Acceptability of tenofovir gel as a vaginal microbicide among women in a phase I trial a mixed-methods study,

2020 ◽  
Author(s):  
Lungwani Muungo
Keyword(s):  
Clinical Trials ◽  
Phase I ◽  
Phase I Trial ◽  
Hiv Transmission ◽  
Sexual Transmission ◽  
Initial Product ◽  
Vaginal Microbicides ◽  
Tenofovir Gel ◽  
Gender Based ◽  
Sexual Transmission Of Hiv

THE GLOBAL HIV EPIDEMIC increasingly affectswomen.1 For most, the only risk factor for becominginfected is the behavior of their male sexualpartners.1 Condoms often are unacceptableand insufficiently used,2–4 gender-based powerimbalances can make them difficult to negotiate,4–7 and religious beliefs, fertility needs, fear ofimplied infidelity, and preferences for sex withouta barrier are challenges to their acceptabilityand use. Women-initiated HIV prevention methodsare urgently needed, making the developmentof vaginal microbicides that reduce the likelihoodof sexual transmission of HIV a majorpublic health priority.First-generation vaginal microbicides will mostlikely be topical gels inserted into the vagina withan applicator. A variety of microbicides is currentlyunder development, and six have enteredlate-stage clinical trials.8–12 Initial product acceptabilityhas been assessed in clinical trials,13–16 surveysof product attributes among potentialusers17,18 and their partners,19 and studies that useover-the-counter (OTC) surrogates or placebo gelwith presumed similar formulation and applicationcharacteristics as eventual products.20–23 Acceptabilityassessments in early clinical trials areespecially important because their findings can influencefurther development of the product.Here, we report on acceptability data amongwomen participating in a phase I trial of tenofovirgel, a candidate microbicide that inhibits HIV reversetranscriptase. Details of the trial are reportedelsewhere,24 as is acceptability amongmale partners of trial participants.25 This was thefirst human trial of a topical antiretroviral thatspecifically inhibits a necessary replication stepin the HIV life cycle. Interest in this approach toHIV prevention has increased in recent yearssince efficacy trials of a topical surfactant(nonoxynyl-9) and a nonspecific inhibitor of HIVbinding (cellulose sulfate) indicated that thesetwo types of compounds were not protective andpotentially increased HIV transmission in womenwho had frequent sexual exposures to HIV. Severallarger-scale, expanded safety and proof-ofconcepttrials of tenofovir gel are now underway,based in part on the safety, tolerability, and acceptabilityof this microbicide demonstrated inthe study described in this paper.

scholarly journals Provider Recommendations for Phase I Clinical Trials Within a Shared Decision-Making Model in Phase I Cancer Clinical Trial Discussions

2020 ◽  
Vol 16 (9) ◽  
pp. e859-e867
Author(s):  
Rachel S. Hianik ◽  
Gavin P. Campbell ◽  
Eli Abernethy ◽  
Colleen Lewis ◽  
Christina S. Wu ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Decision Making ◽  
Clinical Trials ◽  
Phase I ◽  
Shared Decision Making ◽  
Phase I Trial ◽  
Performance Status ◽  
Shared Decision ◽  
Phase I Clinical Trials ◽  
Decision Making Model

PURPOSE: Debate continues over whether explicit recommendations for a clinical trial should be included as an element of shared decision making within oncology. We aimed to determine if and how providers make explicit recommendations in the setting of phase I cancer clinical trials. METHODS: Twenty-three patient/provider conversations about phase I trials were analyzed to determine how recommendations are made and how the conversations align with a shared decision-making framework. In addition, 19 providers (9 of whose patient encounters were observed) were interviewed about the factors they consider when deciding whether to recommend a phase I trial. RESULTS: We found that providers are comprehensive in the factors they consider when recommending clinical trials. The two most frequently stated factors were performance status (89%) and patient preferences (84%). Providers made explicit recommendations in 19 conversations (83%), with 12 of those being for a phase I trial (12 [63%] of 19). They made these recommendations in a manner consistent with a shared decision-making model; 18 (95%) of the 19 conversations during which a recommendation was made included all steps, or all but 1 step, of shared decision making, as did 11 of the 12 conversations during which a phase I trial was recommended. In 7 (58%) of these later conversations, providers also emphasized the importance of the patient’s opinion. CONCLUSION: We suggest that providers not hesitate to make explicit recommendations for phase I clinical trials, because they are able to do so in a manner consistent with shared decision making. With further research, these results can be applied to other clinical trial settings.

scholarly journals Chitosan-Based Mucoadhesive Vaginal Tablets for Controlled Release of the Anti-HIV Drug Tenofovir

Pharmaceutics ◽  
2019 ◽  
Vol 11 (1) ◽  
pp. 20 ◽  
Author(s):  
Raúl Cazorla-Luna ◽  
Fernando Notario-Pérez ◽  
Araceli Martín-Illana ◽  
Roberto Ruiz-Caro ◽  
Aitana Tamayo ◽  
...  
Keyword(s):  
Sexual Transmission ◽  
Microstructural Characterization ◽  
Vaginal Fluid ◽  
Vaginal Mucosa ◽  
Vaginal Microbicides ◽  
Polyelectrolyte Complexes ◽  
Antiretroviral Drug ◽  
Sexual Transmission Of Hiv ◽  
Self Protection

Vaginal microbicides have the potential to give women at high risk of contracting HIV the option of self-protection by preventing the sexual transmission of the virus. In this paper, mucoadhesive vaginal tablets based on chitosan, alone and in combination with pectin and locust bean gum, were developed for the sustained release of tenofovir (an antiretroviral drug). The formulations were placed in simulant vaginal fluid (SVF) to swell, and Hg porosity and SEM microscopy were used for the microstructural characterization of the swelling witnesses. The results show that the association of pectin and chitosan generated polyelectrolyte complexes and produced a robust system able to maintain its structure during the swelling process, when small pores are formed. Drug release and bovine vaginal mucoadhesion studies were performed in SVF showing that tenofovir-controlled dissolution profiles and adhesion to the mucosa were conditioned by the swelling processes of the polymer/s in each formulation. Tablets based on chitosan/pectin have the most homogeneous tenofovir dissolution profiles and last up to 96 h, remaining attached to the vaginal mucosa for the same period. These formulations can therefore be considered a good option for the self-protection of women from the sexual transmission of HIV.

scholarly journals Strategies to prevent HIV transmission to serodiscordant couples

2015 ◽  
Vol 18 (suppl 1) ◽  
pp. 169-182 ◽  
Author(s):  
Ronaldo Campos Hallal ◽  
Juan Carlos Raxach ◽  
Nêmora Tregnago Barcellos ◽  
Ivia Maksud
Keyword(s):  
Hiv Transmission ◽  
Sexual Transmission ◽  
Sexual Practices ◽  
Transmission Risk ◽  
Prevention Policy ◽  
Serodiscordant Couples ◽  
Prevention Interventions ◽  
Single Strategy ◽  
Sexual Transmission Of Hiv ◽  
Exposure Prophylaxis

ABSTRACTIntroduction:The use antiretroviral reduces the sexual transmission of HIV, expanding interventions for serodiscordant couples.Objective:This article aims to review the use of antiretroviral and other prevention interventions among serodiscordant couples and to analyze its use in Brazil.Methods:A retrospective review was performed through the MEDLINE database and bases included in the Biblioteca Virtual em Saúde.Results:The articles recovered exhibit four main strategies: (1) condom; (2) reduction of risks in sexual practices; (3) use of antiretrovirals, particularly early initiation of antiretroviral therapy (TASP) and pre-exposure prophylaxis (PrEP); (4) risk reduction in reproduction.Discussion:TASP is highly effective in reducing sexual transmission, PrEP was tested in serodiscordant couples and both reduce the sexual transmission risk in different sexual practices, enabling individualized prevention strategies.Conclusions:When used in combination, antiretrovirals and sexual practices with condoms offer greater efficacy than any single strategy. The combined use of new and old strategies allows us to build a prevention policy for all.

Characteristics and outcomes of patients with gallbladder cancer and cholangiocarcinoma referred to a phase I clinic.

2012 ◽  
Vol 30 (4_suppl) ◽  
pp. 364-364 ◽  
Author(s):  
Ishwaria Mohan Subbiah ◽  
Vivek Subbiah ◽  
Ahmed Omar Kaseb ◽  
Filip Janku ◽  
Jennifer J. Wheler ◽  
...  
Keyword(s):  
Overall Survival ◽  
Clinical Trials ◽  
Phase I ◽  
Median Time ◽  
Median Survival ◽  
Phase I Trial ◽  
Mutational Analysis ◽  
Phase 1 ◽  
Cancer Center ◽  
Phase I Clinical Trials

364 Background: The prognosis of cholangiocarcinoma (CC) and gallbladder carcinoma (GC) remains grim. The purpose of this study was to report the presenting characteristics and outcomes of patients with CC and GC treated on phase 1 clinical trials focused on targeted agents at a major cancer center. Methods: We reviewed the records of consecutive patients with GC and CC in the Phase I Clinical Trials Program at the M. D. Anderson Cancer Center from Nov 2004. We assessed the relationship between overall survival, patients' tumor types, and mutations, demographic and clinical characteristics. Results: Fifty-two patients were identified (7 with GC, 45 with CC). The median age was 58 yrs (range, 20-75 yrs). ECOG performance status (PS) was 0, 1, 2, and 3 in 9 (17%), 30 (58%), 7 (13%), and 6 (12%) pts, respectively. Median number of prior therapies was 3 (range 0-17). The median time from diagnosis of metastatic disease to primary Phase I clinic evaluation was 14.6 months. Of 52 patients, 17 (33%) were not enrolled on a Phase I trial due to decline in PS (n=13) or decision to pursue other treatments (n=4). Of 35 patients evaluable for response, 2 (6%) had a partial response (PR), and 3 (9%) had stable disease > 4 months. Prognostic factors analyzed include Hg < 10.5 g/dL, elevated CA 19-9 (>47 ng/mL), ECOG PS > 3, LDH > 618 IU/L, albumin < 3.5 g/dL, platelets < 150 K/UL, and number of metastatic sites. Full analysis including the mutational analysis for PIK3CA, KRAS, BRAF, TP53 is in progress. Median survival since presentation to the Phase I clinic was 4.1 months (range 2.3 - 30.8 months). Median overall survival from diagnosis was 23.9 months. The median survival since enrollment in a Phase I trial was 4.6 months w the median time to disease progression on Phase I treatment was 2.2 months (range 0.6 - 25.6 months). Conclusions: Prognosis of pts with CC and GC referred for phase I studies remains poor. Further analysis including complete mutational profiles of CC and GC patients will be reported.

scholarly journals Factors Important to the Prioritization and Development of Successful Topical Microbicides for HIV-1

2012 ◽  
Vol 2012 ◽  
pp. 1-12 ◽  
Author(s):  
Karen W. Buckheit ◽  
Robert W. Buckheit
Keyword(s):  
Clinical Trials ◽  
Ex Vivo ◽  
Sexual Transmission ◽  
Virus Transmission ◽  
Preclinical Development ◽  
Sexual Transmission Of Hiv ◽  
The Right ◽  
Hiv 1

Significant advancements in topical microbicide development have occurred since the prevention strategy was first described as a means to inhibit the sexual transmission of HIV-1. The lack of clinical efficacy of the first generation microbicide products has focused development attention on specific antiretroviral agents, and these agents have proven partially successful in human clinical trials. With greater understanding of vaginal and rectal virus infection, replication, and dissemination, better microbicide products and delivery strategies should result in products with enhanced potency. However, a variety of development gaps exist which relate to product dosing, formulation and delivery, and pharmacokinetics and pharmacodynamics which must be better understood in order to prioritize microbicide products for clinical development. In vitro, ex vivo, and in vivo models must be optimized with regard to these development gaps in order to put the right product at the right place, at the right time, and at the right concentration for effective inhibition of virus transmission. As the microbicide field continues to evolve, we must harness the knowledge gained from unsuccessful and successful clinical trials and development programs to continuously enhance our preclinical development algorithms.

Phase I trial of cancer vaccine with multiple peptides derived from novel onco-antigen and anti-angiogenic antigens for patients with advanced non-small cell lung cancer (NSCLC).

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e13015-e13015
Author(s):  
Hiroyuki Suzuki ◽  
Takeo Hasegawa ◽  
Jun Ohsugi ◽  
Mika Hoshino ◽  
Mitsunori Higuchi ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Clinical Trials ◽  
Phase I ◽  
Phase I Trial ◽  
Survival Rates ◽  
Peptide Vaccine ◽  
Phase I Clinical Trials ◽  
Two Phase ◽  
Immunological Responses ◽  
Clinical Responses

e13015 Background: Two phase I clinical trials were conducted on patients with advanced or recurrent NSCLC to evaluate the safety, immunogenicity and clinical response of a multiple peptide vaccine that incorporates four epitope peptides. This vaccine is comprised of novel HLA-A24-restricted oncoantigens, including two of the following three peptides; up-regulated lung cancer 10 (URLC10), TTK protein kinase (TTK) and cell division associated 1 (CDCA1), in addition to peptides derived from vascular endothelial growth factor receptor 1 (VEGFR1) and 2 (VEGFR2). Methods: Peptides derived from URLC10, TTK, VEGFR1 and VEGFR2 were tested in Trial 1, while peptides derived from URLC10, CDCA1, VEGFR1 and VEGFR2 were tested in Trial 2. Fifteen HLA-24-positive patients with NSCLC who had not responded to standard therapy were enrolled in this classic 3 patient per dose per cohort phase I trial, designed with varying dosages (Trial 1; 0.5mg, 1mg and 3mg, Trial 2; 1mg, 3mg). Vaccines were administered weekly by subcutaneous injection into patients’ axillary region with Montanide ISA-51 incomplete Freund’s adjuvant until progressive disease occurred and/or patients refused further treatment. Immunological responses were evaluated by INF-gamma ELiSPOT assays. Results: Vaccinations were well-tolerated withno severe treatment-associated adverse events. Specific T cell responses were induced in all patients against at least one epitope peptide. However, weak immunological responses were found in the 0.5mg group compared with the 1mg and 3mg groups in Trial 1, therefore the 0.5mg group was excluded in Trial 2. In terms of clinical responses, no complete and partial responses were found, however 9 of 15 patients (60 %) were categorized with stable disease. The median overall survival time was 13.2 months, while 1- and 2-year survival rates were 52.5% and 32.8% respectively. Conclusions: Multiple peptide vaccination therapy using four novel peptides was safe, and could possibly be effective in extending the patients’ survival. These encouraging immunological and clinical responses could provide a case for further stages of clinical trials.

Ingested Type I Interferon: State of the Art as Treatment for Autoimmunity

2002 ◽  
Vol 227 (11) ◽  
pp. 981-988 ◽  
Author(s):  
Staley A. Brod
Keyword(s):  
Rheumatoid Arthritis ◽  
Multiple Sclerosis ◽  
Clinical Trials ◽  
Type 1 Diabetes ◽  
Phase I ◽  
Phase I Trial ◽  
Type I Interferon ◽  
Type I ◽  
Ifn Γ

We have proposed a unifying hypothesis of the etiopathogenesis of autoimmunity that defines autoimmunity as a type I interferon (IFN) immunodeficiency syndrome. We have examined toxicity and potential efficacy in three phase I (type 1 diabetes, rheumatoid arthritis, multiple sclerosis) and one phase II clinical trials in multiple sclerosis. In a phase I open-label trial in type 1 diabetes, ingested IFN-α preserved residual β-cell function in recent onset patients. In a second phase I trial, treatment of rheumatoid arthritis with ingested IFN-α reduced the secretion of interleukin (IL)-1, a pro-inflammatory cytokine. In a third phase I trial in multiple sclerosis, there was a significant decrease in peripheral blood mononuclear cell IL-2 and IFN-γ production after ingesting IFN-α. In a phase II randomized, placebo-controlled, double-blind trial in multiple sclerosis, 10,000 IU ingested IFN-α significantly decreased gadolinium enhancements compared with the placebo group at month 5. Tumor necrosis factor-α and IFN-γ cytokine secretion in the 10,000 IU group at month 5 showed a significant decrease that corresponded with the effect of ingested IFN-α on decreasing gadolinium enhancements. Ingested IFN-α was not toxic in any of these clinical trials. These studies suggest that ingested IFN-α may have a potential role in the treatment of autoimmunity.

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