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Best Practice & Research. Clinical... Aug 2012The reduction in human immunodeficiency virus (HIV) infection in women demonstrated by pericoital use of tenofovir gel has encouraged the continued development of... (Review)
Review
The reduction in human immunodeficiency virus (HIV) infection in women demonstrated by pericoital use of tenofovir gel has encouraged the continued development of microbicides. Novel approaches include new ways to deliver tenofovir, as well as products that contain different antiretroviral drugs, either as single agents or as combinations of antiretroviral drugs. Indeed, emphasis has renewed on the development of multipurpose prevention technologies, products designed to address multiple sexually transmitted infections. Dual-purpose contraceptive antiretroviral products are also being designed to prevent HIV and pregnancy. Since consistent and correct use of these products will be critical to their effectiveness, the active pharmaceutical ingredients must be delivered in acceptable vaginal dosage forms, such as gels, films and sustained-release vaginal rings. The development of different dosage forms will help ensure that women can find a method to protect themselves from HIV, pregnancy, and potentially other sexually transmitted infections.
Topics: Administration, Intravaginal; Anti-Infective Agents; Contraceptive Agents; Contraceptive Devices, Female; Drugs, Investigational; Female; Forecasting; HIV; HIV Infections; Humans; Pregnancy
PubMed: 22406260
DOI: 10.1016/j.bpobgyn.2012.02.001 -
AIDS (London, England) May 2003Abandoning condoms for microbicides is termed 'condom migration'. This study estimated the reduction in condom use that can be tolerated following the introduction of an... (Review)
Review
OBJECTIVES
Abandoning condoms for microbicides is termed 'condom migration'. This study estimated the reduction in condom use that can be tolerated following the introduction of an HIV- and sexually transmitted disease (STD)-efficacious microbicide without increasing an individual's risk of HIV infection, and explored how microbicide use affects HIV-risk.
DESIGN
Development of a static mathematical model to compare how different combinations of condom and microbicide use affect individual risk of HIV and STD infection at a particular point in time.
METHODS
The model is used to identify the 'break-even point' at which any increased risk associated with condom migration is counter-balanced by the protection afforded with microbicides. Data from Benin is used as a case-example.
RESULTS
Considering a 50% HIV- and STD-efficacious microbicide, groups that use condoms with 25% consistency or less could cease using condoms without increasing their risk if they use microbicides in 50% or more of sex acts. However, migration may increase risk if the initial condom-consistency is high (> 70%) and microbicide-consistency is low (< 50% of non-condom-protected acts). For the Benin case-example, if condoms are initially used in 70% or less of sex acts, and if consistency of condom use is sustained following microbicide introduction, there will be a 20% or greater reduction in HIV-risk if the microbicide is used in 50% of non-condom-protected sex acts.
CONCLUSIONS
There are likely to be many situations in which the benefits of microbicide use outweigh the negative impact of condom migration, and where microbicides could substantially reduce HIV-risk.
Topics: Administration, Intravaginal; Anti-Infective Agents, Local; Antiviral Agents; Condoms; Female; HIV Infections; Humans; Male; Models, Theoretical; Risk Assessment; Risk-Taking; Safe Sex; Sexual Behavior
PubMed: 12819525
DOI: 10.1097/00002030-200305230-00015 -
Current Medicinal Chemistry 2007There is an urgent clinical need to research novel methods of fertility control that are also protective against sexually transmitted diseases (STDs) such as the human... (Review)
Review
There is an urgent clinical need to research novel methods of fertility control that are also protective against sexually transmitted diseases (STDs) such as the human immunodeficiency virus (HIV) or Chlamydia. The most obvious way to generate such a dual-purpose contraceptive method would be to develop safe, effective spermicides that were also active against a wide range of pathogenic organisms. The currently available formulations such as nonoxynol-9, gramicidin and benzalkonium chloride are effective spermicides but are toxic to the vaginal epithelium and do not provide protection against STDs. Over 60 agents are in clinical trials as potentially safer topical spermicides and/or microbicides. Compounds that have reached this stage of development include acid buffers, detergents, dendrimers, non-nucleoside reverse transcriptase inhibitors and anionic polymers. In addition, a number of potential spermicides/microbicides are the subject of preclinical investigation, including beta-cyclodextrin, cyanovirin, porphyrins, cyclotriazadisulfonamides, dermaseptins, short-interfering RNA (siRNA) and HIV antibodies. The chemical principles underlying these disparate approaches and potential avenues for future investigation are discussed.
Topics: Administration, Topical; Anti-Infective Agents; Contraception; Female; Humans; Male; Sexually Transmitted Diseases; Spermatocidal Agents
PubMed: 17346162
DOI: 10.2174/092986707780090972 -
Current Opinion in HIV and AIDS Jul 2010Microbicide research has been in the forefront of scientific literature in recent months. Results of large-scale clinical trials have been announced with resultant... (Review)
Review
PURPOSE OF REVIEW
Microbicide research has been in the forefront of scientific literature in recent months. Results of large-scale clinical trials have been announced with resultant investigations into the factors that may have contributed to the disappointing outcomes of the most promising candidates. This review takes into consideration clinical, basic scientific and behavioural research published on microbicides in the past 12-18 months.
RECENT FINDINGS
Two trials testing PRO 2000, a sulphated polymer, suggested that it has no effect on HIV. Basic science research revealed several facts such as the loss of antiviral activity of microbicides in the presence of seminal plasma. Methodological models suggested that dilution factors might impact on measures of efficacy. Advancement into safety testing of highly specific antiretroviral products such as tenofovir and UC781 for both rectal and vaginal use shows promise. Development of drug delivery systems such as intravaginal rings may alleviate some of the adherence challenges faced when using coitally dependant products.
SUMMARY
In the recent past, microbicide research has had disappointing outcomes. However, it has also provided a better understanding of factors that may reduce effectiveness of promising products, enabling the field to be better equipped to select and test new products.
Topics: Anti-Infective Agents; Biomedical Research; Clinical Trials as Topic; Disease Transmission, Infectious; Disinfection; HIV Infections; Humans; Treatment Outcome
PubMed: 20543607
DOI: 10.1097/COH.0b013e32833a9f66 -
American Journal of Public Health Jul 2004With more than 60 potential microbicides being assessed in preclinical or clinical trials, most attention has been centered on products intended for topical application,... (Review)
Review
With more than 60 potential microbicides being assessed in preclinical or clinical trials, most attention has been centered on products intended for topical application, with much less research conducted on the applicators that will be used to deliver the microbicides. However, applicator design relates to safety, efficacy, and acceptability. As the foundation for a more systematic approach to evaluating and possibly improving designs for topical microbicide applicators, we conducted a literature review and a series of interviews with microbicide developers, trial investigators, and trial sponsors. Our findings indicate that issues concerning applicator safety, reuse, and cost warrant further investigation.
Topics: Administration, Intravaginal; Anti-Infective Agents, Local; Antiviral Agents; Clinical Trials as Topic; Equipment Design; Equipment Reuse; Female; HIV Infections; Humans; Needs Assessment; Safety; Vaginal Creams, Foams, and Jellies
PubMed: 15226124
DOI: 10.2105/ajph.94.7.1089 -
European Journal of Medical Research Jan 2011Women and girls are especially vulnerable to HIV infection in sub-Saharan Africa, and in some of those countries, prevalence among young women can be up to 3 times... (Review)
Review
Women and girls are especially vulnerable to HIV infection in sub-Saharan Africa, and in some of those countries, prevalence among young women can be up to 3 times higher than among men of the same age. Effective HIV prevention options for women are clearly needed in this setting. Several ARV-based vaginal microbicides are currently in development for prevention of HIV transmission to women and are discussed here. The concept of pre-exposure prophylaxis for the prevention of HIV transmission to women is introduced.
Topics: Adenine; Administration, Intravaginal; Adult; Africa South of the Sahara; Anti-HIV Agents; Anti-Infective Agents; Clinical Trials as Topic; Cyclohexanes; Drug Discovery; Female; HIV Infections; Humans; Male; Maraviroc; Organophosphonates; Pyridines; Pyrimidines; Tenofovir; Triazoles; Urea
PubMed: 21345763
DOI: 10.1186/2047-783x-16-1-1 -
International Journal of Nanomedicine 2007Microbicides are compounds that applied vaginally or rectally, protect the user from sexually transmitted infections. Although no commercial product is yet available,... (Review)
Review
Microbicides are compounds that applied vaginally or rectally, protect the user from sexually transmitted infections. Although no commercial product is yet available, many candidates are under development. A leading candidate, VivaGel (SPL7013 Gel) is the product of nanotechnology. The active ingredient is SPL7013, a dendrimer that was designed specifically with HIV and HSV antiviral activity and human safety in mind. SPL7013 has demonstrated efficacy against human immunodeficiency virus and herpes simplex virus in in vitro and animal models. VivaGel appears to be well tolerated in both animals and humans. This review summarizes the studies of VivaGel and its active ingredient, SPL7013.
Topics: Anti-Infective Agents, Local; Antiviral Agents; Clinical Trials as Topic; Dendrimers; HIV Infections; Herpes Simplex; Humans; Polylysine
PubMed: 18203424
DOI: No ID Found -
Journal of the International AIDS... 2015Microbicides were conceptualized as a product that could give women increased agency over HIV prevention. However, gender-related norms and inequalities that place women... (Review)
Review
INTRODUCTION
Microbicides were conceptualized as a product that could give women increased agency over HIV prevention. However, gender-related norms and inequalities that place women and girls at risk of acquiring HIV are also likely to affect their ability to use microbicides. Understanding how gendered norms and inequalities may pose obstacles to women's microbicide use is important to inform product design, microbicide trial implementation and eventually microbicide and other antiretroviral-based prevention programmes. We reviewed published vaginal microbicide studies to identify gender-related factors that are likely to affect microbicide acceptability, access and adherence. We make recommendations on product design, trial implementation, positioning, marketing and delivery of microbicides in a way that takes into account the gender-related norms and inequalities identified in the review.
METHODS
We conducted PubMed searches for microbicide studies published in journals between 2000 and 2013. Search terms included trial names (e.g. "MDP301"), microbicide product names (e.g. "BufferGel"), researchers' names (e.g. "van der Straten") and other relevant terms (e.g. "microbicide"). We included microbicide clinical trials; surrogate studies in which a vaginal gel, ring or diaphragm was used without an active ingredient; and hypothetical studies in which no product was used. Social and behavioural studies implemented in conjunction with clinical trials and surrogate studies were also included. Although we recognize the importance of rectal microbicides to women, we did not include studies of rectal microbicides, as most of them focused on men who have sex with men. Using a standardized review template, three reviewers read the articles and looked for gender-related findings in key domains (e.g. product acceptability, sexual pleasure, partner communication, microbicide access and adherence).
RESULTS AND DISCUSSION
The gendered norms, roles and relations that will likely affect women's ability to access and use microbicides are related to two broad categories: norms regulating women's and men's sexuality and power dynamics within intimate relationships. Though norms about women's and men's sexuality vary among cultural contexts, women's sexual behaviour and pleasure are typically less socially acceptable and more restricted than men's. These norms drive the need for woman-initiated HIV prevention, but also have implications for microbicide acceptability and how they are likely to be used by women of different ages and relationship types. Women's limited power to negotiate the circumstances of their intimate relationships and sex lives will impact their ability to access and use microbicides. Men's role in women's effective microbicide use can range from opposition to non-interference to active support.
CONCLUSIONS
Identifying an effective microbicide that women can use consistently is vital to the future of HIV prevention for women. Once such a microbicide is identified and licensed, positioning, marketing and delivering microbicides in a way that takes into account the gendered norms and inequalities we have identified would help maximize access and adherence. It also has the potential to improve communication about sexuality, strengthen relationships between women and men and increase women's agency over their bodies and their health.
Topics: Administration, Intravaginal; Adult; Anti-Infective Agents; Female; HIV Infections; Humans; Interpersonal Relations; Male; Sexual Behavior; Sexual Partners; Vaginal Creams, Foams, and Jellies
PubMed: 26700845
DOI: 10.7448/IAS.18.1.20536 -
AIDS Patient Care and STDs Jan 2003Microbicides, the compounds and formulations that can prevent transmission of sexually transmitted diseases (STDs)/HIV are being pursued actively as a promising AIDS... (Review)
Review
Microbicides, the compounds and formulations that can prevent transmission of sexually transmitted diseases (STDs)/HIV are being pursued actively as a promising AIDS intervention. The drug development chain for a topical microbicide differs significantly from that of any systemic or topical compound/formulation regarding to time line, cost, activities, and milestones. This is in part because of the lack of standard in vitro models to assess efficacy, and complex ethical issues in clinical trials of microbicides. Several factors, including changes in the physiology of the cervix and vagina with age and menstrual cycle, intercourse, as well as leakage of the formulation from the vagina may affect their design, development, and performance. Selection and development of optimal microbicide delivery systems (gel/cream, pessary, film, tablet, foam, etc.), their inactive ingredients, manufacturing details, and packaging system are dependent on the properties of active drug, or their preformulation parameters (PP). The PP of the active drug substance needs to be evaluated in initial stages of drug discovery and development so that the most suitable delivery system can be selected. Some PP of microbicide agents include physical state, organoleptic properties (color, odor, appearance, taste, etc.), molecular weight, aqueous solubility, hygroscopicity, acidity/alkalinity, permeability and absorption characteristics, stability in solid/solution state, and inherent bioadhesiveness. Thus, a well-coordinated, planned, and implemented preformulation program can help in not only accelerating microbicide formulation development, but also to minimize unforeseen failures in subsequent stages of the development. The objective of this review is to highlight the significance of PP, suggesting a systematic preformulation program.
Topics: Administration, Intravaginal; Anti-Infective Agents; Chemistry, Pharmaceutical; Drug Approval; Female; Humans; Male; Sexually Transmitted Diseases
PubMed: 12614517
DOI: 10.1089/108729103321042881 -
PloS One 2013Pregnancy is contraindicated in vaginal microbicide trials for the prevention of HIV infection in women due to the unknown maternal and fetal safety of the microbicides.... (Meta-Analysis)
Meta-Analysis Review
INTRODUCTION
Pregnancy is contraindicated in vaginal microbicide trials for the prevention of HIV infection in women due to the unknown maternal and fetal safety of the microbicides. Women who become pregnant are taken off the microbicide during pregnancy period but this result in reduction of the power of the trials. Strategies to reduce the pregnancy rates require an understanding of the incidence and associated risk factors of pregnancy in microbicide trials. This systematic review estimates the overall incidence rate of pregnancy in microbicide trials and describes the associated risk factors.
METHODS
A comprehensive literature search was carried out to identify eligible studies from electronic databases and other sources. Two review authors independently selected studies and extracted relevant data from included studies. Meta-analysis of incidence rates of pregnancy was carried out and risk factors of pregnancy were reported narratively.
RESULTS
Fifteen studies reporting data from 10 microbicide trials (N=27,384 participants) were included. A total of 4,107 participants (15.0%) fell pregnant and a meta-analysis of incidence rates of pregnancy from 8 microbicide trials (N=25,551) yielded an overall incidence rate of 23.37 (95%CI: 17.78 to 28.96) pregnancies per 100 woman-years. However, significant heterogeneity was detected. Hormonal injectable, intra-uterine device (IUD) or implants or sterilization, older age, more years of education and condom use were associated with lower pregnancy. On the other hand, living with a man, history of pregnancy, self and partner desire for future baby, oral contraceptive use, increased number of unprotected sexual acts and inconsistent use of condoms were associated with higher pregnancy.
CONCLUSIONS
The incidence rate of pregnancy in microbicide trials is high and strategies for its reduction are urgently required in order to improve the sample size and power of these trials.
Topics: Anti-Infective Agents; Clinical Trials as Topic; Female; HIV Infections; Humans; Incidence; Pregnancy; Risk Factors; Vagina
PubMed: 24130827
DOI: 10.1371/journal.pone.0077014