Microbicide Studies Research Articles

Sexual behaviour, changes in sexual behaviour and associated factors among women at high risk of HIV participating in feasibility studies for prevention trials in Tanzania.

Risk reduction towards safer behaviour is promoted after enrolment in HIV prevention trials. We evaluated sexual behaviour, changes in sexual behaviour and factors associated with risky behaviour after one-year of follow-up among women enrolled in HIV prevention trials in Northern Tanzania. Self-reported information from 1378 HIV-negative women aged 18-44 enrolled in microbicide and vaccine feasibility studies between 2008-2010,was used to assess changes in behaviour during a 12-month follow-up period. Logistic regression with random intercepts was used to estimate odds ratios for trends in each behaviour over time. A behavioural risk score was derived from coefficients of three behavioural variables in a Poisson regression model for HIV incidence and thereafter, dichotomized to risky vs less-risky behaviour. Logistic regression was then used to identify factors associated with risky behaviour at 12 months. At baseline, 22% reported multiple partners, 28% were involved in transactional sex and only 22% consistently used condoms with non-regular partners. The proportion of women reporting multiple partners, transactional sex and high-risk sex practices reduced at each 3-monthly visit (33%, 43% and 47% reduction in odds per visit respectively, p for linear trend <0.001 for all), however, there was no evidence of a change in the proportion of women consistently using condoms with non-regular partners (p = 0.22). Having riskier behaviours at baseline, being younger than 16 years at sexual debut, having multiple partners, selling sex and excessive alcohol intake at baseline were strongly associated with increased odds of risky sexual behaviour after 12 months (p<0.005 for all). An overall reduction in risky behaviours over time was observed in HIV prevention cohorts. Risk reduction counselling was associated with decreased risk behaviour but was insufficient to change behaviours of all those at highest risk. Biological HIV prevention interventions such as PrEP for individuals at highest risk, should complement risk reduction counselling so as to minimize HIV acquisition risk.

Vaginal progesterone to prevent preterm delivery among HIV-infected pregnant women in Zambia: A feasibility study.

Antenatal vaginal progesterone (VP) reduces the risk of preterm birth (PTB) in women with shortened cervical length, and we hypothesize that it may also prevent PTB in women with HIV as their primary risk factor. We conducted a pilot feasibility study in Lusaka, Zambia to investigate uptake, adherence, and retention in preparation for a future efficacy trial. This was a double-masked, placebo-controlled, randomized trial of 200mg daily self-administered VP suppository or placebo. Pregnant women with HIV who were initiating or continuing antiretroviral therapy were eligible for participation. Potential participants underwent ultrasound to assess eligibility; we excluded those ≥24 gestational weeks, with non-viable, multiple gestation, or extrauterine pregnancies, with short cervix (<2.0cm), or with prior spontaneous PTB. Participants initiated study product between 20–24 weeks of gestation and continued to 37 weeks (or delivery, if sooner). The primary outcome was adherence (proportion achieving ≥80% study product use), assessed by dye stain assay of returned single-use vaginal applicators. Secondary outcomes with pre-defined feasibility targets were: uptake (≥50% eligible participants enrolled) and retention (≥90% ascertainment of delivery outcomes). We also evaluated preliminary efficacy by comparing the risk of spontaneous PTB <37 weeks between groups. From July 2017 to June 2018, 208 HIV-infected pregnant women were eligible for screening and 140 (uptake = 67%) were randomly allocated to VP (n = 70) or placebo (n = 70). Mean adherence was 94% (SD±9.4); 91% (n = 125/137) achieved overall adherence ≥80%. Delivery outcomes were ascertained from 134 (96%) participants. Spontaneous PTB occurred in 10 participants (15%) receiving placebo and 8 (12%) receiving progesterone (RR 0.82; 95%CI:0.34–1.97). Spontaneous PTB < 34 weeks occurred in 6 (9%) receiving placebo and 4 (6%) receiving progesterone (RR 0.67; 95%CI:0.20–2.67). In contrast to findings from vaginal microbicide studies in HIV-uninfected, non-pregnant women, our trial participants were highly adherent to daily self-administered vaginal progesterone. The study’s a priori criteria for uptake, adherence, and retention were met, indicating that a phase III efficacy trial would be feasible.

Social harms in female-initiated HIV prevention method research: state of the evidence.

Assessment of safety is an integral part of real-time monitoring in clinical trials. In HIV prevention research, safety of investigational products and trial participation has been expanded to include monitoring for 'social harms', generally defined as negative consequences of trial participation that may manifest in social, psychological, or physical ways. Further research on social harms within HIV prevention research is needed to understand the potential safety risks for women and advance the implementation of prevention methods in real-world contexts. Secondary analysis of quantitative data from three randomized, double-blind, placebo-controlled trials of microbicide candidates in sub-Saharan Africa was conducted. Additionally, we assessed data from two prospective cohort studies that included participants who became HIV-positive or pregnant during parent trials. Social harms reporting was low across the largest and most recent microbicide studies. Social harm incidence per 100 person-years ranged from 1.10 (95% CI 0.78-1.52) to 3.25 (95% CI 2.83-3.74) in the phased trials. Reporting differed by dosing mechanism (e.g. vaginal gel, oral tablet, ring) and study, most likely as a function of measurement differences. Social harms were most frequently associated with male partners, rather than, for example, experiences of stigma in the community. Measurement and screening for social harms is an important component of conducting ethical research of novel HIV prevention methods. To date, social harm incidence reported in microbicide trials has been relatively low (<4% per 100 person-years), and the majority have been partner-related events. However, any incidence of social harm within the context of HIV prevention is important to capture and understand for the safety of individuals, and for the successful impact of prevention methods in a real-world context.

The relationship between vaginal ring use and intimate partner violence and social harms: formative research outcomes from the CHARISMA study in Johannesburg, South Africa

ABSTRACTDespite being designed for autonomous use, research suggests partner approval is often in women's microbicide use. Microbicide study participants have described many ways product use affects relationships, from improving sexual pleasure to increasing harm, including exacerbating intimate partner violence (IPV). As the dapivirine ring proceeds closer to licensure, supporting women's agency to use microbicides safely is a priority. We conducted 42 in-depth interviews with former participants of the Microbicide Trials Network (MTN)-020 trial of the dapivirine vaginal ring and their male partners in Johannesburg, South Africa, to explore how ring use and partnership dynamics interacted. We sampled women who reported harms or partner non-support and women with supportive partners. Male and female narratives revealed high background levels of IPV. Women described how study participation/ring use exacerbated violence, and for a few couples served as a rationale for additional abuse. In response, women described feeling powerless and fearful of conflict, resulting in product nonuse. For one participant violence was reduced, and for several others, empowerment was sparked. These findings suggest future providers have the opportunity to shift more women from a place of fear/violence to one of safety/empowerment through the integration of IPV screening and relationship counselling.

Coordination versatility of N2O4 polydentate hydrazonic ligand in Zn(II), Cu(II), Ni(II), Co(II), Mn(II) and Pd(II) complexes and antimicrobial evaluation

New polydentate hydrazone ligand, was synthesized by the condensation of 1,5-dimethyl-3-oxo-2-phenylpyrazole-4-carbaldehyde with adipodihydrazide. The structure of the synthesized ligand, N′1,N′6-bis((1,5-dimethyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazol-4-yl) methylene) adipohydrazide was elucidated by various analytical and spectroscopic techniques. The reactions of the ligand with zinc(II), copper(II), nickel(II), cobalt(II), manganese(II) and palladium(II) salts afforded homobinuclear metal complexes. Characterization and structure elucidation of the prepared complexes were achieved using different analytical and spectroscopic techniques. The analyses data indicated that this ligand behaved as N2O4 dibasic hexadentate ligand bonded covalency to the metal ions through the enolic carbonyl oxygen of hydrazide moiety and coordinated via carbonyl oxygen of antipyrine moiety and azomethine nitrogen atoms forming distorted octahedral geometry around the metal ions. The ESR spectra of copper(II) complexes (3) and (4) showed an axial symmetry with g||>g⊥>ge, indicating distorted octahedral structure and presence of the unpaired electron in d(x2−y2) orbital. The microbicide studies of the ligand and its metal complexes (2), (3), (4), (5), (8), (11) and (13) showed that, all these complexes exhibit moderate to mild inhibitory effects on B. subtilis, E. coli while complexes (2), (3), (4) and (13) exhibit moderate to mild inhibitory effects on A. niger.

Characteristics of HIV target CD4 T cells collected using different sampling methods from the genital tract of HIV seronegative women.

BackgroundUnderstanding the immune profile of CD4 T cells, the primary targets for HIV, in the female genital tract (FGT) is critical for evaluating and developing effective biomedical HIV prevention strategies in women. However, longitudinal investigation of HIV susceptibility markers expressed by FGT CD4 T cells has been hindered by low cellular yield and risk of sampling-associated trauma. We investigated three minimally invasive FGT sampling methods to characterize and compare CD4 T cell yield and phenotype with the goal of establishing feasible sampling strategies for immune profiling of mucosal CD4 T cells.Methods and resultsFGT samples were collected bimonthly from 12 healthy HIV negative women of reproductive age in the following order: 1) Cervicovaginal lavage (CVL), 2) two sequential endocervical flocked swabs (FS), and 3) two sequential endocervical cytobrushes (CB1, CB2). Cells were isolated and phentoyped via flow cytometry. CD4 T cell recovery was highest from each individual CB compared to either CVL or FS (p < 0.0001). The majority of CD4 T cells within the FGT, regardless of sampling method, expressed CCR5 relative to peripheral blood (p < 0.01). Within the CB, CCR5+ CD4 T cells expressed significantly higher levels of α4β7, CD69, and low levels of CD27 relative to CCR5- CD4 T cells (all p < 0.001). We also identified CD4 Treg lineage cells expressing CCR5 among CB samples.ConclusionsUsing three different mucosal sampling methods collected longitudinally we demonstrate that CD4 T cells within the FGT express CCR5 and α4β7 and are highly activated, attributes which could act in concert to facilitate HIV acquisition. FS and CB sampling methods can allow for investigation of strategies to reduce HIV target cells in the FGT and could inform the design and interpretation microbicide and vaccine studies in women.

Parents’ and Adolescents’ Attitudes about Parental Involvement in Clinical Research

Study ObjectiveTo understand parent and adolescent attitudes toward parental involvement during clinical trials and factors related to those attitudes. DesignAs part of a study on willingness to participate in a hypothetical microbicide study, adolescents and their parents were interviewed separately. SettingAdolescent medicine clinics in New York City. ParticipantsThere were 301 dyads of adolescents (ages 14-17 years; 62% female; 72% Hispanic) and their parents. InterventionsNone. Main Outcome MeasuresThe interview included questions on demographic characteristics, sexual history, and family environment (subscales of the Family Environment Scale) that were associated with attitudes about parental involvement. ResultsFactor analysis of the parental involvement scale yielded 2 factors: LEARN, reflecting gaining knowledge about study test results and behaviors (4 items) and PROCEDURE, reflecting enrollment and permissions (4 items). Adolescents endorsed significantly fewer items on the LEARN scale and the PROCEDURE scale indicating that adolescents believed in less parental involvement. There was no significant concordance between adolescents and their own parents on the LEARN scale and the PROCEDURE scale. In final multivariate models predicting attitudes, adolescents who were female and had sexual contact beyond kissing, and non-Hispanic parents had lower LEARN scores. Adolescents who were older, had previous research experience, and reported less moral or religious emphasis in their family had lower PROCEDURE scores; there were no significant predictors for parents in the multivariate analyses. ConclusionParents wanted greater involvement in the research process than adolescents. Recruitment and retention might be enhanced by managing these differing expectations.

Optimizing HIV prevention for women: a review of evidence from microbicide studies and considerations for gender-sensitive microbicide introduction.

IntroductionMicrobicides 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.MethodsWe 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 discussionThe 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.ConclusionsIdentifying 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.

Motivating, Measuring and Monitoring Adherence in the FACTS 001 Tenofovir Gel Microbicide Study

Motivating, Measuring and Monitoring Adherence in the FACTS 001 Tenofovir Gel Microbicide Study

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.

To What did They Consent? Understanding Consent Among Low Literacy Participants in a Microbicide Feasibility Study in Mazabuka, Zambia.

We conducted a study to review the consenting process in a vaginal microbicide feasibility study conducted in Mazabuka, Zambia. Participants were drawn from those participating in the microbicide study. A questionnaire and focus group discussion were used to collect information on participants' understanding of study aims, risks and benefits. Altogether, 200 participants took part in this study. The results of the study showed that while all participants signed or endorsed their thumbprints to the consent forms, full informed consent was not attained from most of the participants since 77% (n = 154) of the participants had numerous questions about the study and 34% (n = 68) did not know who to get in touch with concerning the study. Study objectives were not fully understood by over 61% of the participants. Sixty four percent of the participants were not sure of the risks of taking part in the microbicide study. A significant number thought the study was all about determining their HIV status. Some participants were concerned that their partners were not on the trial as they were convinced that being on the study meant that that they had a lifetime protection from HIV infection. The process of obtaining consent was inadequate as various phases of the study were not fully understood. We recommend the need for researchers to reinforce the consenting process in all studies and more so when studies are conducted in low literacy populations.

Unbiased Proteomics Analysis Demonstrates Significant Variability in Mucosal Immune Factor Expression Depending on the Site and Method of Collection

Female genital tract secretions are commonly sampled by lavage of the ectocervix and vaginal vault or via a sponge inserted into the endocervix for evaluating inflammation status and immune factors critical for HIV microbicide and vaccine studies. This study uses a proteomics approach to comprehensively compare the efficacy of these methods, which sample from different compartments of the female genital tract, for the collection of immune factors. Matching sponge and lavage samples were collected from 10 healthy women and were analyzed by tandem mass spectrometry. Data was analyzed by a combination of differential protein expression analysis, hierarchical clustering and pathway analysis. Of the 385 proteins identified, endocervical sponge samples collected nearly twice as many unique proteins as cervicovaginal lavage (111 vs. 61) with 55% of proteins common to both (213). Each method/site identified 73 unique proteins that have roles in host immunity according to their gene ontology. Sponge samples enriched for specific inflammation pathways including acute phase response proteins (p = 3.37×10−24) and LXR/RXR immune activation pathways (p = 8.82×10−22) while the role IL-17A in psoriasis pathway (p = 5.98×10−4) and the complement system pathway (p = 3.91×10−3) were enriched in lavage samples. Many host defense factors were differentially enriched (p<0.05) between sites including known/potential antimicrobial factors (n = 21), S100 proteins (n = 9), and immune regulatory factors such as serpins (n = 7). Immunoglobulins (n = 6) were collected at comparable levels in abundance in each site although 25% of those identified were unique to sponge samples. This study demonstrates significant differences in types and quantities of immune factors and inflammation pathways collected by each sampling technique. Therefore, clinical studies that measure mucosal immune activation or factors assessing HIV transmission should utilize both collection methods to obtain the greatest representation of immune factors secreted into the female genital tract.

Effects of Partnership Change on Microbicide Gel Adherence in a Clinical Trial (HPTN 035)

Use of HIV prevention methods may vary for women by types of sexual partners. In a microbicide safety and effectiveness trial (HPTN 035) differences in adherence to a microbicide study gel were compared between women with new versus ongoing partnerships over time. 1,757 women in the three HPTN 035 trial's arms completed the Follow-up Partner Status (FPS) questionnaire at their last study visit. Women married at baseline were asked if they had the same husband, new husband or new partner. Unmarried women were asked if they had changed partners or married. Self-reported gel adherence during the last sex act was compared at each quarterly visit between women with ongoing versus new partners. High gel adherence was compared with low gel adherence (85-100 vs. <85 % of last vaginal sex acts reported with gel use, respectively) in multivariable models to assess associations with partner change. Overall 7 % of women (n = 123) reported a new partner and 41 % (51) of those reported a new husband. Median gel adherence was reported to be 100 % in women with ongoing partners and 75 % for women with new partners (p < 0.001). In women reporting no gel use in their last sex act, only 12.5 % of the women with a new partner and none of those with an ongoing partner reported using condoms (p < 0.001). Fewer women with new partners reported using both the gel and condom during the last sex act as compared to women with ongoing partners (median 50 vs. 71.4 %, p < 0.001). After adjusting for age, site, education level, and sexual frequency, women with ongoing partners were more likely to report high gel adherence than those with new partners (AOR 2.5, 95 % CI 1.6, 3.9). This pattern persisted when gel use over time was compared between women with new versus ongoing partners. In the HPTN 035 trial, women with new partners had higher HIV incidence and reported less gel use and higher condom use. Specific counseling and support are needed to help women use potential HIV prevention methods, including microbicides, when they are changing partners.

Safety and Tolerability of Tenofovir for Preexposure Prophylaxis Among Men Who Have Sex With Men

Safety and Tolerability of Tenofovir for Preexposure Prophylaxis Among Men Who Have Sex With Men

The epidemiology of HIV and HSV-2 infections among women participating in microbicide and vaccine feasibility studies in Northern Tanzania.

ObjectivesTo prepare for future HIV prevention trials, we conducted prospective cohort studies among women working in food and recreational facilities in northern Tanzania. We examined the prevalence and incidence of HIV and HSV-2, and associated risk factors.MethodsWomen aged 18–44 years working in food and recreational facilities were screened to determine their eligibility for the studies. Between 2008–2010, HIV-negative women were enrolled and followed for 12 months. At enrolment and 3-monthly, we collected socio-demographic and behavioural data, and performed clinical examinations for collection of biological specimens that were tested for reproductive tract infections. Risk factors for HIV and HSV-2 incidence were investigated using Poisson regression models.ResultsWe screened 2,229 and enrolled 1,378 women. The median age was 27 years (interquartile range, IQR 22, 33), and median duration working at current facility was 2 years. The prevalences of HIV at screening and HSV-2 at enrolment were 16% and 67%, respectively. Attendance at the 12-month visit was 86%. HIV and HSV-2 incidence rates were 3.7 (95% confidence interval, CI: 2.8,5.1) and 28.6 (95% CI: 23.5,35.0)/100 person-years, respectively. Women who were separated, divorced, or widowed were at increased risk of HIV (adjusted incidence rate ratio, aRR = 6.63; 95% CI: 1.97,22.2) and HSV-2 (aRR = 2.00; 95% CI: 1.15,3.47) compared with married women. Women reporting ≥3 partners in the past 3 months were at higher HIV risk compared with women with 0–1 partner (aRR = 4.75; 95% CI: 2.10,10.8), while those who had reached secondary education or above were at lower risk of HSV-2 compared with women with incomplete primary education (aRR = 0.42; 95% CI: 0.22,0.82).ConclusionsHIV and HSV-2 rates remain substantially higher in this cohort than in the general population, indicating urgent need for effective interventions. These studies demonstrate the feasibility of conducting trials to test new interventions in this highly-mobile population.

P3.361 Male Involvement in the Voice Microbicide Trial at Kampala Site Uganda - a Worthwhile Venture

BackgroundMakerere University-Johns Hopkins University research collaboration (MU-JHU) conducted a VOICE study which was a phase 2B safety and effectiveness study of Tenofovir 1% gel, Tenofovir tablet and Truvada tablet for...

Animal models for microbicide safety and efficacy testing

Early studies have cast doubt on the utility of animal models for predicting success or failure of HIV-prevention strategies, but results of multiple human phase 3 microbicide trials, and interrogations into the discrepancies between human and animal model trials, indicate that animal models were, and are, predictive of safety and efficacy of microbicide candidates. Recent studies have shown that topically applied vaginal gels, and oral prophylaxis using single or combination antiretrovirals are indeed effective in preventing sexual HIV transmission in humans, and all of these successes were predicted in animal models. Further, prior discrepancies between animal and human results are finally being deciphered as inadequacies in study design in the model, or quite often, noncompliance in human trials, the latter being increasingly recognized as a major problem in human microbicide trials. Successful microbicide studies in humans have validated results in animal models, and several ongoing studies are further investigating questions of tissue distribution, duration of efficacy, and continued safety with repeated application of these, and other promising microbicide candidates in both murine and nonhuman primate models. Now that we finally have positive correlations with prevention strategies and protection from HIV transmission, we can retrospectively validate animal models for their ability to predict these results, and more importantly, prospectively use these models to select and advance even safer, more effective, and importantly, more durable microbicide candidates into human trials.

Rectal microbicide development.

The last few years have seen important progress in demonstrating the efficacy of oral pre-exposure prophylaxis, vaginal microbicides, and treatment as prevention as effective strategies for reducing the risk of acquiring or transmitting HIV infection. There has also been significant progress in the development of rectal microbicides. Preclinical non-human primate studies have demonstrated that antiretroviral microbicides can provide significant protection from rectal challenge with SIV or SHIV. Recent Phase 1 rectal microbicide studies have characterized the safety, acceptability, compartmental pharmacokinetics (PK), and pharmacodynamics (PD) of both UC781 and tenofovir gels. The tenofovir gel formulation used in vaginal studies was not well tolerated in the rectum and newer rectal-specific formulations have been developed and evaluated in Phase 1 studies. The PK/PD data generated in these Phase 1 studies may reduce the risk of advancing ineffective candidate rectal microbicides into late stage development. Tenofovir gel is currently poised to move into Phase 2 evaluation and it is possible that a Phase 2B/3 effectiveness study with this product could be initiated in the next 2-3 years.

Rectal microbicide development.

Individuals practicing unprotected receptive anal intercourse are at particularly high risk of HIV infection. Men who have sex with men (MSM) in the developed and developing world continue to have disproportionate and increasing levels of HIV infection. The past few years have seen important progress in demonstrating the efficacy of oral pre-exposure prophylaxis (PrEP), vaginal microbicides, and treatment as prevention, but there has also been significant progress in the development of rectal microbicides. The purpose of this review is to summarize the status of rectal microbicide research and to identify opportunities, challenges, and future directions in this important field of HIV prevention. Recent phase 1 rectal microbicide studies have characterized the safety, acceptability, compartmental pharmacokinetics, and pharmacodynamics of both UC781 and tenofovir gels. The tenofovir gel formulation used in vaginal studies was not well tolerated in the rectum and newer rectal-specific formulations have been developed and evaluated in phase 1 studies. Complex phase 1 studies have provided important data on candidate rectal microbicides. Tenofovir gel is poised to move into phase 2 evaluation and it is possible that a phase 2B/3 effectiveness study could be initiated in the next 2-3 years.

Rational design of HIV vaccines and microbicides: report of the EUROPRISE annual conference 2011

Europrise is a Network of Excellence supported by the European Commission within the 6th Framework programme from 2007 to 2012. The Network has involved over 50 institutions from 13 European countries together with 3 industrial partners and 6 African countries. The Network encompasses an integrated program of research, training, dissemination and advocacy within the field of HIV vaccines and microbicides. A central and timely theme of the Network is the development of the unique concept of co-usage of vaccines and microbicides. Training of PhD students has been a major task, and some of these post-graduate students have here summarized novel ideas emanating from presentations at the last annual Europrise meeting in Prague. The latest data and ideas concerning HIV vaccine and microbicide studies are included in this review; these studies are so recent that the majority have yet to be published. Data were presented and discussed concerning novel immunisation strategies; microbicides and PrEP (alone and in combination with vaccines); mucosal transmission of HIV/SIV; mucosal vaccination; novel adjuvants; neutralizing antibodies; innate immune responses; HIV/SIV pathogenesis and disease progression; new methods and reagents. These – necessarily overlapping topics - are comprehensively summarised by the Europrise students in the context of other recent exciting data.