation: 

Corsi F, Fiandra L, Rizzardini G. New perspectives on nanotechnology and antiretroviral drugs: a 'small' solution for a big promise in HIV treatment?. AIDS. 2016;30(6):963-964. doi:10.1097/QAD.0000000000001026. PMID: 26807964.

In this issue, Li et al.[1] present a well designed multidisciplinary study, aimed to demonstrate the potential benefit of a multifunctional polymeric nanodevice for delivering HIV treatment.

Co-delivery of HIV-1 entry inhibitor and NNRTI shuttled by nanoparticles: cocktail therapeutic strategy for antiviral therapy

Date: 
3/27/16
Citation: 

Li W, Yu F, Wang Q, et al. Co-delivery of HIV-1 entry inhibitor and nonnucleoside reverse transcriptase inhibitor shuttled by nanoparticles: cocktail therapeutic strategy for antiviral therapy. AIDS. 2016;30(6):827-838. doi:10.1097/QAD.0000000000000971. PMID: 26595538.

OBJECTIVES: 
Traditionally, the antiviral efficacy of classic cocktail therapy is significantly limited by the distinct pharmacokinetic profiles of partner therapeutics that lead to inconsistent in-vivo biodistribution.

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The mixed lineage kinase-3 inhibitor URMC-099 improves therapeutic outcomes for long-acting antiretroviral therapy

Date: 
1/15/16
Citation: 

Zhang G, Guo D, Dash PK, et al. The mixed lineage kinase-3 inhibitor URMC-099 improves therapeutic outcomes for long-acting antiretroviral therapy. Nanomedicine. 2016;12(1):109-122. doi:10.1016/j.nano.2015.09.009. PMID: 26472049; PMCID: PMC4728028.

During studies to extend the half-life of crystalline nanoformulated antiretroviral therapy (nanoART) the mixed lineage kinase-3 inhibitor URMC-099, developed as an adjunctive neuroprotective agent was shown to facilitate antiviral responses.

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In Silico Dose Prediction for Long-Acting Rilpivirine and Cabotegravir Administration to Children and Adolescents

Date: 
5/24/17
Citation: 

Rajoli RKR, Back DJ, Rannard S, et al. In Silico Dose Prediction for Long-Acting Rilpivirine and Cabotegravir Administration to Children and Adolescents. Clin Pharmacokinet. 2018;57(2):255-266. doi:10.1007/s40262-017-0557-x. PMID: 28540638; PMCID: PMC5701864.

Long-acting injectable antiretrovirals represent a pharmacological alternative to oral formulations and an innovative clinical option to address adherence and reduce drug costs. Clinical studies in children and adolescents are characterised by ethical and logistic barriers complicating the identification of dose optimisation.

Long-acting intramuscular cabotegravir and rilpivirine in adults with HIV-1 infection (LATTE-2): 96-week results of a randomised, open-label, phase 2b, non-inferiority trial

Date: 
9/23/17
Citation: 

Margolis DA, Gonzalez-Garcia J, Stellbrink HJ, et al. Long-acting intramuscular cabotegravir and rilpivirine in adults with HIV-1 infection (LATTE-2): 96-week results of a randomised, open-label, phase 2b, non-inferiority trial. Lancet. 2017;390(10101):1499-1510. doi:10.1016/S0140-6736(17)31917-7. PMID: 28750935.

The two-drug combination of all-injectable, long-acting cabotegravir plus rilpivirine every 4 weeks or every 8 weeks was as effective as daily three-drug oral therapy at maintaining HIV-1 viral suppression through 96 weeks and was well accepted and tolerated.

Drug delivery strategies and systems for HIV/AIDS pre-exposure prophylaxis and treatment

Date: 
12/10/15
Citation: 

Nelson AG, Zhang X, Ganapathi U, et al. Drug delivery strategies and systems for HIV/AIDS pre-exposure prophylaxis and treatment. J Control Release. 2015;219:669-680. doi:10.1016/j.jconrel.2015.08.042. PMID: 26315816; PMCID: PMC4879940.

The year 2016 will mark an important milestone - the 35th anniversary of the first reported cases of HIV/AIDS. Antiretroviral Therapy (ART) including Highly Active Antiretroviral Therapy (HAART) drug regimens is widely considered to be one of the greatest achievements in therapeutic drug research having transformed HIV infection into a chronically managed disease. Unfortunately, the lack of widespread preventive measures and the inability to eradicate HIV from infected cells highlight the significant challenges remaining today.

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Long-acting combination anti-HIV drug suspension enhances and sustains higher drug levels in lymph node cells than in blood cells and plasma

Date: 
3/27/17
Citation: 

Kraft JC, McConnachie LA, Koehn J, et al. Long-acting combination anti-HIV drug suspension enhances and sustains higher drug levels in lymph node cells than in blood cells and plasma. AIDS. 2017;31(6):765-770. doi:10.1097/QAD.0000000000001405. PMID: 28099191; PMCID: PMC5345888.

Objective:
To determine if a combination of anti-HIV drugs-tenofovir (TFV), lopinavir (LPV), and ritonavir (RTV)-in a lipid-stabilized nanosuspension (called TLC-ART101) could enhance and sustain intracellular drug levels and exposures in lymph node and blood cells above those in plasma.

Design:
Four macaques were given a single dose of TLC-ART101 subcutaneously. Drug concentrations in plasma and mononuclear cells of the blood (PBMCs) and lymph nodes (LNMCs) were analyzed using a validated combination LC-MS/MS assay.

Health Topics: 

Systems Approach to Targeted and Long-acting HIV/AIDS Therapy

Date: 
12/5/15
Citation: 

Ho RJ, Yu J, Li B, et al. Systems Approach to targeted and long-acting HIV/AIDS therapy. Drug Deliv Transl Res. 2015;5(6):531-539. doi:10.1007/s13346-015-0254-y. PMID: 26315144; PMCID: PMC4826474.

ABSTRACT
Medication adherence and insufficient drug levels are central to HIV/AIDS disease progression. Recently, Fletcher et al. confirmed that HIV patients on oral antiretroviral therapy had lower intracellular drug concentrations in lymph nodes than in blood. For instance, in the same patient, multiple lymph node drug concentrations were as much as 99 % lower than in blood. This study built upon our previous finding that HIV patients taking oral indinavir had 3-fold lower mononuclear cell drug concentrations in lymph nodes than in blood. As a result, an association between insufficient lymph node drug concentrations in cells and persistent viral replication has now been validated. Lymph node cells, particularly CD4 T lymphocytes, host HIV infection and persistence; CD4 T cell depletion in blood correlates with AIDS progression. With established drug targets to overcome drug insufficiency in lymphoid cells and tissues, we have developed and employed a "Systems Approach" to engineer multi-drug-incorporated particles for HIV treatment.
 
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