Microbicide Use Research Articles

Engaging Male Partners in Women's Microbicide Use: Evidence from Clinical Trials and Implications for Future Research and Microbicide Introduction

AIDS Research and Human RetrovirusesVol. 30, No. S1 Microbicides: Male Partner Engagement and Sexual BehaviorsEngaging Male Partners in Women's Microbicide Use: Evidence from Clinical Trials and Implications for Future Research and Microbicide IntroductionMichele Lanham, Rose Wilcher, Elizabeth T. Montgomery, Robert Pool, Sidney Schuler, Rachel Lenzi, Barbara Friedland, Betty Njoroge, Elizabeth Bukusi, and Robyn DaytonMichele LanhamFHI 360, Social and Behavioral Health Sciences, Durham, NC, United StatesSearch for more papers by this author, Rose WilcherFHI 360, Research Utilization, Durham, NC, United StatesSearch for more papers by this author, Elizabeth T. MontgomeryRTI International, Women's Global Health Imperative, San Francisco, CA, United StatesSearch for more papers by this author, Robert PoolUniversity of Amsterdam, Centre for Social Science and Global Health, Amsterdam, NetherlandsSearch for more papers by this author, Sidney SchulerFHI 360, Social and Behavioral Health Sciences, Washington, DC, United StatesSearch for more papers by this author, Rachel LenziFHI 360, Social and Behavioral Health Sciences, Washington, DC, United StatesSearch for more papers by this author, Barbara FriedlandPopulation Council, HIV and AIDS Program, New York, NY, United StatesSearch for more papers by this author, Betty NjorogeKenya Medical Research Institute, Research Care and Training Program, Centre for Microbiology Research, Nairobi, KenyaSearch for more papers by this author, Elizabeth BukusiKenya Medical Research Institute, Research Care and Training Program, Centre for Microbiology Research, Nairobi, KenyaSearch for more papers by this author, and Robyn DaytonFHI 360, Research Utilization, Durham, NC, United StatesSearch for more papers by this authorPublished Online:30 Oct 2014https://doi.org/10.1089/aid.2014.5005.abstractAboutSectionsView articleView Full TextPDF/EPUB ToolsPermissionsDownload CitationsTrack CitationsAdd to favorites Back To Publication ShareShare onFacebookTwitterLinked InRedditEmail View article"Engaging Male Partners in Women's Microbicide Use: Evidence from Clinical Trials and Implications for Future Research and Microbicide Introduction." AIDS Research and Human Retroviruses, 30(S1), p. A9FiguresReferencesRelatedDetailsCited byOn-demand microbicide products: design matters6 June 2017 | Drug Delivery and Translational Research, Vol. 7, No. 6 Volume 30Issue S1Oct 2014 InformationCopyright 2014, Mary Ann Liebert, Inc.To cite this article:Michele Lanham, Rose Wilcher, Elizabeth T. Montgomery, Robert Pool, Sidney Schuler, Rachel Lenzi, Barbara Friedland, Betty Njoroge, Elizabeth Bukusi, and Robyn Dayton.Engaging Male Partners in Women's Microbicide Use: Evidence from Clinical Trials and Implications for Future Research and Microbicide Introduction.AIDS Research and Human Retroviruses.Oct 2014.A9-A9.http://doi.org/10.1089/aid.2014.5005.abstractPublished in Volume: 30 Issue S1: October 30, 2014PDF download

Interest in multipurpose prevention of HIV and pregnancy: perspectives of women, men, health professionals and community stakeholders in two vaginal gel studies in southern Africa.

The pipeline of vaginal microbicides for HIV prevention has expanded to include products for multipurpose prevention, but the interests of potential users and those advising on use have not been sufficiently investigated. Rather, assumptions about interest in multipurpose prevention technologies (MPTs) are inferred from what is known about acceptability and use of microbicides or contraceptives. This paper presents data on concerns and preferences for multipurpose prevention of HIV and pregnancy. Data were collected in two microbicide gel studies in Malawi and Zimbabwe. Participants were women using candidate vaginal products, their male partners, health professionals and community stakeholders. An individual interview was conducted with participants. Interviews were audio-recorded, transcribed, coded for content and analysed for key themes. Participants indicated strong interest in a vaginal HIV prevention product that could also prevent pregnancy. Reasons for this interest were convenience, problems with adverse effects with current contraceptive methods, concerns about long-term effects of contraceptives, and concerns about the health burdens of HIV infection during pregnancy. The main disadvantage of an MPT was recognition that while interest in preventing HIV is constant, contraceptive needs change over time. The study population indicated support for an MPT to prevent HIV and pregnancy. This support may be further strengthened if the product is also available for prevention of only HIV. Women and men will be more willing to use an MPT if they can be reassured that its use will have no long-term effect on fertility.

An effective intervention to reduce intravaginal practices among HIV-1 uninfected Kenyan women.

Intravaginal practices (IVP) are common among African women and are associated with HIV acquisition. A behavioral intervention to reduce IVP is a potential new HIV risk-reduction strategy. Fifty-eight HIV-1-uninfected Kenyan women reporting IVP and 42 women who denied IVP were followed for 3 months. Women using IVP attended a skill-building, theory-based group intervention occurring weekly for 3 weeks to encourage IVP cessation. Vaginal swabs at each visit were used to detect yeast, to detect bacterial vaginosis, and to characterize the vaginal microbiota. Intravaginal insertion of soapy water (59%) and lemon juice (45%) was most common among 58 IVP women. The group-counseling intervention led to a decrease in IVP from 95% (54/58) at baseline to 0% (0/39) at month 3 (p=0.001). After 3 months of cessation, there was a reduction in yeast on vaginal wet preparation (22% to 7%, p=0.011). Women in the IVP group were more likely to have a Lactobacillus iners-dominated vaginal microbiota at baseline compared to controls [odds ratio (OR), 6.4, p=0.006] without significant change in the microbiota after IVP cessation. The group counseling intervention was effective in reducing IVP for 3 months. Reducing IVP may be important in itself, as well as to support effective use of vaginal microbicides, to prevent HIV acquisition.

Engaging male partners in women's microbicide use: evidence from clinical trials and implications for future research and microbicide introduction.

IntroductionConstructively engaging male partners in women-centred health programs such as family planning and prevention of mother-to-child HIV transmission has resulted in both improved health outcomes and stronger relationships. Concerted efforts to engage men in microbicide use could make it easier for women to access and use microbicides in the future. This paper synthesizes findings from studies that investigated men's role in their partners’ microbicide use during clinical trials to inform recommendations for male engagement in women's microbicide use.MethodsWe conducted primary and secondary analyses of data from six qualitative studies implemented in conjunction with microbicide clinical trials in South Africa, Kenya, and Tanzania. The analyses included data from 535 interviews and 107 focus groups with trial participants, male partners, and community members to answer research questions on partner communication about microbicides, men's role in women's microbicide use, and potential strategies for engaging men in future microbicide introduction. We synthesized the findings across the studies and developed recommendations.ResultsThe majority of women in steady partnerships wanted agreement from their partners to use microbicides. Women used various strategies to obtain their agreement, including using the product for a while before telling their partners, giving men information gradually, and continuing to bring up microbicides until resistant partners acquiesced. Among men who were aware their partners were participating in a trial and using microbicides, involvement ranged from opposition to agreement/non-interference to active support. Both men and women expressed a desire for men to have access to information about microbicides and to be able to talk with a healthcare provider about microbicides.ConclusionsWe recommend counselling women on whether and how to involve their partners including strategies for gaining partner approval; providing couples’ counselling on microbicides so men have the opportunity to talk with providers; and targeting men with community education and mass media to increase their awareness and acceptance of microbicides. These strategies should be tested in microbicide trials, open-label studies, and demonstration projects to identify effective male engagement approaches to include in eventual microbicide introduction. Efforts to engage men must take care not to diminish women's agency to decide whether to use the product and inform their partners.

Community and research staff collaboration for development of materials to inform microbicide study participants in Africa.

IntroductionClinical trials of new vaginal products require careful communication with participants about trial requirements. Most microbicide trials have been multi-site studies conducted among women in sub-Saharan Africa, where literacy levels and understanding of scientific methods differ from those designing and conducting the trials. Microbicide trials require women to insert objects in their vagina and ensure they are present in the vagina during sex. For many women, this is a novel behaviour. These behaviours take place within the context of clinical trial participation, which is an additional novelty. Research teams must develop informational materials to help participants understand the clinical trial and input from local research staff and community members can improve the content and format of these materials.MethodsThis paper discusses the development of illustrated materials developed for microbicide trial participants, presenting examples from two studies. In both studies, research staff and community advisory groups collaborated to review and revise materials.ResultsCollaborative efforts revealed insights about how to convey information about clinical trial participation and microbicide use. These insights highlighted realities of the local context, details that might be misunderstood, illustrations of a sensitive nature and concerns about blood testing. In particular, information about blood testing and product use instructions required careful consideration. Although the research team anticipated needing advice on how best to convey information on these topics to participants, some aspects of potential participant concerns about these topics were also new to the research team. Community advisors and local research staff suggested better ways to convey this information, and provided guidance on how to use the materials.ConclusionsThe collaboration served to develop informational materials for microbicide trial participants. Furthermore, staff gained a better understanding of issues and concerns that could influence trial participation. A collaborative engagement process can provide important insights into local culture and knowledge beyond what is needed for development of clinical trial participant information materials. Research teams should be sensitive to this possibility, avail themselves of information and take appropriate action.

Communicating about microbicides with women in mind: tailoring messages for specific audiences

IntroductionCurrent HIV prevention options are unrealistic for most women; however, HIV prevention research has made important strides, including on-going development of antiretroviral-based vaginal microbicide gels. Nevertheless, social-behavioural research suggests that women's ability to access and use new HIV prevention technologies will be strongly influenced by a range of socio-cultural, gender and structural factors which should be addressed by communications and marketing strategies, so that these products can be positioned in ways that women can use them.MethodsBased on an extensive literature review and in-country policy consultation, consisting of approximately 43 stakeholders, we describe barriers and facilitators to HIV prevention, including potential microbicide use, for four priority audiences of Kenyan women (female sex workers [FSWs], women in stable and discordant relationships, and sexually active single young women). We then describe how messages that position microbicides might be tailored for each audience of women.ResultsWe reviewed 103 peer-reviewed articles and reports. In Kenya, structural factors and gender inequality greatly influence HIV prevention for women. HIV risk perception and the ability to consistently use condoms and other prevention products often vary by partner type. Women in stable relationships find condom use challenging because they connote a lack of trust. However, women in other contexts are often able to negotiate condom use, though they may face challenges with consistent use. These women include FSWs who regularly use condoms with their casual clients, young women in the initial stages of a sexual relationship and discordant couples. Thus, we consider two approaches to framing messages aimed at increasing general awareness of microbicides – messages that focus strictly on HIV prevention and ones that focus on other benefits of microbicides such as increased pleasure, intimacy or sexual empowerment, in addition to HIV prevention.ConclusionsIf carefully tailored, microbicide communication materials may facilitate product use by women who do not currently use any HIV prevention method. Conversely, message tailoring for women with high-risk perception will help ensure that microbicides are used as additional protection, together with condoms.

Attitudes towards microbicide use for bacterial vaginosis in pregnancy

Background Bacterial vaginosis (BV) is the most common reproductive tract infection (RTI) and is a significant risk factor for preterm birth. Microbicides could be an option for the prevention and treatment of BV in pregnancy, and understanding use of the product will be crucial. The present study explored attitudes of women in the third trimester of pregnancy regarding topical microbicide use for the prevention and treatment of BV. Twenty-six women in their third trimester were interviewed regarding their knowledge and beliefs about RTIs during pregnancy and attitudes concerning the use of topical microbicides for prevention and treatment of BV. Participants had a mean age of 24.9 years, were largely under-represented minorities and the majority had had past pregnancies. Participants had knowledge and experience with RTIs but not BV. They were open to the use of microbicides for prevention or treatment of BV, but believed that women requiring treatment would be more motivated. Rationales for acceptability were most commonly related to the baby's health. Practical issues that may interfere with use were often, but not always, related to pregnancy. There was a range of attitudes about partner involvement in decision-making and the practicalities of product use. Pregnant women are knowledgeable about RTIs but not necessarily BV. The women in this study found microbicide use acceptable, particularly for treatment. To improve acceptability and use, education would be needed about BV and possible complications, how to overcome practical problems and the value of involving partners in the decision.

The Implications of Post-coital Intravaginal Cleansing for the Introduction of Vaginal Microbicides in South Africa

Post-coital intravaginal cleansing (IVC) could counteract the protective effect of a vaginal microbicide. IVC less than 1 h after sex is discouraged in most microbicide trials. During a microbicide trial in KwaZulu-Natal, we collected quantitative data on post-coital IVC. We discussed IVC during in-depth-interviews (IDIs) and focus-group discussions (FGDs) with women enrolled in the trial, and during FGDs with community members. Nearly one-third (336/1,143) of women reported IVC less than an hour after sex. In multivariate analysis, post-coital IVC was associated with younger age, larger household size, greater sexual activity, consistent gel use, and clinic of enrolment. During IDIs and FGDs, respondents described post-coital IVC as a common hygiene practice motivated by the need to remove semen, vaginal fluids and sweat, although this practice may be amenable to change in the context of microbicide use. We need to consider strategies for influencing post-coital IVC practices in future microbicide trials and delivery programmes.

Adolescents’ and Young Women’s Use of a Microbicide Surrogate Product When Receiving Oral Sex

Study ObjectiveGenital herpes, which can be spread through oral sex, is an important target for microbicides. We examined episode-specific predictors of young women’s receptive oral sex and of microbicide surrogate use. DesignLongitudinal study. SettingParticipants were recruited to participate in a microbicide acceptability study from adolescent clinics and local colleges and through snowballing. ParticipantsYoung women (ages 14 to 21 y) who reported sexual contact on at least 1 weekly phone interview (n = 181) were included from the larger sample of 208 young women. Main Outcome MeasuresOn weekly diary phone interviews, participants reported whether or not their last sexual contact included receptive oral sex and whether or not their last sexual contact included use of a microbicide surrogate. Results and ConclusionsParticipants reported a total of 1042 episodes of sexual contact of which 311 included receptive oral sex and 354 included microbicide surrogate use. Being older, having sex for the first time with a partner, and having given oral sex were associated with having received oral sex during a sexual episode. Being older, being African American, and having discussed the microbicide surrogate with their partner were associated with having used the microbicide surrogate use during a sexual episode. These results indicate that oral sex should be considered in the design of clinical trials. Future studies need to evaluate ways to promote consistent microbicide use in the context of receiving oral sex as well as those factors (eg, taste, pleasure) which may serve as a barrier.

Peptide-derivatized SB105-A10 dendrimer inhibits the infectivity of R5 and X4 HIV-1 strains in primary PBMCs and cervicovaginal histocultures.

Peptide dendrimers are a class of molecules that exhibit a large array of biological effects including antiviral activity. In this report, we analyzed the antiviral activity of the peptide-derivatized SB105-A10 dendrimer, which is a tetra-branched dendrimer synthetized on a lysine core, in activated peripheral blood mononuclear cells (PBMCs) that were challenged with reference and wild-type human immunodeficiency virus type 1 (HIV-1) strains. SB105-A10 inhibited infections by HIV-1 X4 and R5 strains, interfering with the early phases of the viral replication cycle. SB105-A10 targets heparan sulfate proteoglycans (HSPGs) and, importantly, the surface plasmon resonance (SPR) assay revealed that SB105-A10 strongly binds gp41 and gp120, most likely preventing HIV-1 attachment/entry through multiple mechanisms. Interestingly, the antiviral activity of SB105-A10 was also detectable in an organ-like structure of human cervicovaginal tissue, in which SB105-A10 inhibited the HIV-1ada R5 strain infection without altering the tissue viability. These results demonstrated the strong antiviral activity of SB105-A10 and suggest a potential microbicide use of this dendrimer to prevent the heterosexual transmission of HIV-1.

Clinical use of vaginal or rectally applied microbicides in patients suffering from HIV/AIDS

Microbicides, primarily used as topical pre-exposure prophylaxis, have been proposed to prevent sexual transmission of HIV. This review covers the trends and challenges in the development of safe and effective microbicides to prevent sexual transmission of HIV Initial phases of microbicide development used such surfactants as nonoxynol-9 (N-9), C13G, and sodium lauryl sulfate, aiming to inactivate the virus. Clinical trials of microbicides based on N-9 and C31G failed to inhibit sexual transmission of HIV. On the contrary, N-9 enhanced susceptibility to sexual transmission of HIV-1. Subsequently, microbicides based on polyanions and a variety of other compounds that inhibit the binding, fusion, or entry of virus to the host cells were evaluated for their efficacy in different clinical setups. Most of these trials failed to show either safety or efficacy for prevention of HIV transmission. The next phase of microbicide development involved antiretroviral drugs. Microbicide in the form of 1% tenofovir vaginal gel when tested in a Phase IIb trial (CAPRISA 004) in a coitally dependent manner revealed that tenofovir gel users were 39% less likely to become HIV-infected compared to placebo control. However, in another trial (VOICE MTN 003), tenofovir gel used once daily in a coitally independent mode failed to show any efficacy to prevent HIV infection. Tenofovir gel is currently in a Phase III safety and efficacy trial in South Africa (FACTS 001) employing a coitally dependent dosing regimen. Further, long-acting microbicide-delivery systems (vaginal ring) for slow release of such antiretroviral drugs as dapivirine are also undergoing clinical trials. Discovering new markers as correlates of protective efficacy, novel long-acting delivery systems with improved adherence in the use of microbicides, discovering new compounds effective against a broad spectrum of HIV strains, developing multipurpose technologies incorporating additional features of efficacy against other sexually transmitted infections, and contraception will help in moving the field of microbicide development forward.

Young Women's Experience with Using Videoconferencing for the Assessment of Sexual Behavior and Microbicide Use

Videoconferencing (VC) systems are increasingly recognized as a viable means of enhancing communication across different geographic regions and have been used within multiple settings. Until now, despite increased use and diverse applications, VC has received relatively little attention as a data collection tool in qualitative research. The literature on preferred data collection methods for sensitive topics offers different perspectives, with no clear consensus on the best approach for collecting sensitive data. We sought to determine if VC is a feasible tool for eliciting sexual history from participants in a vaginal microbicide study. Fifty-nine young women who participated in a Phase 1 microbicide safety and acceptability study at three sites (Tampa, FL; Pittsburgh, PA; and San Juan, Puerto Rico) were interviewed through VC from New York City. During the third VC session, participants gave feedback on their experience using the method. Most of the participants reported that they preferred VC to phone-only interviews. Participants noted that because of the sensitive nature of the interviews, geographical distance from the interviewer facilitated disclosure. Despite some technical problems, such as the time delay in video transmission and occasional loss of connection, participants expressed a high degree of satisfaction with using VC. VC seems to be a feasible alternative form of conducting in-depth interviews on sensitive topics. VC enables data collection from geographically dispersed research participants without the cost and time burden of traveling to sites or developing local interviewer capabilities when the number of interviews is small.

Population-level benefits from providing effective HIV prevention means to pregnant women in high prevalence settings.

BackgroundHIV prevalence among pregnant women in Southern Africa is extremely high. Epidemiological studies suggest that pregnancy increases the risk of HIV sexual acquisition and that HIV infections acquired during pregnancy carry higher risk of mother-to-child transmission (MTCT). We analyze the potential benefits from extending the availability of effective microbicide to pregnant women (in addition to non-pregnant women) in a wide-scale intervention.Methods and FindingsA transmission dynamic model was designed to assess the impact of microbicide use in high HIV prevalence settings and to estimate proportions of new HIV infections, infections acquired during pregnancy, and MTCT prevented over 10 years. Our analysis suggests that consistent use of microbicide with 70% efficacy by 60% of non-pregnant women may prevent approximately 40% and 15% of new infections in women and men respectively over 10 years, assuming no additional increase in HIV risk to either partner during pregnancy (RRHIV/preg = 1). It may also prevent 8–15% MTCT depending on the increase in MTCT risk when HIV is acquired during pregnancy compared to before pregnancy (RRMTCT/preg). Extending the microbicides use during pregnancy may improve the effectiveness of the intervention by 10% (RRHIV/preg = 1) to 25% (RRHIV/preg = 2) and reduce the number of HIV infections acquired during pregnancy by 40% to 70% in different scenarios. It may add between 6% (RRHIV/preg = 1, RRMTCT/preg = 1) and 25% (RRHIV/preg = 2, RRMTCT/preg = 4) to the reduction in the residual MTCT.ConclusionProviding safe and effective microbicide to pregnant women in the context of wide-scale interventions would be desirable as it would increase the effectiveness of the intervention and significantly reduce the number of HIV infections acquired during pregnancy. The projected benefits from covering pregnant women by the HIV prevention programs is more substantial in communities in which the sexual risk during pregnancy is elevated.

The effect of cationic microbicide exposure againstBurkholderia cepaciacomplex (Bcc); the use ofBurkholderia latastrain 383 as a model bacterium

The extensive use of microbicides in a wide range of applications has been questioned with regard to their role in the development of bacterial resistance to antimicrobials. This study aims to measure the phenotypic and genotypic changes in Burkholderia lata strain 383 exposed to chlorhexidine gluconate (CHG) and benzalkonium chloride (BZC), two commonly used cationic microbicides. The susceptibility of B. lata strain 383 to CHG and BZC and a range of antibiotics was determined using standardized MIC, MBC and antibiotic susceptibility testing protocols before and after short-term exposure to a low microbicide concentration. Measurements were performed on four separate occasions over a 1-year period. Changes in gene expression were investigated using quantitative real-time PCR. Although the susceptibility profile to CHG and BZC was not altered, a change in antibiotic susceptibility profile was observed for ceftazidime, and for imipenem and ciprofloxacin in 2/4 repeats. An outer membrane protein and ABC transporter were found to be significantly upregulated following treatment with BZC and CHG, respectively. The comparison of MIC and MBC results following microbicide exposure with baseline data offered a prospective protocol to quantify any change in bacterial susceptibility profile. However, the use of a standardized antibiotic susceptibility protocol with B. lata strain 383 showed some inconsistencies in results between repeats. With ever-increasing interest in the impact of microbicides on emerging antimicrobial resistance in bacteria growing, this study demonstrated that comparing susceptibility profile obtained after exposure to microbicides with baseline susceptibility values could play a role in establishing the potential risk of microbicide resistance and cross-resistance development and also in the development of a protocol that allows the prediction of microbicide resistance.

No Evidence for Selection of HIV-1 with Enhanced Gag-Protease or Nef Function among Breakthrough Infections in the CAPRISA 004 Tenofovir Microbicide Trial

BackgroundUse of antiretroviral-based microbicides for HIV-1 prophylaxis could introduce a transmission barrier that inadvertently facilitates the selection of fitter viral variants among incident infections. To investigate this, we assessed the in vitro function of gag-protease and nef sequences from participants who acquired HIV-1 during the CAPRISA 004 1% tenofovir microbicide gel trial.Methods and ResultsWe isolated the earliest available gag-protease and nef gene sequences from 83 individuals and examined their in vitro function using recombinant viral replication capacity assays and surface protein downregulation assays, respectively. No major phylogenetic clustering and no significant differences in gag-protease or nef function were observed in participants who received tenofovir gel versus placebo gel prophylaxis.ConclusionResults indicate that the partial protective effects of 1% tenofovir gel use in the CAPRISA 004 trial were not offset by selection of transmitted/early HIV-1 variants with enhanced Gag-Protease or Nef fitness.

P3.362 Microbicide Use During Pregnancy: Acceptability For Prevention/Treatment and the Role of Partners

ObjectivesTo explore pregnant women’s acceptance of microbicides for reproductive tract infections (RTIs).MethodsTo date, we have analysed interview transcripts of 15 women in their third trimester who participated in a qualitative...

P1.037 Analysis of the Major Human Cervical Mucus Patterns in Normal Healthy Females Using Different Methods of Birth Control

BackgroundMucins and glycoproteins in the cervicovaginal environment are an important component of female genital tract (FGT) innate immunity. Optimally, microbicide use should not disrupt the mucus layer protecting the genital...

Topical Microbicides—What's New?

Topical microbicides are an important, promising but complex HIV prevention technology under development. After 11 disappointing effectiveness trial outcomes of 6 candidate products (some tested as multiple doses and formulations) over the past 20 years, there is renewed optimism that a safe and effective microbicide will soon be available if the recent success of coitally linked use of the antiretroviral-based microbicide, 1% tenofovir gel, is confirmed. Studies of new antiviral agents, novel delivery mechanisms, and combination/multipurpose products that address challenges of adherence, enhance the effectiveness of tenofovir gel, and address sexual and reproductive health needs of men and women, including preventing HIV infection, are already underway.

Does Microbicide Use in Consumer Products Promote Antimicrobial Resistance? A Critical Review and Recommendations for a Cohesive Approach to Risk Assessment

The increasing use of microbicides in consumer products is raising concerns related to enhanced microbicide resistance in bacteria and potential cross resistance to antibiotics. The recently published documents on this topic from the European Commission have spawned much interest to better understand the true extent of the putative links for the benefit of the manufacturers, regulators, and consumers alike. This white paper is based on a 2-day workshop (SEAC-Unilever, Bedford, United Kingdom; June 2012) in the fields of microbicide usage and resistance. It identifies gaps in our knowledge and also makes specific recommendations for harmonization of key terms and refinement/standardization of methods for testing microbicide resistance to better assess the impact and possible links with cross resistance to antibiotics. It also calls for a better cohesion in research in this field. Such information is crucial to developing any risk assessment framework on microbicide use notably in consumer products. The article also identifies key research questions where there are inadequate data, which, if addressed, could promote improved knowledge and understanding to assess any related risks for consumer and environmental safety.

Inhibition of infection and transmission of HIV-1 and lack of significant impact on the vaginal commensal lactobacilli by carbohydrate-binding agents

A selection of carbohydrate-binding agents (CBAs) with different glycan specificities were evaluated for their inhibitory effect against HIV infection and transmission, and their interaction with vaginal commensal bacteria. Several assays were used for the antiviral evaluation: (i) cell-free virus infection of human CD4+ T lymphocyte C8166 cells; (ii) syncytium formation in co-cultures of persistently HIV-1-infected HUT-78/HIV-1 and non-infected CD4+ SupT1 cells; (iii) DC-SIGN-directed capture of HIV-1 particles; and (iv) transmission of DC-SIGN-captured HIV-1 particles to uninfected CD4+ C8166 cells. CBAs were also examined for their interaction with vaginal commensal lactobacilli using several viability, proliferation and adhesion assays. The CBAs showed efficient inhibitory activity in the nanomolar to low-micromolar range against four events that play a crucial role in HIV-1 infection and transmission: cell-free virus infection, fusion between HIV-1-infected and non-infected cells, HIV-1 capture by DC-SIGN and transmission of DC-SIGN-captured virus to T cells. As candidate microbicides should not interfere with the normal human microbiota, we examined the effect of CBAs against Lactobacillus strains, including a variety of vaginal strains, a gastrointestinal strain and several non-human isolates. None of the CBAs included in our studies inhibited the growth of these bacteria in several media, affected their viability or had any significant impact on their adhesion to HeLa cell monolayers. The CBAs in this study were inhibitory to HIV-1 in several in vitro infection and transmission models, and may therefore qualify as potential microbicide candidates. The lack of significant impact on commensal vaginal lactobacilli is an important property of these CBAs in view of their potential microbicidal use.