Recent Publications - No name

A long-acting formulation of the integrase inhibitor raltegravir protects humanized BLT mice from repeated high-dose vaginal HIV challenges

Date: 
3/21/16
Citation: 

Kovarova M, Swanson MD, Sanchez RI, et al. A long-acting formulation of the integrase inhibitor raltegravir protects humanized BLT mice from repeated high-dose vaginal HIV challenges. J Antimicrob Chemother. 2016 Jun;71(6):1586-96. doi: 10.1093/jac/dkw042. Epub 2016 Mar 21. PMID: 27002074; PMCID: PMC4867102.

Objectives:
Pre-exposure prophylaxis (PrEP) using antiretroviral drugs (ARVs) has been shown to reduce HIV transmission in people at high risk of HIV infection. Adherence to PrEP strongly correlates with the level of HIV protection. Long-acting injectable ARVs provide sustained systemic drug exposures over many weeks and can improve adherence due to infrequent parenteral administration. Here, we evaluated a new long-acting formulation of raltegravir for prevention of vaginal HIV transmission.

Antiretroviral Drugs-Loaded Nanoparticles Fabricated by Dispersion Polymerization with Potential for HIV/AIDS Treatment

Date: 
3/20/16
Citation: 

Ogunwuyi O, Kumari N, Smith KA, et al. Antiretroviral Drugs-Loaded Nanoparticles Fabricated by Dispersion Polymerization with Potential for HIV/AIDS Treatment. Infect Dis (Auckl). 2016;9:21-32. Published 2016 Mar 20. doi:10.4137/IDRT.S38108. PMID: 27013886; PMCID: PMC4803317.

Highly active antiretroviral (ARV) therapy (HAART) for chronic suppression of HIV replication has revolutionized the treatment of HIV/AIDS. HAART is no panacea; treatments must be maintained for life. Although great progress has been made in ARV therapy, HIV continues to replicate in anatomical and intracellular sites where ARV drugs have restricted access.

Health Topics: 

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.

Health Topics: 

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.

Health Topics: 

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.

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.
 
Health Topics: 

Regulatory challenges in developing long-acting antiretrovirals for treatment and prevention of HIV infection

Date: 
7/1/15
Citation: 

Arya V, Au S, Belew Y, Miele P, Struble K. Regulatory challenges in developing long-acting antiretrovirals for treatment and prevention of HIV infection. Curr Opin HIV AIDS. 2015 Jul;10(4):278-81. doi: 10.1097/COH.0000000000000163. PMID: 26049954.

Despite advances in drug development that have reduced ARV dosing to once daily, suboptimal drug adherence remains an obstacle to successful HIV treatment. Further, large randomized trials of once daily oral ARVs for preexposure prophylaxis (PrEP) have shown that drug adherence correlates strongly with prophylactic effect and study outcomes. Thus, the prospect of developing long-acting ARVs, which may mitigate drug adherence issues, has attracted considerable attention lately.

Health Topics: 

Long-acting HIV Drugs Advanced to Overcome Adherence Challenge

Date: 
4/7/14
Citation: 

Dolgin E. Long-acting HIV Drugs Advanced to Overcome Adherence Challenge Nat Med. 2014 Apr 7;20(4):323-4. PMID: 24710366.

The results from a particular drug trial presented here last month at the annual Conference on Retroviruses and Opportunistic Infections (CROI) may not have seemed particularly noteworthy. It simply showed that two pills performed as well as another combination of medicines. But the antiretroviral agents tested in the trial were not your ordinary drugs.

Health Topics: 

Long-acting injectable antiretrovirals for HIV treatment and prevention

Date: 
11/15/13
Citation: 

Spreen WR, Margolis DA, & Pottage JC Jr. Long-acting injectable antiretrovirals for HIV treatment and prevention. Curr Opin HIV AIDS. 2013 Nov;8(6):565-71. PMID: 24100877; PMCID: PMC3815009.

Investigational long-acting injectable nanoformulations of rilpivirine and GSK1265744 are clinical-stage development candidates. 

Health Topics: 

Long-acting injectable atovaquone nanomedicines for malaria prophylaxis

Citation: 

Bakshi RP, Tatham LM, Savage AC, et al. Long-acting injectable atovaquone nanomedicines for malaria prophylaxis. Nat Commun. 2018;9(1):315. Published 2018 Jan 22. doi:10.1038/s41467-017-02603-z. PMID: 29358624, PMCID: PMC5778127.

Chemoprophylaxis is currently the best available prevention from malaria, but its efficacy is compromised by non-adherence to medication. Here we develop a long-acting injectable formulation of atovaquone solid drug nanoparticles that confers long-lived prophylaxis against Plasmodium berghei ANKA malaria in C57BL/6 mice. Protection is obtained at plasma concentrations above 200 ng ml-1 and is causal, attributable to drug activity against liver stage parasites

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