Efficacy and safety of long-acting cabotegravir compared with daily oral tenofovir disoproxil fumarate plus emtricitabine to prevent HIV infection in cisgender men and transgender women who have sex with men 1 year after study unblinding: a secondary analysis of the phase 2b and 3 HPTN 083 randomised controlled trial

Landovitz, Raphael J; Hanscom, Brett S; Clement, Meredith E; Tran, Ha V; Kallas, Esper G; Magnus, Manya; Sued, Omar; Sanchez, Jorge; Scott, Hyman; Eron, Joe J; del Rio, Carlos; Fields, Sheldon D; Marzinke, Mark A; Eshleman, Susan H; Donnell, Deborah; Spinelli, Matthew A; Kofron, Ryan M; Berman, Richard; Piwowar-Manning, Estelle M; Richardson, Paul A; Sullivan, Philip A; Lucas, Jonathan P; Anderson, Peter L; Hendrix, Craig W; Adeyeye, Adeola; Rooney, James F; Rinehart, Alex R; Cohen, Myron S; McCauley, Marybeth; Grinsztejn, Beatriz

doi:10.1016/s2352-3018(23)00261-8

Cited by 17 publications

(3 citation statements)

References 15 publications

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“…Unfortunately, despite the reassuring finding by Marrazzo et al of high protection among those consistently taking at least 4 doses per week, less than 40% of participants achieved this benchmark and had dramatic declines in adherence by 96 weeks. The percentage of participants with sustained adherence was much lower than in previous studies in MSM, underscoring the challenge of daily oral F/TDF for cisgender women. Barriers to PrEP adherence may vary by local context, although low perception of HIV risk, stigma, and poor social support are among the common reasons across settings .…”

contrasting

confidence: 62%

Shifting the Narrative of Preexposure Prophylaxis Adherence Counseling for Cisgender Women

Sheth,

Momplaisir,

Dumond

2024

JAMA

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contrasting

confidence: 62%

Shifting the Narrative of Preexposure Prophylaxis Adherence Counseling for Cisgender Women

Sheth,

Momplaisir,

Dumond

2024

JAMA

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“…There is also an urgent need for more discrete HIV/AIDS treatment and prevention strategies, with several at-risk groups preferring long-acting formulations, including injections, to daily dosing with tablet(s). , In January 2021, ViiV Healthcare’s Cabenuva (rilpivirine, cabotegravir) became the first Food and Drug Administration (FDA)-approved intramuscular long-acting injectable for HIV treatment in adults . This was shortly followed by the licensing of long-acting Apretude (cabotegravir) suspension for HIV prevention in at-risk groups because of its superiority compared to daily oral PrEP in reducing HIV incidence in randomized clinical trials (HIV Prevention Trials Network [HPTN] 083 and HPTN 084) …”

Section: Introductionmentioning

confidence: 99%

“…42 This was shortly followed by the licensing of long-acting Apretude (cabotegravir) suspension for HIV prevention in at-risk groups because of its superiority compared to daily oral PrEP in reducing HIV incidence in randomized clinical trials (HIV Prevention Trials Network [HPTN] 083 and HPTN 084). 43 The development of long-acting formulations tends to focus on the use of: water-insoluble drugs as suspensions in which drug particles are suspended in an aqueous medium; 44 microspheres were drugs are encapsulated within biodegradable polymers; 45 oil-based injections whereby hydrophobic drugs are dissolved in an oily medium and precipitate upon injection; 46 or preformed implants composed of nonbiodegradable polymers. 47 there are several challenges to their wider use as long-acting drug delivery platforms.…”

Section: Introductionmentioning

confidence: 99%

In Situ Forming, Enzyme-Responsive Peptoid-Peptide Hydrogels: An Advanced Long-Acting Injectable Drug Delivery System

Coulter,

Pentlavalli,

et al. 2024

J. Am. Chem. Soc.

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Long-acting drug delivery systems are promising platforms to improve patient adherence to medication by delivering drugs over sustained periods and removing the need for patients to comply with oral regimens. This research paper provides a proofof-concept for the development of a new optimized in situ forming injectable depot based on a tetrabenzylamine-tetraglycine-D-lysine-O-phospho-D-tyrosine peptoid-D-peptide formulation ((NPhe) 4 GGGGk(AZT)y(p)-OH). The chemical versatility of the peptoid-peptide motif allows low-molecular-weight drugs to be precisely and covalently conjugated. After subcutaneous injection, a hydrogel depot forms from the solubilized peptoid-peptide-drug formulation in response to phosphatase enzymes present within the skin space. This system is able to deliver clinically relevant concentrations of a model drug, the antiretroviral zidovudine (AZT), for 35 days in Sprague−Dawley rats. Oscillatory rheology demonstrated that hydrogel formation began within ∼30 s, an important characteristic of in situ systems for reducing initial drug bursts. Gel formation continued for up to ∼90 min. Small-angle neutron scattering data reveal narrow-radius fibers (∼0.78−1.8 nm) that closely fit formation via a flexible cylinder elliptical model. The inclusion of non-native peptoid monomers and D-variant amino acids confers protease resistance, enabling enhanced biostability to be demonstrated in vitro. Drug release proceeds via hydrolysis of an ester linkage under physiological conditions, releasing the drug in an unmodified form and further reducing the initial drug burst. Subcutaneous administration of (NPhe) 4 GGGGk(AZT)y(p)-OH to Sprague−Dawley rats resulted in zidovudine blood plasma concentrations within the 90% maximal inhibitory concentration (IC 90 ) range (30−130 ng mL −1 ) for 35 days.

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Updated guidelines on HIV post‐exposure prophylaxis: continued efforts towards increased accessibility

Allan‐Blitz,

Mayer

2024

J Int AIDS Soc.

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IntroductionHIV transmission is ongoing in both high‐ and low‐resource settings. Post‐exposure prophylaxis (PEP) remains an important tool in preventing HIV; however, PEP is significantly underutilized. The multitude of barriers to PEP implementation include low patient and provider awareness and acceptability, limited access to treatment and prevention services, and high rates of stigma. The World Health Organization (WHO) recently released updated guidance on the delivery of HIV PEP. This commentary aims to highlight the salient changes, evaluate how such recommendations can overcome the existing barriers to PEP implementation and discuss strategies needed to put the updated guidance into practice.DiscussionThe 2024 WHO PEP guidelines continue a trend towards increasing access to PEP. Most notably, the WHO now provides strong recommendations that: (1) PEP be delivered in community settings (e.g. pharmacies, police stations and online platforms), and (2) PEP delivery and monitoring be done via task sharing involving non‐specialist health workers (e.g. pharmacists or community health workers). The guidelines also emphasize that the PEP encounter is an important educable moment whereby a transition to pre‐exposure prophylaxis among individuals at continued risk for HIV infection should be discussed. The decentralization of PEP delivery has the potential to overcome numerous barriers to PEP implementation, reduce time to initiation and support adherence with the 28‐day course. To translate the recommendations into delivery programmes, however, much more work is needed. Detailed templates can help overcome the heterogeneity of both the community settings in which PEP can now be provided and the populations (e.g. survivors of sexual assault, healthcare workers, sex workers, etc.) among whom PEP may be indicated. Training of the workforce will be essential, which should include, as emphasized by the WHO, training in trauma‐based care. Novel formulations of and delivery mechanisms for PEP are also emerging, and how such iterations can synergize with decentralized PEP delivery programmes remains to be seen.ConclusionsThe updated WHO PEP guidelines make major strides towards increasing access to PEP. Realization of such aims will require ongoing evaluation and support given the heterogeneity in who benefits most from PEP.

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Cited by 17 publications

References 15 publications

Shifting the Narrative of Preexposure Prophylaxis Adherence Counseling for Cisgender Women

Shifting the Narrative of Preexposure Prophylaxis Adherence Counseling for Cisgender Women

In Situ Forming, Enzyme-Responsive Peptoid-Peptide Hydrogels: An Advanced Long-Acting Injectable Drug Delivery System

Updated guidelines on HIV post‐exposure prophylaxis: continued efforts towards increased accessibility

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