Examining the Safety, Pharmacokinetics, and Pharmacodynamics of a Rectally Administered IQP-0528 Gel for HIV Pre-Exposure Prophylaxis: A First-In-Human Study

Al-khouja, Amer; Shieh, Eugenie; Fuchs, Edward J.; Marzinke, Mark A.; Bakshi, Rahul P.; Hummert, Pamela; Ham, Anthony S.; Buckheit, Karen W.; Breakey, Jennifer C.; Weld, Ethel D.; Chen, Huan; Caffo, Brian; Buckheit, Robert W.; Hendrix, Craig W.

doi:10.1089/aid.2020.0188

Cited by 7 publications

(5 citation statements)

References 35 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…We observed mean cumulative p24 differences after PrEP exposure of −144 and −179 pg/ml/mg in the 2 h – double dose and 7 days – single-dose groups, respectively. Our ex-vivo model yield results of cumulative p24 levels before PrEP comparable to those reported in other ex-vivo studies with rectal explants at baseline [25,29,30].…”

Section: Discussionsupporting

confidence: 80%

Ex-vivo rectal tissue infection with HIV-1 to assess time to protection following oral preexposure prophylaxis with tenofovir disoproxil/emtricitabine

Chawki,

Goldwirt,

Mouhebb

et al. 2023

Aids

View full text Add to dashboard Cite

Objectives: We wished to assess time to protection from HIV-1 infection following oral tenofovir disoproxil and emtricitabine (TDF/FTC) as pre-exposure prophylaxis (PrEP), using ex vivo rectal tissue infections and drug concentration measures in blood and rectal tissue. Design/Methods: Participants from the ANRS PREVENIR study (NCT03113123) were offered this sub-study after a 14-day wash-out. We used an ex vivo model to evaluate rectal tissue HIV-1 susceptibility before and after PrEP, two hours after 2 pills or seven days of a daily pill of TDF/FTC. PrEP efficacy was expressed by the difference (after-before) of 14-day cumulative p24 antigen levels. TFV-DP and FTC-TP levels were measured in rectal tissue and PBMCs and correlated with HIV-1 infection. Results: Twelve and eleven males were analysed in the 2 hours–double dose and 7 days–single dose groups, respectively. Cumulative p24 differences after-before PrEP were -144pg/ml/mg (IQR[-259;-108]) for the 2 hours–double dose group (p = 0.0005) and -179pg/ml/mg (IQR[-253;-86]) for the 7 days–single dose group (p = 0.001), with no differences between groups (p = 0.93). Rectal TFV-DP was below quantification after a double dose, but FTC-TP levels were similar to levels at seven days. There was a significant correlation between rectal FTC-TP levels and p24 changes after a double dose (R = -0.84; p = 0.0001). Conclusions: Oral TDF/FTC provided similar protection against HIV-1 infection of rectal tissue 2 hours after a double dose or 7 days of a daily dose. At 2 hours, this protection seems driven by high FTC-TP concentrations in rectal tissue. This confirms the importance of combining TDF and FTC to achieve early protection.

show abstract

Section: Discussionsupporting

confidence: 80%

Ex-vivo rectal tissue infection with HIV-1 to assess time to protection following oral preexposure prophylaxis with tenofovir disoproxil/emtricitabine

Chawki,

Goldwirt,

Mouhebb

et al. 2023

Aids

View full text Add to dashboard Cite

show abstract

“…In a phase one study, seven HIV-negative individuals received one 10 mL rectal dose of 1% IQP-0528 gel, and no drug-associated adverse event was observed (NCT03082690). However, the application of IQP-0528 is limited because of its rapid clearance and its inability to penetrate vaginal tissues following the rectal dosing 149 .…”

Section: Development Of Novel Nrtis and Nnrtismentioning

confidence: 99%

Approved HIV reverse transcriptase inhibitors in the past decade

Wang

Clercq

2022

Acta Pharmaceutica Sinica B

View full text Add to dashboard Cite

“…The gel is a suspension of inorganic or organic particles interpenetrated by an aqueous or nonaqueous liquid (Antimisiaris & Mourtas, 2015; Garg et al, 2010; Rohan et al, 2014). Its high lubrication capacity and wide acceptance contribute to it being the most widely studied formulation as vaginal microbicide (Al‐Khouja et al, 2020; Bunge et al, 2018; Delany‐Moretlwe et al, 2018; Halwes et al, 2016). The tablets are polymers that gel in the presence of vaginal fluids and overcome stability concerns related to gels (Antimisiaris & Mourtas, 2015; Garg et al, 2010; Rohan et al, 2014).…”

Section: Vaginal Formulations: Development and Characterizationmentioning

confidence: 99%

“…Several antiretroviral drugs are currently in advanced stages of development as microbicides, either vaginally or rectally (Al‐Khouja et al, 2020; Bunge et al, 2020; A. Y. Liu et al, 2019; MTN, 2020; Pleasants et al, 2020). However, there is no commercially available microbicide due to the lack of effectiveness of these products in preclinical and clinical trials for many reasons (Baeten et al, 2020; Musekiwa et al, 2020; Notario‐Perez et al, 2017).…”

Section: The Importance Of Vaginal Microbicides To Prevent Hiv‐1mentioning

confidence: 99%

Baseline and time‐updated factors in preclinical development of anionic dendrimers as successful anti‐HIV‐1 vaginal microbicides

Rodriguez-Izquierdo

Sepúlveda‐Crespo

Lasso³

et al. 2022

WIREs Nanomed Nanobiotechnol

View full text Add to dashboard Cite

Although a wide variety of topical microbicides provide promising in vitro and in vivo efficacy, most of them failed to prevent sexual transmission of human immunodeficiency virus type 1 (HIV-1) in human clinical trials. In vitro, ex vivo, and in vivo models must be optimized, considering the knowledge acquired from unsuccessful and successful clinical trials to improve the current gaps and the preclinical development protocols. To date, dendrimers are the only nanotool that has advanced to human clinical trials as topical microbicides to prevent HIV-1 transmission. This fact demonstrates the importance and the potential of these molecules as microbicides. Polyanionic dendrimers

show abstract

Examining the Safety, Pharmacokinetics, and Pharmacodynamics of a Rectally Administered IQP-0528 Gel for HIV Pre-Exposure Prophylaxis: A First-In-Human Study

Cited by 7 publications

References 35 publications

Ex-vivo rectal tissue infection with HIV-1 to assess time to protection following oral preexposure prophylaxis with tenofovir disoproxil/emtricitabine

Ex-vivo rectal tissue infection with HIV-1 to assess time to protection following oral preexposure prophylaxis with tenofovir disoproxil/emtricitabine

Approved HIV reverse transcriptase inhibitors in the past decade

Baseline and time‐updated factors in preclinical development of anionic dendrimers as successful anti‐HIV‐1 vaginal microbicides

Contact Info

Product

Resources

About