Recent Publications

Be informed about the latest research and clinical studies being done in long-acting, extended release drugs for HIV and TB.

Predicting pharmacokinetics of a tenofovir alafenamide subcutaneous implant using PBPK modelling

Date Posted: 
Mon, 05/18/2020
Author(s): 
Rajoli RKR, Demkovich ZR, Flexner C, Owen A, Siccardi M.
Citation(s): 
Antimicrob Agents Chemother. 2020 May 18:AAC.00155-20. doi: 10.1128/AAC.00155-20.


Long-acting (LA) administration using a subcutaneous (SC) implant presents opportunities to simplify administration of antiretroviral drugs, improve pharmacological (PK) profile and overcome sub-optimal adherence associated with daily oral formulations. Tenofovir alafenamide (TAF) is a highly potent nucleoside reverse transcriptase inhibitor (NRTI) and an attractive agent for LA delivery, with a high potency and long intracellular half-life. The aim of this study was to predict minimum TAF doses required to achieve concentrations effective for HIV pre-exposure prophylaxis (PrEP). Daily drug-release requirements were then ascertained by averaging across the dosing interval.

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

Date Posted: 
Fri, 06/05/2020
Author(s): 
Yee KL, Mittal S, Fan L, et al
Citation(s): 
J Clin Pharm Ther. 2020 Jun 5. doi: 10.1111/jcpt.13182. [Epub ahead of print] PMID: 32501541 [PubMed - as supplied by publisher]


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 Posted: 
Wed, 06/03/2020
Author(s): 
Smith JA, Garnett GP, Hallett TB.
Citation(s): 
J Infect Dis. 2020 Jun 3. pii: jiaa296. doi: 10.1093/infdis/jiaa296. [Epub ahead of print] PMID: 32492704 [PubMed - as supplied by publisher]


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.

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 Posted: 
Mon, 05/18/2020
Author(s): 
HIV Prevention Trials Network
Citation(s): 
Press Release

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 multi-site study of women living with HIV's perceived barriers to, and interest in, long-acting injectable anti-retroviral therapy.

Date Posted: 
Mon, 03/02/2020
Author(s): 
Philbin MM, Parish C, Kinnard EN., et al.
Citation(s): 
Philbin MM, Parish C, Kinnard EN, Reed SE, Kerrigan D, Alcaide M, Cohen MH, Sosanya O, Sheth AN, Adimora AA, Cocohoba J, Goparaju L, Golub ET, Fischl M, Metsch LR. A multi-site study of women living with HIV's perceived barriers to, and interest in,

Adherence to antiretroviral therapy (ART) is imperative for viral suppression and reducing HIV transmission, but many people living with HIV report difficultly sustaining long-term adherence. Long-acting injectable (LAI) ART has the potential to transform HIV treatment and prevention. However, little LAI ART-related behavioral research has occurred among women, particularly outside of clinical trials.

Long-acting rilpivirine (RPV LA) pre-exposure prophylaxis does not inhibit vaginal transmission of RPV-resistant HIV-1 nor select for high frequency drug resistance in humanized mice.

Date Posted: 
Wed, 01/22/2020
Author(s): 
Melody K, Roy CN, Kline C,, et al.
Citation(s): 
Melody K, Roy CN, Kline C, Cottrell ML, Evans D, Shutt K, Pennings PS, Keele BF, Bility M, Kashuba ADM, Ambrose Z. Long-acting rilpivirine (RPV LA) pre-exposure prophylaxis does not inhibit vaginal transmission of RPV-resistant HIV-1 nor select for high


As a long-acting formulation of the non-nucleoside reverse transcriptase inhibitor rilpivirine (RPV LA) has been proposed for use as pre-exposure prophylaxis (PrEP) and the prevalence of transmitted RPV-resistant viruses can be relatively high, we evaluated the efficacy of RPV LA to inhibit vaginal transmission of RPV-resistant HIV-1 in humanized mice. 

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

Date Posted: 
Fri, 12/20/2019
Author(s): 
Bollinger RC, Thio CL, Sulkowski MS, et al.
Citation(s): 
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. 2019 Dec 20. pii: S2352-3018(19)30


The first long-acting formulations of HIV drugs are undergoing regulatory review for use in maintenance of viral suppression in people with HIV.

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

Date Posted: 
Fri, 12/20/2019
Author(s): 
Bollinger RC, Thio CL, Sulkowski MS, et al.
Citation(s): 
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. 2019 Dec 20. pii: S2352-3018(19)30

The first long-acting formulations of HIV drugs are undergoing regulatory review for use in maintenance of viral suppression in people with HIV.

Long-acting implants to treat and prevent HIV infection

Date Posted: 
Fri, 12/06/2019
Author(s): 
Weld ED, Flexner C.
Citation(s): 
Curr Opin HIV AIDS. 2020 Jan;15(1):33-41. doi: 10.1097/COH.0000000000000591.


Subcutaneous implants are a promising technology to enable long-acting parenteral delivery of antiretroviral drugs (ARV) because they may be able to provide protective drugs concentrations for a year or longer following a single implant. The present review covers the current status of preclinical and clinical development of antiretroviral implants.

Modelling the intradermal delivery of microneedle array patches for long-acting antiretrovirals using PBPK

Date Posted: 
Fri, 12/06/2019
Author(s): 
Rajoli RKR, Flexner C, Chiong J, Owen A, et al.
Citation(s): 
Eur J Pharm Biopharm. 2019 Nov;144:101-109. doi: 10.1016/j.ejpb.2019.09.011. Epub 2019 Sep 13.

Existing HIV therapy using oral antiretrovirals (ARVs) can result in pill fatigue and sub-optimal adherence. Microneedle array patches (MAPs) offer non-invasive, blood-free and painless drug delivery, and may improve patient adherence.

Pages