摘要 :
Objectives: Develop and test a theoretical acceptability model for the Nestorone(R)/ethinyl estradiol contraceptive vaginal ring (CVR); explore whether domains of use within the model predict satisfaction, method adherence and CVR continuation.
摘要 :
The transmission of both cell-free and cell-associated immunodeficiency viruses has been demonstrated directly in multiple animal species and possibly occurs in humans, as suggested by genotyping of the infecting human immunodefic...
展开
The transmission of both cell-free and cell-associated immunodeficiency viruses has been demonstrated directly in multiple animal species and possibly occurs in humans, as suggested by genotyping of the infecting human immunodeficiency virus (HIV) in acutely infected women and in semen from their partners. Therefore, a microbicide may need to block both mechanisms of HIV transmission to achieve maximum efficacy. To date, most of the preclinical evaluation of candidate microbicides has been performed using cell-free HIV. New models of mucosal transmission of cell-associated HIV are needed to evaluate candidate microbicide performance. The MIV-150/ zinc acetate/carrageenan (MZC) gel protects Depo-Provera-treated macaques against cell-free simian-human immunodeficiency virus reverse transcriptase (SHIV-RT) infection when applied vaginally up to 8 h before challenge. We recently demonstrated the potent activity of MZC gel against cell-free SHIV-RT in macaque vaginal explants. In the current study, we established a cell-associated SHIV-RT infection model of macaque vaginal tissues and tested the activity of MZC gel in this model. MZC gel protected tissues against cell-associated SHIV-RT infection when present at the time of viral exposure or when applied up to 4 days prior to viral challenge. These data support clinical testing of the MZC gel. Overall, our ex vivo model of cell-associated SHIV-RT infection in macaque vaginal mucosa complements the cell-free infection models, providing tools for prioritization of products that block both modes of HIV transmission.
收起
摘要 :
Our recent phase 1 trial demonstrated that PC-1005 gel containing 50 mu M MIV-150, 14mMzinc acetate dihydrate, and carrageenan (CG) applied daily vaginally for 14 days is safe and well tolerated. Importantly, cervicovaginal lavage...
展开
Our recent phase 1 trial demonstrated that PC-1005 gel containing 50 mu M MIV-150, 14mMzinc acetate dihydrate, and carrageenan (CG) applied daily vaginally for 14 days is safe and well tolerated. Importantly, cervicovaginal lavage fluid samples (CVLs) collected 4 or 24 h after the last gel application inhibited HIV-1 and human papillomavirus (HPV) in cell-based assays in a dose-dependent manner (MIV-150 for HIV-1 and CG for HPV). Herein we aimed to determine the anti-HIV and anti-herpes simplex virus 2 (anti-HSV-2) activity of PC-1005 in human cervical explants after in vitro exposure to the gel and to CVLs from participants in the phase 1 trial. Single HIV-1(BaL) infection and HIV-1(BaL)-HSV-2 coinfection explant models were utilized. Coinfection with HSV-2 enhanced tissue HIV-1(BaL) infection. In vitro exposure to PC-1005 protected cervical mucosa against HIV1(BaL) (up to a 1: 300 dilution) in single-challenge and cochallenge models. CG gel (PC-525) provided some barrier effect against HIV-1(BaL) at the 1: 100 dilution in a single-challenge model but not in the cochallenge model. Both PC-1005 and PC-525 at the 1: 100 dilution inhibited HSV-2 infection, pointing to a CG-mediated protection. MIV-150 and CG in CVLs inhibited HIV (single- challenge or cochallenge models) and HSV-2 infections in explants in a dose-dependent manner (P< 0.05). Stronger inhibition of HIV-1 infection by CVLs collected 4 h after the last gel administration was observed compared to infection detected in the presence of baseline CVLs. The anti-HIV and anti-HSV-2 activity of PC-1005 gel in vitro and CVLs in human ectocervical explants supports the further development of PC-1005 gel as a broad-spectrum on-demand microbicide.
收起
摘要 :
ObjectiveNumerous studies have documented an inverse association between years of schooling attained, particularly by women, and reduced maternal, infant and child mortality. However, if factors affecting educational attainment ma...
展开
ObjectiveNumerous studies have documented an inverse association between years of schooling attained, particularly by women, and reduced maternal, infant and child mortality. However, if factors affecting educational attainment many of which are unobservable, e.g. motivation and genetic endowment also affect the likelihood of engaging in behaviours that enhance health, then assumed effects of schooling will be inflated in analyses that do not address this endogeneity. This systematic review assesses evidence for a causal link between education and maternal and child health in low and middle-income countries.
收起
摘要 :
<abstract_text><p>While the contributions of science, biomedicine, and engineering to contraceptive development offer wonder and promise to the community, what inspires many of us in the not-for-profit sector about the process of ...
展开
<abstract_text><p>While the contributions of science, biomedicine, and engineering to contraceptive development offer wonder and promise to the community, what inspires many of us in the not-for-profit sector about the process of contraceptive product development is the integration of consultations with users, providers and policy makers, good clinical and manufacturing practice in product design and development, and the delivery of approved products at affordable prices to those in greatest need. The commitment to have an impact on the reproductive lives of women and men along with the ethical principles embedded in this process of achieving safe, effective, and acceptable options include the respect for persons, i.e., eventual users, beneficence for those using the product and justice in ensuring that it is available to those who are most vulnerable, including those in developing countries. It is the inspiration that drives the scientists and developers to produce public benefit and additional social value.</p></abstract_text>
收起
摘要 :
The COVID-19 pandemic has exposed the vulnerability of global contraception provision, exacerbating the barriers to access reproductive health services, leading to suspension of clinical services and disruption of supply chains. C...
展开
The COVID-19 pandemic has exposed the vulnerability of global contraception provision, exacerbating the barriers to access reproductive health services, leading to suspension of clinical services and disruption of supply chains. Critical to combatting this crisis is the expansion of healthcare to include self-care ap-proaches to de-medicalize contraception and increase an individual's agency in determining what method they use, when they use it, and where they obtain it. Expanding the mix of self-administered contra-ceptives is essential for ensuring choice, access, and availability. We highlight advances in the self-care movement and actions needed to strengthen self-management approaches to maximize our chances of preventing a reproductive health crisis. (C) 2021 Elsevier Inc. All rights reserved.
收起
摘要 :
The Population Council's microbicide gel MZC (also known as PC-1005) containing MIV-150 and zinc acetate dihydrate (ZA) in carrageenan (CG) has shown promise as a broad-spectrum microbicide against HIV, herpes simplex virus (HSV),...
展开
The Population Council's microbicide gel MZC (also known as PC-1005) containing MIV-150 and zinc acetate dihydrate (ZA) in carrageenan (CG) has shown promise as a broad-spectrum microbicide against HIV, herpes simplex virus (HSV), and human papillomavirus. Previous data show antiviral activity against these viruses in cell-based assays, prevention of vaginal and rectal simianhuman immunodeficiency virus reverse transcriptase (SHIV-RT) infection, and reduction of vaginal HSV shedding in rhesus macaques and also excellent antiviral activity against HSV and human papillomavirus in murine models. Recently, we demonstrated that MZC is safe and effective against SHIV-RT in macaque vaginal explants. Here we established models of ex vivo SHIV-RT/HSV-2 coinfection of vaginal mucosa and SHIV-RT infection of rectal mucosa in macaques (challenge of rectal mucosa with HSV-2 did not result in reproducible tissue infection), evaluated antiviral activity of MZC, and compared quantitative polymerase chain reaction (PCR) and enzyme-linked immunosorbent assay readouts for monitoring SHIV-RT infection. MZC (at nontoxic dilutions) significantly inhibited SHIV-RT in vaginal and rectal mucosas and HSV-2 in vaginal mucosa when present during viral challenge. Analysis of SHIV-RT infection and MZC activity by 1-step simian immunodeficiency virus gag quantitative RT-PCR and p27 enzyme-linked immunosorbent assay demonstrated similar virus growth dynamics and MZC activity by both methods and higher sensitivity of quantitative RT-PCR. Our data provide more evidence that MZC is a promising dual compartment multipurpose prevention technology candidate.
收起
摘要 :
Extensive preclinical evaluation of griffithsin (GRFT) has identified this lectin to be a promising broad-spectrum microbicide. We set out to explore the antiviral properties of a GRFT and carrageenan (CG) combination product agai...
展开
Extensive preclinical evaluation of griffithsin (GRFT) has identified this lectin to be a promising broad-spectrum microbicide. We set out to explore the antiviral properties of a GRFT and carrageenan (CG) combination product against herpes simplex virus 2 (HSV-2) and human papillomavirus (HPV) as well as determine the mechanism of action (MOA) of GRFT against both viruses. We performed the experiments in different cell lines, using time-of-addition and temperature dependence experiments to differentiate inhibition of viral attachment from entry and viral receptor internalization. Surface plasmon resonance (SPR) was used to assess GRFT binding to viral glycoproteins, and immunoprecipitation and immunohistochemistry were used to identify the specific glycoprotein involved. We determined the antiviral activity of GRFT against HSV-2 to be a 50% effective concentration (EC50) of 230 nM and provide the first evidence that GRFT has moderate anti-HPV activity (EC50 = 0.429 to 1.39 mu M). GRFT blocks the entry of HSV-2 and HPV into target cells but not the adsorption of HSV-2 and HPV onto target cells. The results of the SPR, immunoprecipitation, and immunohistochemistry analyses of HSV-2 combined suggest that GRFT may block viral entry by binding to HSV-2 glycoprotein D. Cell-based assays suggest anti-HPV activity through alpha(6) integrin internalization. The GRFT-CG combination product but not GRFT or CG alone reduced HSV-2 vaginal infection in mice when given an hour before challenge (P = 0.0352). While GRFT significantly protected mice against vaginal HPV infection when dosed during and after HPV16 pseudovirus challenge (P < 0.026), greater CG-mediated protection was afforded by the GRFT-CG combination for up to 8 h (P < 0.0022). These findings support the development of the GRFT-CG combination as a broad-spectrum microbicide.
收起
摘要 :
Sexually transmitted infections like HIV, HPV, and HSV-2, as well as unplanned pregnancy, take a huge toll on women worldwide. Woman-initiated multipurpose prevention technologies that contain antiviral/antibacterial drugs (microb...
展开
Sexually transmitted infections like HIV, HPV, and HSV-2, as well as unplanned pregnancy, take a huge toll on women worldwide. Woman-initiated multipurpose prevention technologies that contain antiviral/antibacterial drugs (microbicides) and a contraceptive to simultaneously target sexually transmitted infections and unplanned pregnancy are being developed to reduce these burdens. This review will consider products that are applied topically to the vagina. Rectally administered topical microbicides in development for receptive anal intercourse are outside the scope of this review. Microbicide and microbicide/contraceptive candidates must be rigorously evaluated in preclinical models of safety and efficacy to ensure that only candidates with favorable risk benefit ratios are advanced into human clinical trials. This review describes the comprehensive set of in vitro, ex vivo, and in vivo models used to evaluate the preclinical safety and antiviral efficacy of microbicide and microbicide/contraceptive candidates. (C) 2014 The Authors. Published by Elsevier B.V.
收起
原文获取