The original purpose of vaginally applied microbicides was to slow down the HIV epidemic among the population until an effective vaccination was developed. Nowadays, antiretrovirals applied in the form of gels or vaginal rings are considered most prominent in this field and are tested via vaginal or, rarely, rectal applications in numerous clinical studies (9 different antiretroviral drugs in 33 clinical studies, especially in Africa). Only tenofovir (1 % gel) and dapivirine (25 mg in vaginal ring) progressed into the phase III clinical testing. Their efficiency depended on the user´s strict adherence to the application regimen (for tenofovir 54 %, for dapivirine 61 % in participants over 25 years of age). Despite this, they are expected to be important and effective tools of preventive medicine in the near future. This review summarizes the results obtained during long-term clinical testing (2005-2018) of antiretroviral drugs against vaginal and rectal transmission of HIV infection.
- MeSH
- antikoncepční prostředky ženské virologie MeSH
- antiretrovirové látky terapeutické užití MeSH
- HIV infekce farmakoterapie MeSH
- klinické zkoušky, fáze III jako téma MeSH
- lidé MeSH
- rektum virologie MeSH
- vagina virologie MeSH
- Check Tag
- lidé MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
High-risk human papillomavirus (hrHPV) infection is a cause of cervical cancer development. The addition of hrHPV testing to cervical cancer screening and monitoring of cervical intraepithelial neoplasia treatment improves the efficacy of screening and treatment, respectively. Self-sampling for hrHPV testing seems a promising tool for increasing patient participation in cervical cancer screening. In this project, 1198 cervical swabs obtained by physicians and 176 cervicovaginal swabs obtained by self-sampling (not collected in parallel) were analyzed for the presence of 14 hrHPV genotypes using three commercially available assays in comparison. HPV DNA was detected in 21.2% of all samples (21% of cervical swabs and 22.7% of cervicovaginal swabs). The cobas 4800 HPV Test was the most sensitive (0.983) and specific (0.992) for hrHPV detection overall. The PapilloCheck HPV-Screening and LMNX Genotyping Kit HPV GP had comparable specificity with that of the cobas (0.989 and 0.955, respectively), but lesser sensitivity (0.897 and 0.909, respectively). In physician-obtained cervical swabs, the cobas showed the highest sensitivity and specificity (0.980 and 0.994, respectively) for hrHPV detection, whereas in cervicovaginal swabs, the cobas had the highest sensitivity (1.00), but the PapilloCheck had the highest specificity (0.993). In conclusion, all of the detection methods evaluated were highly sensitive and specific for hrHPV detection from both clinician-collected cervical swabs and self-sampled cervicovaginal swabs.
- MeSH
- DNA virů analýza genetika MeSH
- dospělí MeSH
- genotypizační techniky metody MeSH
- infekce papilomavirem diagnóza virologie MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- nádory děložního čípku virologie MeSH
- Papillomaviridae genetika MeSH
- reagenční diagnostické soupravy * MeSH
- senioři MeSH
- senzitivita a specificita MeSH
- vagina virologie MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- srovnávací studie MeSH
Topical microbicides to stop sexually transmitted diseases, such as herpes simplex virus type 2 (HSV-2), are urgently needed. The emerging field of nanotechnology offers novel suitable tools for addressing this challenge. Our objective was to study, in vitro and in vivo, antiherpetic effect and antiviral mechanisms of several polyanionic carbosilane dendrimers with anti-HIV-1 activity to establish new potential microbicide candidates against sexually transmitted diseases. Plaque reduction assay on Vero cells proved that G2-S16, G1-S4, and G3-S16 are the dendrimers with the highest inhibitory response against HSV-2 infection. We also demonstrated that our dendrimers inhibit viral infection at the first steps of HSV-2 lifecycle: binding/entry-mediated events. G1-S4 and G3-S16 bind directly on the HSV-2, inactivating it, whereas G2-S16 adheres to host cell-surface proteins. Molecular modeling showed that G1-S4 binds better at binding sites on gB surface than G2-S16. Significantly better binding properties of G1-S4 than G2-S16 were found in an important position for affecting transition of gB trimer from G1-S4 prefusion to final postfusion state and in several positions where G1-S4 could interfere with gB/gH-gL interaction. We demonstrated that these polyanionic carbosilan dendrimers have a synergistic activity with acyclovir and tenofovir against HSV-2, in vitro. Topical vaginal or rectal administration of G1-S4 or G2-S16 prevents HSV-2 transmission in BALB/c mice in values close to 100%. This research represents the first demonstration that transmission of HSV-2 can be blocked by vaginal/rectal application of G1-S4 or G2-S16, providing a step forward to prevent HSV-2 transmission in humans.
- MeSH
- acyklovir farmakologie MeSH
- antiinfekční látky farmakologie MeSH
- antivirové látky farmakologie MeSH
- aplikace rektální MeSH
- Cercopithecus aethiops MeSH
- dendrimery chemie MeSH
- epitelové buňky účinky léků virologie MeSH
- herpes simplex MeSH
- koncentrace vodíkových iontů MeSH
- lidé MeSH
- lidský herpesvirus 2 účinky léků MeSH
- molekulární modely MeSH
- myši inbrední BALB C MeSH
- polymery chemie MeSH
- rektum účinky léků virologie MeSH
- silany chemie MeSH
- tenofovir farmakologie MeSH
- vagina účinky léků virologie MeSH
- Vero buňky MeSH
- virové proteiny metabolismus MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
