Recent Publications

Supramolecular nanomedicines through rational design of self-assembling prodrugs

Date: 
4/19/22
Citation: 

Wang H, Monroe M, Leslie F, Flexner C, Cui H. Supramolecular nanomedicines through rational design of self-assembling prodrugs. Trends Pharmacol Sci. 2022 Apr 19:S0165-6147(22)00053-0. doi: 10.1016/j.tips.2022.03.003. Epub ahead of print. PMID: 35459589.

Advancements in the development of nanomaterials have led to the creation of a plethora of functional constructs as drug delivery vehicles to address many dire medical needs. The emerging prodrug strategy provides an alternative solution to create nanomedicines of extreme simplicity by directly using the therapeutic agents as molecular building blocks. This Review outlines different prodrug-based drug delivery systems, highlights the advantages of the prodrug strategy for therapeutic delivery, and demonstrates how combinations of different functionalities - such as stimuli responsiveness,

Tenofovir Alafenamide for HIV Prevention: Review of the Proceedings from the Gates Foundation Long-Acting TAF Product Development Meeting

Date: 
11/1/21
Citation: 

Romano JW, Baum MM, Demkovich ZR, Diana F, Dobard C, Feldman PL, Garcia-Lerma JG, Grattoni A, Gunawardana M, Ho DK, Hope TJ, Massud I, Milad M, Moss JA, Pons-Faudoa FP, Roller S, van der Straten A, Srinivasan S, Veazey RS, Zane D. Tenofovir Alafenamide for HIV Prevention: Review of the Proceedings from the Gates Foundation Long-Acting TAF Product Development Meeting. AIDS Res Hum Retroviruses. 2021 Jun;37(6):409-420. doi: 10.1089/AID.2021.0028. PMID: 33913760; PMCID: PMC8213003.

The ability to successfully develop a safe and effective vaccine for the prevention of HIV infection has proven challenging. Consequently, alternative approaches to HIV infection prevention have been pursued, and there have been a number of successes with differing levels of efficacy. At present, only two oral preexposure prophylaxis (PrEP) products are available,

Health Topics: 

The LAIs Are Coming! Implementation Science Considerations for Long-Acting Injectable Antiretroviral Therapy in the United States: A Scoping Review

Date: 
10/14/21
Citation: 

Kanazawa JT, Saberi P, Sauceda JA, Dubé K. The LAIs Are Coming! Implementation Science Considerations for Long-Acting Injectable Antiretroviral Therapy in the United States: A Scoping Review. AIDS Res Hum Retroviruses. 2021 Feb;37(2):75-88. doi: 10.1089/AID.2020.0126. Epub 2020 Dec 7. PMID: 33176429; PMCID: PMC8020525.

Long-acting injectable antiretroviral therapy (LAI-ART) is one of the latest advancements in HIV control with the potential to overcome oral ART barriers to adherence. The objective of this article is to anticipate and examine implementation considerations for LAI-ART using components of the PRISM model, a Practical, Robust Implementation and Sustainability Model for integrating research findings into practice.

Efficacy, Safety, and Durability of Long-Acting Cabotegravir and Rilpivirine in Adults With Human Immunodeficiency Virus Type 1 Infection: 5-Year Results From the LATTE-2 Study

Date: 
10/4/21
Citation: 

Smith GHR, Henry WK, Podzamczer D, Masiá MDM, Bettacchi CJ, Arasteh K, Jaeger H, Khuong-Josses MA, Montes-Ramírez ML, Stellbrink HJ, Yazdanpanah Y, Richmond GJ, Sutton KC, Zhang F, McCoig CC, St Clair MH, Vandermeulen K, Van Solingen-Ristea R, Smith KY, Margolis DA, Spreen WR. Efficacy, Safety, and Durability of Long-Acting Cabotegravir and Rilpivirine in Adults With Human Immunodeficiency Virus Type 1 Infection: 5-Year Results From the LATTE-2 Study. Open Forum Infect Dis. 2021 Aug 25;8(9):ofab439. doi: 10.1093/ofid/ofab439. PMID: 34557563; PMCID: PMC8454521.

In the Long-Acting Antiretroviral Treatment Enabling Trial 2 (LATTE-2) phase 2b study, long-acting (LA) injectable cabotegravir + rilpivirine dosed every 8 weeks (Q8W) or every 4 weeks (Q4W) demonstrated comparable efficacy with daily oral antiretroviral therapy (ART) through 96 weeks in ART-naive adults with human immunodeficiency virus type 1 (HIV-1). Here we report efficacy, tolerability, and safety of cabotegravir + rilpivirine LA over approximately 5 years.

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Population pharmacokinetics of the rilpivirine long-acting formulation after intramuscular dosing in healthy subjects and people living with HIV

Date: 
9/12/21
Citation: 

Neyens M, Crauwels HM, Perez-Ruixo JJ, Rossenu S. Population pharmacokinetics of the rilpivirine long-acting formulation after intramuscular dosing in healthy subjects and people living with HIV. J Antimicrob Chemother. 2021 Sep 12:dkab338. doi: 10.1093/jac/dkab338. Epub ahead of print. PMID: 34510179.

Rich and sparse rilpivirine plasma concentration data were obtained from seven clinical studies. In total, 18 261 rilpivirine samples were collected from 986 subjects (131 healthy subjects from Phase I studies and 855 people living with HIV from Phase IIb/III studies). Doses ranged from 300 to 1200 mg, as single-dose or multiple-dose regimens (every 4 or 8 weeks).

Health Topics: 

"Lighten This Burden of Ours": Acceptability and Preferences Regarding Injectable Antiretroviral Treatment Among Adults and Youth Living With HIV in Coastal Kenya

Date: 
6/29/21
Citation: 

Simoni JM, Beima-Sofie K, Wanje G, Mohamed ZH, Tapia K, McClelland RS, Ho RJY, Collier AC, Graham SM. "Lighten This Burden of Ours": Acceptability and Preferences Regarding Injectable Antiretroviral Treatment Among Adults and Youth Living With HIV in Coastal Kenya. J Int Assoc Provid AIDS Care. 2021 Jan-Dec;20:23259582211000517. doi: 10.1177/23259582211000517. PMID: 33685272; PMCID: PMC7952847.

Since 2010, the global scale-up of antiretroviral therapy (ART) has contributed to a 50% decline in global annual deaths from AIDS-related illness, from a peak of 1.9 million in 2005 to 940,000 in 2017, highlighting the importance of ART in reducing morbidity and mortality.1 However, UNAIDS has estimated that only 77% of diagnosed persons living with HIV are accessing ART, and only 82% of patients on ART have suppressed viral loads,2 suggesting there is room for improvement in adherence.

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

Date: 
6/29/21
Citation: 

Scarsi KK, Swindells S. The Promise of Improved Adherence With Long-Acting Antiretroviral Therapy: What Are the Data? J Int Assoc Provid AIDS Care. 2021 Jan-Dec;20:23259582211009011. doi: 10.1177/23259582211009011. PMID: 33902356; PMCID: PMC8082990.

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.

Health Topics: 

Identification of a novel long-acting 4’-modified nucleoside reverse transcriptase inhibitor against HBV

Date: 
3/19/21
Citation: 

Higashi-Kuwata N, Hayashi S, Kumamoto H, Ogata-Aoki H, Das D, Venzon D, Hattori SI, Bulut H, Hashimoto M, Otagiri M, Takamune N, Kishimoto N, Davis D, Misumi S, Kakuni M, Tanaka Y, Mitsuya H. Identification of a novel long-acting 4'-modified nucleoside reverse transcriptase inhibitor against HBV. J Hepatol. 2020 Dec 14:S0168-8278(20)33843-5. doi: 10.1016/j.jhep.2020.12.006. Epub ahead of print. PMID: 33333207.

Although there are currently effective treatment options for HBV, treatment-resistant variants and the need for lifelong therapy pose a significant challenge. Therefore, the development of new treatment options is crucial to improve out-comes and quality of life. Herein, this study reports preclinical evidence showing that the anti-HBV agent, E-CFCP, has potent activity against wild-type and treatment-resistant variants. In addition, once-weekly oral dosing may be possible,which is preferable to the current daily dosing regimens.

Predictors of HIV-1 virologic failure to long-acting cabotegravir and rilpivirine: a multivariable analysis across three phase 3 studies

Date: 
3/18/21
Citation: 

Cutrell AG, Schapiro JM, Perno CF, Kuritzkes DR, Quercia R, Patel P, Polli JW, Dorey D, Wang Y, Wu S, van Eygen V, Crauwels H, Ford SL, Baker M, Talarico CL, Clair MST, Jeffrey J, White CT, Vanveggel S, Vandermeulen K, Margolis DA, Aboud M, Spreen WR, van Lunzen J. Predictors of HIV-1 virologic failure to long-acting cabotegravir and rilpivirine: a multivariable analysis across three phase 3 studies. AIDS. 2021 Mar 16. doi: 10.1097/QAD.0000000000002883. Epub ahead of print. PMID: 33730748.

Efficacy and safety of long-acting (LA) cabotegravir (CAB) and rilpivirine (RPV) dosed intramuscularly every 4 or 8 weeks has been demonstrated in three Phase 3 trials. Here, factors associated with virologic failure at Week 48 were evaluated post hoc.

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Long-acting cabotegravir and rilpivirine dosed every 2 months in adults with HIV-1 infection (ATLAS-2M), 48-week results: a randomised, multicentre, open-label, phase 3b, non-inferiority study

Date: 
12/9/20
Citation: 

Overton ET, Richmond G, Rizzardini G, Jaeger H, Orrell C, Nagimova F, Bredeek F, Deltoro MG, Swindells S, Andrade-Villanueva JF, Wong A, Khuong-Josses M, Solingen-Ristea RV, Eygen VV, Crauwels H, Ford S, Talarico C, Benn P, Wang Y, Hudson KJ, Chounta V, Cutrell A, Patel P, Shaefer M, Margolis DA, Smith KY, Vanveggel S, Spreen W. Long-acting cabotegravir and rilpivirine dosed every 2 months in adults with HIV-1 infection (ATLAS-2M), 48-week results: a randomised, multicentre, open-label, phase 3b, non-inferiority study, The Lancet, 2020, ISSN 0140-6736.

Phase 3 clinical studies showed non-inferiority of long-acting intramuscular cabotegravir and rilpivirine dosed every 4 weeks to oral antiretroviral therapy. Important phase 2 results of every 8 weeks dosing, and supportive modelling, underpin further evaluation of every 8 weeks dosing in this trial, which has the potential to offer greater convenience. Our objective was to compare the week 48 antiviral efficacy of cabotegravir plus rilpivirine long-acting dosed every 8 weeks with that of every 4 weeks dosing. 

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