LA/ER Injectable Therapy

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.

"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.

A year-long extended release nanoformulated cabotegravir prodrug

Date: 
8/15/20
Citation: 

Kulkarni TA, Bade AN, Sillman B, et al. A year-long extended release nanoformulated cabotegravir prodrug. Nat Mater. 2020;19(8):910-920. doi:10.1038/s41563-020-0674-z

Long-acting cabotegravir (CAB) extends antiretroviral drug administration from daily to monthly. However, dosing volumes, injection site reactions and health-care oversight are obstacles towards a broad usage. The creation of poloxamer-coated hydrophobic and lipophilic CAB prodrugs with controlled hydrolysis and tissue penetrance can overcome these obstacles. To such ends, fatty acid ester CAB nanocrystal prodrugs with 14, 18 and 22 added carbon chains were encased in biocompatible surfactants named NMCAB, NM2CAB and NM3CAB and tested for drug release, activation, cytotoxicity, antiretroviral activities, pharmacokinetics and biodistribution.

Pharmacokinetics, Safety and Tolerability of Long-Acting Parenteral Intramuscular Injection Formulations of Doravirine

Date: 
6/5/20
Citation: 

Yee KL, Mittal S, Fan L, et al. Pharmacokinetics, safety and tolerability of long-acting parenteral intramuscular injection formulations of doravirine [published online ahead of print, 2020 Jun 5]. J Clin Pharm Ther. 2020;10.1111/jcpt.13182. doi:10.1111/jcpt.13182. PMID: 32501541.

Doravirine is a non-nucleoside reverse transcriptase inhibitor indicated for the treatment of human immunodeficiency virus (HIV)-1 infection. This phase 1 study in healthy adults investigated the pharmacokinetics, safety and tolerability of long-acting parenteral (LAP) microsuspension formulations of doravirine administered as an intramuscular (IM) injection.

The Potential Impact of Long-Acting Cabotegravir for HIV Prevention in South Africa: A Mathematical Modelling Study

Date: 
6/3/20
Citation: 

Smith JA, Garnett GP, Hallett TB. The Potential Impact of Long-Acting Cabotegravir for HIV Prevention in South Africa: A Mathematical Modelling Study. J Infect Dis. 2020 Jun 3. pii: jiaa296. doi: 10.1093/infdis/jiaa296. [Epub ahead of print] PMID: 32492704.

Although effective, some oral pre-exposure prophylaxis (PrEP) users face barriers to adherence using daily pills, which could be reduced by long-acting formulations. Long-acting cabotegravir (CAB LA) is a potential new injectable formulation for HIV PrEP being tested in Phase III trials.

Addressing the global burden of hepatitis B virus while developing long-acting injectables for the prevention and treatment of HIV

Date: 
6/1/20
Citation: 

Bollinger RC, Thio CL, Sulkowski MS, McKenzie-White J, Thomas DL, Flexner C. Addressing the global burden of hepatitis B virus while developing long-acting injectables for the prevention and treatment of HIV. Lancet HIV. 2020 Jun;7(6):e443-e448. doi: 10.1016/S2352-3018(19)30342-X. Epub 2019 Dec 20. PMID: 31870675; PMCID: PMC7376366.

The first long-acting formulations of HIV drugs are undergoing regulatory review for use in maintenance of viral suppression in people with HIV. Although these novel drug formulations could contribute greatly to HIV treatment and prevention efforts, their lack of activity against hepatitis B virus (HBV) could limit their global impact, particularly in populations with high burdens of both HIV and HBV.

Long-acting injectable cabotegravir is highly effective for the prevention of HIV infection in cisgender men and transgender women who have sex with men

Date: 
5/18/20
Citation: 

Long-acting injectable cabotegravir is highly effective for the prevention of HIV infection in cisgender men and transgender women who have sex with men [news release]. HIV Prevention Trials Network; May 18, 2020.

The HIV Prevention Trials Network (HPTN) announced today results from HPTN 083, a global randomized, controlled, double-blind study that compared the safety and efficacy of long-acting injectable cabotegravir (CAB LA) to daily oral tenofovir/emtricitabine (TDF/FTC) (Truvada) for pre-exposure prophylaxis (PrEP). The study showed that CAB LA lowered HIV incidence among cisgender men and transgender women who have sex with men. During a planned review of study data, an independent Data and Safety Monitoring Board (DSMB) recommended that the study results be announced as soon as possible. The study sponsor, the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health, agreed with this recommendation.

A Conjoint Analysis of the Acceptability of Targeted Long-Acting Injectable Antiretroviral Therapy Among Persons Living with HIV in the U.S

Date: 
4/15/20
Citation: 

Simoni JM, Tapia K, Lee SJ, Graham SM, Beima-Sofie K, Mohamed ZH, Christodoulou J, Ho R, Collier AC. A Conjoint Analysis of the Acceptability of Targeted Long-Acting Injectable Antiretroviral Therapy Among Persons Living with HIV in the U.S. AIDS Behav. 2020 Apr;24(4):1226-1236. doi: 10.1007/s10461-019-02701-7. PMID: 31655915; PMCID: PMC7085450.

With long-acting injectable antiretroviral therapy likely to be a treatment option for people living with HIV (PLWH), it is critical to assess its acceptability among potential end-users. Based on formative qualitative work and our own ongoing development of targeted long-acting products in nanosuspension formulations, we created eight hypothetical medication scenarios varying along six dichotomous attributes: administration location (home versus [vs.] clinic), dosing frequency (every 2 weeks vs. 1 week), injections per dose (one vs. two), injection pain (mild vs. moderate), injection site reaction (mild vs. moderate), and effectiveness (better vs. same as pills). PLWH from three outpatient care clinics in Seattle, WA and Riverside, CA rated acceptability (i.e., willingness to try each hypothetical medication) from 0 (very unlikely) to 100 (very likely). In conjoint analyses, we examined level and correlates of acceptability, the impact of each attribute on overall acceptability, and moderators of this effect. 

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