A5041327263- HIV/AIDS Research and Interventions
- HIV Research and Treatment
- Reproductive tract infections research
- HIV/AIDS drug development and treatment
- Herpesvirus Infections and Treatments
- Adolescent Sexual and Reproductive Health
- Pregnancy and Medication Impact
- HIV, Drug Use, Sexual Risk
- Syphilis Diagnosis and Treatment
- Virology and Viral Diseases
- Sex work and related issues
- Protein purification and stability
- Analytical Methods in Pharmaceuticals
- Reproductive System and Pregnancy
- Bladder and Urothelial Cancer Treatments
- Historical Economic and Social Studies
- Probiotics and Fermented Foods
- Transgenic Plants and Applications
- Microbial infections and disease research
- Gynecological conditions and treatments
- Clostridium difficile and Clostridium perfringens research
- Historical Psychiatry and Medical Practices
- Endometriosis Research and Treatment
- Advanced Drug Delivery Systems
- Urologic and reproductive health conditions
International Partnership for Microbicides
2010-2022
Job Performance Systems (United States)
2016
Kingston University
2003
Royal Marsden NHS Foundation Trust
1978
Royal Marsden Hospital
1978
The incidence of human immunodeficiency virus (HIV) infection remains high among women in sub-Saharan Africa. We evaluated the safety and efficacy extended use a vaginal ring containing dapivirine for prevention HIV 1959 healthy, sexually active women, 18 to 45 years age, from seven communities South Africa Uganda.In this randomized, double-blind, placebo-controlled, phase 3 trial, we randomly assigned participants 2:1 ratio receive rings either 25 mg or placebo. Participants inserted...
Heterosexual transmission of human immunodeficiency virus (HIV) remains the major route infection worldwide; thus, there is an urgent need for additional prevention strategies, particularly strategies that could be controlled by women, such as topical microbicides. Potential microbicide candidates must both safe and effective. Using cellular tissue explant models, we have evaluated activity nonnucleoside reverse transcriptase inhibitor (NNRTI) dapivirine a vaginal microbicide. In...
Women-initiated HIV-prevention products are urgently needed. To address this need, a trial was conducted to assess the safety and pharmacokinetics of silicone elastomer matrix vaginal ring containing 25 mg antiretroviral drug dapivirine when used continuously for 28 consecutive days.A double-blind, randomized, placebo-controlled in 16 healthy, HIV-negative women, 18-40 years age, who were randomized 1:1 use either active or matching placebo days. Participants followed during days after...
ABSTRACT Tenofovir gel (1%) is being developed as a microbicide for the prevention of human immunodeficiency virus (HIV) infection and has been shown to reduce transmission women by 39%. The also prevents in macaques when applied intravaginally or intrarectally prior challenge with simian-human (SHIV), but very little pharmacokinetic information available help extrapolate data humans thus inform future development activities. We have determined pharmacokinetics tenofovir following...
Dapivirine is a nonnucleoside reverse transcriptase inhibitor being developed as topical microbicide for the prevention of human immunodeficiency virus infection. The distribution radioactivity and drug in plasma vaginal, cervical, draining lymph node tissues was investigated after daily application vaginal gel formulation [14C]dapivirine to rhesus macaques. This preceded by preliminary study with rabbits. Following intravaginal administration ( approximately 0.1 mg/ml [15 microCi/ml])...
ABSTRACT When developing novel microbicide products for the prevention of HIV infection, preclinical safety program must evaluate not only active pharmaceutical ingredient but also product itself. To that end, we applied several relatively standard toxicology study methodologies to female sheep, incorporating an assessment pharmacokinetics, safety, tolerability, and local toxicity a dapivirine-containing human vaginal ring formulation (Dapivirine Vaginal Ring-004). We performed 3-month...
ABSTRACT Topical blockade of the gp41 fusogenic protein HIV-1 is one possible strategy by which microbicides could prevent HIV transmission, working early against infection, inhibiting viral entry into host cells. In this study, we examined potential fusion inhibitors (FIs) as candidate anti-HIV microbicides. Preclinical evaluation four FIs, C34, T20, T1249, and L'644, was performed using cellular ex vivo genital colorectal tissue explant models. Increased sustained activity detected for a...
Abstract Introduction Vaginal rings are a promising approach to provide woman‐centred, long‐acting HIV prevention strategy. Prior trials of 25 mg dapivirine (DPV) ring have shown favourable safety profile and approximately 30% risk reduction HIV‐1 infection. Extended duration replaced every three months may encourage user adherence, improve health service efficiency reduce cost overall. We evaluated safety, pharmacokinetics, adherence acceptability two three‐month with different DPV dosages,...
Receptive anal intercourse in both men and women is associated with the highest probability for sexual acquisition of HIV infection. As part a program to develop an effective prevention strategy, we performed ex-vivo preclinical evaluation determine efficacy multiple double combinations maraviroc (MVC) reverse transcriptase inhibitors (RTIs).The entry inhibitor, MVC, nucleotide RTI, tenofovir two non-nucleoside RTIs, UC781 TMC120 (dapivirine, DPV), were used double, against panel CCR5-using...
This article uses the broad concept of ‘improvement minds’ to refer idea improving people's sense morality, their ability and willingness reason, depth emotional experiences. Such an objective has been little explored in context history British Labour party. Yet, discussion it is worth integrating into histories party for two reasons. First, goal minds was a strand – though often unsystematically developed agendas many politicians, activists, thinkers. Secondly, very fact that strand, limits...
Background: The ex vivo challenge assay is a bio-indicator of drug efficacy and was utilized in this randomized, placebo controlled trial as one the exploratory endpoints. Fresh cryopreserved tissues were evaluated for human immunodeficiency virus (HIV) infection pharmacokinetic (PK)/pharmacodynamic (PD) relationships. Methods: HIV-negative women used vaginal rings containing 25 mg dapivirine (DPV)/100 maraviroc (MVC) (n = 12), DPV only MVC or 12) 28 days. Blood plasma, cervicovaginal fluid...
The potential of maraviroc (MVC), a small-molecule CCR5 antagonist, as candidate to prevent HIV-1 sexual transmission by oral or topical dosing has not yet been completely established. Using relevant cellular and mucosal tissue explant models, we show partial antiviral activity MVC when tested in multiple preclinical strategies.
Dapivirine (DPV), formulated as vaginal ring, demonstrated HIV risk reduction. MTN-026 explored DPV, rectal gel, for safety, pharmacokinetics (PK), and acceptability. HIV-uninfected men women aged 18-45 years were enrolled at United States Thailand sites randomized 2:1 to receive DPV 0.05% or placebo gel via applicator. A single-dose phase was followed by seven observed daily doses. Plasma fluid tissue from both rectum cervix collected baseline after the final dose over 72 h PK, ex-vivo...
Objective: Small molecule inhibitors able to bind gp120 and prevent CD4 + -induced HIV-1 envelope conformational change provide an important class of inhibitors. Currently, only Fostemsavir is approved for HAART, which makes this attractive candidates prevention. We assessed the activity DS003 (BMS-599793), analogue BMS-378806, in different mucosal tissues elucidated its mechanism action. Design: Preclinical analysis was performed with human tissue models as surrogates in-vivo activity....
The Ring Study demonstrated 35.1% human immunodeficiency virus type 1 (HIV-1) infection risk reduction among participants who used the Dapivirine vaginal ring-004 (DVR), whereas Extended Access and Monitoring (DREAM) trial, approximated a 62% reduction. observed non-nucleoside reverse-transcriptase inhibitor (NNRTI) resistance-associated mutations (RAMs) effects on viral susceptibility are described here.Population-based genotyping plasma samples collected longitudinally, next-generation...