Novel Bilayer Microarray Patch‐Assisted Long‐Acting Micro‐Depot Cabotegravir Intradermal Delivery for HIV Pre‐Exposure Prophylaxis

Abstract Background 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 human immunodeficiency virus (HIV) PrEP being tested in phase III trials. Methods We use a mathematical model of the HIV epidemic in South Africa to simulate CAB LA uptake by population groups with different levels of HIV risk. We compare the trajectory of the HIV epidemic until 2050 with and without CAB LA to estimate the impact of the intervention. Results Delivering CAB LA to 10% of the adult population could avert more than 15% of new infections from 2023 to 2050. The impact would be lower but more efficient if delivered to populations at higher HIV risk: 127 person-years of CAB LA use would be required to avert one HIV infection within 5 years if used by all adults and 47 person-years if used only by the highest risk women. Conclusions If efficacious, a CAB LA intervention could have a substantial impact on the course of the HIV epidemic in South Africa. Uptake by those at the highest risk of infection, particularly young women, could improve the efficiency of any intervention.

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Corrigendum to “Nanoencapsulation introduces long-acting phenomenon to tenofovir alafenamide and emtricitabine drug combination: A comparative pre-exposure prophylaxis efficacy study against HIV-1 vaginal transmission” [Journal of Controlled Release 294 (2019) 216–225]

Journal of Controlled Release ◽

10.1016/j.jconrel.2019.05.002 ◽

2019 ◽

Vol 304 ◽

pp. 101

Author(s):

Subhra Mandal ◽

Guobin Kang ◽

Pavan Kumar Prathipati ◽

You Zhou ◽

Wenjin Fan ◽

...

Keyword(s):

Controlled Release ◽

Drug Combination ◽

Efficacy Study ◽

Vaginal Transmission ◽

Tenofovir Alafenamide ◽

Long Acting ◽

Exposure Prophylaxis ◽

Hiv 1

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Prepared for PrEP: preferences for HIV pre-exposure prophylaxis among Chinese men who have sex with men in an online national survey

BMC Infectious Diseases ◽

10.1186/s12879-019-4692-x ◽

2019 ◽

Vol 19 (1) ◽

Cited By ~ 1

Author(s):

Wenting Huang ◽

Dan Wu ◽

Jason J. Ong ◽

M. Kumi Smith ◽

Fan Yang ◽

...

Keyword(s):

National Survey ◽

Secondary Analysis ◽

Chinese Men ◽

Sex With Men ◽

Partner Types ◽

Long Acting ◽

Negotiated Safety ◽

Exposure Prophylaxis ◽

Larger Sample ◽

Oral Prep

Abstract Background Pre-exposure prophylaxis (PrEP) is not widely available in China. Previous studies reported low awareness and inconclusive findings on the acceptability of PrEP among Chinese men who have sex with men (MSM). Methods We conducted a secondary analysis of an online national survey comparing preferences for oral and long-acting injectable PrEP among MSM and identifying correlates of preferences. The study did not collect detailed information about partner types that may influence negotiated safety and PrEP uptake. Results Nine-hundred and seventy-nine men from the larger sample of 1045 men responded to the PrEP survey questions. Most men (81.9%) had never heard of PrEP, but reported interest in using PrEP. More participants chose injectable PrEP (36.3%) as their preferred formulation than oral PrEP (24.6%). Men who had at least two HIV tests (adjusted OR = 1.36, 95%CI 1.04, 1.78) more commonly preferred injectable PrEP. Conclusion Our findings may help inform PrEP messaging in areas where PrEP has yet to be scaled up.

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Antiretroviral pre-exposure prophylaxis preferences among men who have sex with men in Vietnam: results from a nationwide cross-sectional survey

Sexual Health ◽

10.1071/sh15144 ◽

2016 ◽

Vol 13 (5) ◽

pp. 465 ◽

Cited By ~ 6

Author(s):

Catherine E. Oldenburg ◽

Bao Le ◽

Hoang Thi Huyen ◽

Dinh Duc Thien ◽

Nguyen Hoang Quan ◽

...

Keyword(s):

Online Survey ◽

Cross Sectional Survey ◽

Cross Sectional ◽

Rectal Microbicides ◽

Logistic Regression Models ◽

Aids Epidemic ◽

Sex With Men ◽

Long Acting ◽

Rectal Microbicide ◽

Exposure Prophylaxis

Background The HIV/AIDS epidemic in Vietnam is concentrated in subgroups of the population, including men who have sex with men (MSM). Pre-exposure prophylaxis (PrEP) is a viable strategy for HIV prevention, but knowledge about and preferences for PrEP delivery among Vietnamese MSM are not well understood. Methods: In 2015, an online survey was conducted with recruitment via social networking websites for MSM and peer recruitment. A description of daily oral, long-acting injectable, and rectal microbicide formulations of PrEP was provided to participants. Participants were asked about their prior awareness of and interest in PrEP, and ranked their most preferred PrEP modality. Multivariable logistic regression models were used to assess factors associated with having heard of PrEP and preference for each PrEP modality. Results: Of 548 participants who answered demographic and PrEP-related questions, 26.8% had previously heard of PrEP and most (65.7%) endorsed rectal microbicides as their most preferred PrEP delivery modality. Commonly-cited perceived barriers to uptake of PrEP included concern about side-effects, perception about being HIV positive, and family or friends finding out about their sexual behaviour. In multivariable models, older participants less often endorsed rectal microbicides (adjusted odds ratio (AOR) 0.95 per year, 95% confidence interval (CI) 0.91–0.99) and more often endorsed long-acting injectables (AOR 1.08 per year, 95% CI 1.03 to 1.14) as their preferred PrEP modality. Participants who were willing to pay more for PrEP less often endorsed rectal microbicides (AOR 0.81, 95% CI 0.72–0.92) and more often endorsed long-acting injectables (AOR 1.17, 95% CI 1.01–1.35) and daily oral pills (AOR 1.16, 95% CI 1.00–1.35) as their preferred form of PrEP. Conclusions: A variety of PrEP modalities were acceptable to MSM in Vietnam, but low knowledge of PrEP may be a barrier to implementation.

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LB8. Microarray Patch Delivery of Long-Acting HIV PrEP and Contraception

Open Forum Infectious Diseases ◽

10.1093/ofid/ofz415.2491 ◽

2019 ◽

Vol 6 (Supplement_2) ◽

pp. S996-S996 ◽

Cited By ~ 1

Author(s):

Annie Rein-Weston ◽

Ismaiel Tekko ◽

Lalit Vora ◽

Courtney Jarrahian ◽

Bill Spreen ◽

...

Keyword(s):

Drug Loading ◽

Accelerated Aging ◽

Hormonal Contraceptive ◽

Self Administration ◽

Map Projections ◽

User Acceptability ◽

Microneedle Patch ◽

Long Acting ◽

Exposure Prophylaxis

Abstract Background The purpose of this research was to develop a microarray patch (MAP; also known as a microneedle patch) for delivery of long-acting cabotegravir (CAB LA) for HIV pre-exposure prophylaxis (PrEP) and co-delivery of long-acting CAB LA and a hormonal contraceptive to enable a future multi-purpose prevention technology. This abstract presents preclinical pharmacokinetic results of MAP delivery of CAB LA. Methods MAPs are an alternative delivery technology in clinical development for intradermal delivery of vaccines and pharmaceuticals. A MAP consists of an array of micron-scale projections (<1 mm in height) amassed on a baseplate and applied to the skin like a bandage. MAPs could provide a discreet delivery system that enables self-administration, which could be particularly important for HIV prevention and contraception for young women and girls in low-resource settings. The purpose of this 3-year, USAID-funded project is to develop a MAP for delivery of long-acting HIV PrEP through to the point of Phase I clinical readiness. Key attributes of the MAP for long-acting HIV PrEP, as defined by our target product profile, include patch size similar to commercially available transdermal patches (20 to 140 cm2), wear-time of less than 24 hours (ideally 20 minutes), weekly or monthly administration to achieve therapeutic efficacy, and ideally successful self-administration after reading simple product instructions. Results We successfully formulated and optimized MAP projection geometry to accommodate high drug-loading requirements of CAB LA (5.86 mg CAB LA per 1 cm2 MAP), a hydrophobic drug. The MAPs are stable for 6 months under accelerated aging conditions in foil packaging, readily pierce the skin, and rapidly dissolve. In rats, plasma concentration levels of CAB LA were maintained above therapeutic targets of 4xPA-IC90 for 28 days; however, bioavailability was lower than IM or ID injection controls. Photos: QUB. MAPs dissolving over time in phosphate-buffered solution; MAP projections fully dissolved within 25 minutes. Conclusion Additional development work is warranted, including optimizing bioavailability, evaluating MAPs as a maintenance dose in vivo, conducting cost of manufacturing and cost of delivery analyses, and assessing potential end-user acceptability. Disclosures Bill Spreen, PharmD, ViiV Healthcare (Employee), Trevor Scott, RPh, PhD, ViiV Healthcare (Employee). Others Authors: No reported disclosures.

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Suboptimal uptake, retention, and adherence of daily oral PrEP among people with OUD receiving HCV treatment

Open Forum Infectious Diseases ◽

10.1093/ofid/ofab658 ◽

2021 ◽

Author(s):

C Brokus ◽

S Kattakuzhy ◽

B Gayle ◽

S Narayanan ◽

A Davis ◽

...

Keyword(s):

Opioid Use Disorder ◽

Self Report ◽

Washington Dc ◽

Opioid Use ◽

Hcv Treatment ◽

Community Based ◽

Treatment Medication ◽

Long Acting ◽

Exposure Prophylaxis ◽

Hiv Negative

Abstract Introduction Daily oral pre-exposure prophylaxis (PrEP) with tenofovir/emtricitabine (TDF/FTC) prevents HIV among people who inject drugs (PWID). Despite rising HIV incidence and injection drug use, PrEP use remains low and there is limited research about uptake, adherence, and retention among PWID. Methods The ANCHOR investigation evaluated a community-based care model collocating hepatitis C (HCV) treatment, medication for opioid use disorder (OUD), and PrEP in individuals in Washington, DC-Baltimore. PrEP counseling was conducted from HCV treatment Day 0 until Week 24. Subjects could start any time during this window, were followed for 48 weeks, and were assessed for adherence by self-report and dried bloodspot TDF analysis. Results 198 participants were enrolled, of whom 185 (93%) were HIV-negative. Twenty-nine individuals (15.7% of HIV-negative cohort) initiated PrEP. 116 participants (62.7%) met 2014 CDC PrEP criteria due to IDU (82, 44.3%), sex (9, 4.9%), or both practices (25, 13.5%). Providers recommended PrEP to 94 individuals (50.8%), and recommendation was associated with PrEP uptake. Median treatment duration was 104 days (IQR 28, 276), with 8 participants retained through Week 48. Adherence was variable over time by self-report and declined by TDF analysis. No HIV seroconversions occurred. Conclusions This cohort of people with HCV and OUD experienced low uptake of PrEP despite the majority meeting CDC criteria. High rates of disruption and discontinuation, compounded by variable adherence, made TDF/FTC a suboptimal prevention strategy. Emerging modalities like long-acting formulations may address these barriers, but PWID have been excluded from their development to date.

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Multispecies Evaluation of a Long-Acting Tenofovir Alafenamide Subdermal Implant for HIV Prophylaxis

Frontiers in Pharmacology ◽

10.3389/fphar.2020.569373 ◽

2020 ◽

Vol 11 ◽

Author(s):

Manjula Gunawardana ◽

Mariana Remedios-Chan ◽

Debbie Sanchez ◽

Simon Webster ◽

Patricia Galvan ◽

...

Keyword(s):

Animal Models ◽

Active Agent ◽

The Body ◽

Dermal Tissue ◽

Metabolite Concentrations ◽

Tenofovir Alafenamide ◽

Long Acting ◽

Exposure Prophylaxis ◽

Hiv 1 ◽

Subdermal Implant

New HIV-1 infection rates far outpace the targets set by global health organizations, despite important progress in curbing the progression of the epidemic. Long-acting (LA) formulations delivering antiretroviral (ARV) agents for HIV-1 pre-exposure prophylaxis (PrEP) hold significant promise, potentially facilitating adherence due to reduced dosing frequency compared to oral regimens. We have developed a subdermal implant delivering the potent ARV drug tenofovir alafenamide that could provide protection from HIV-1 infection for 6 months, or longer. Implants from the same lot were investigated in mice and sheep for local safety and pharmacokinetics (PKs). Ours is the first report using these animal models to evaluate subdermal implants for HIV-1 PrEP. The devices appeared safe, and the plasma PKs as well as the drug and metabolite concentrations in dermal tissue adjacent to the implants were studied and contrasted in two models spanning the extremes of the body weight spectrum. Drug and drug metabolite concentrations in dermal tissue are key in assessing local exposure and any toxicity related to the active agent. Based on our analysis, both animal models were shown to hold significant promise in LA product development.

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