Recent Publications - HIV

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 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: 

Strengths, Weaknesses, Opportunities and Challenges for Long Acting Injectable Therapies: Insights for applications in HIV therapy

Date: 
8/1/16
Citation: 

Owen A, Rannard S. Strengths, weaknesses, opportunities and challenges for long acting injectable therapies: Insights for applications in HIV therapy. Adv Drug Deliv Rev. 2016;103:144-156. doi:10.1016/j.addr.2016.02.003. PMID: 26916628; PMCID: PMC4935562.

Many terms have been utilised to describe the LA approach and standardisation would be beneficial.  Ultimately, definitions will depend upon specific indications and routes of delivery.  This review focuses upon the critical importance of potency in achieving the LA outcome for injectable formulations and explores established and emerging technologies that have been employed across indications.

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]. 

Potential Clinical and Economic Value of Long-Acting Preexposure Prophylaxis for South African Women at High-Risk for HIV Infection

Date: 
5/15/16
Citation: 

Walensky RP, Jacobsen MM, Bekker LG, et al. Potential Clinical and Economic Value of Long-Acting Preexposure Prophylaxis for South African Women at High-Risk for HIV Infection. J Infect Dis. 2016;213(10):1523-1531. doi:10.1093/infdis/jiv523. PMID: 26681778; PMCID: PMC4837902.

For young South African women at risk for human immunodeficiency virus (HIV) infection, preexposure prophylaxis (PrEP) is one of the few effective prevention options available. Long-acting injectable PrEP, which is in development, may be associated with greater adherence, compared with that for existing standard oral PrEP formulations, but its likely clinical benefits and additional costs are unknown.

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.

Health Topics: 

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.

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: 

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