Search

: Introduction: Adherence to HIV prevention methods is a challenge, particularly for young women in Sub?Saharan Africa. End?user research during product development can inform modifiable factors to increase future uptake and adherence. Methods: Preferences for four vaginally inserted placebo HIV prevention methods were assessed among Zimbabwean and South African young women using a crossover clinical design. For each of months 1 to 4, participants were asked to use a pre?coitally inserted film, insert (vaginal tablet) and gel once/week for a month, and a monthly ring in a randomly assigned sequence. Participants subsequently chose one preferred product to use as directed for the final study month. Women ranked the four products from most preferred to least preferred at enrolment and after trying all products. Results: A total of 200 women aged 18 to 30 (mean 23) were enrolled; 178 (89%) completed follow?up. At baseline, 41% of participants selected the gel as their most preferred product and 61% selected the ring as least preferred. During the crossover period, most (82% to 85%) self?reported using each product at least once a week, although only half the time with sex. Objective biomarker data confirmed adequate use of all products. After trying each product, rankings changed with the film, ring, insert and gel being selected by 29%, 28%, 26% and 16% respectively. Choice varied significantly by country (p < 0.001): More Zimbabweans chose the film (45%), and more South Africans chose the insert (34%). Among women choosing the ring, 88% reported using it every time with sex. By contrast, self?reported adherence was lower for ?on?demand? (coitally associated) products, with 40% to 55% using them every time during sex (p < 0.001). Conclusions: Preferences for these four dosage forms varied before and after use, and both within and across countries ? there was no clear favourite ? indicating the need for a range of options for end?users. The ring's popularity increased the most with use, was the second most preferred delivery system, and per self?report, provided more coverage during sex. These end?user perspectives provide important information to product developers and funding agencies., Introduction Adolescents and young women in Africa are at disproportionately high risk for HIV acquisition and the identification and delivery of safe, effective female?initiated prevention interventions is a public health [...]

The increase of proinflammatory cytokines in vaginal secretions may serve as a surrogate marker of unwanted inflammatory reaction to microbicide products topically applied for the prevention of sexually transmitted diseases, including HIV-1. Interleukin (IL)-l[beta] and IL-6 have been proposed as indicators of inflammation and increased risk of HIV-1 transmission; however, the lack of information regarding detection platforms optimal for vaginal fluids and interlaboratory variation limit their use for microbicide evaluation and other clinical applications. This study examines fluid matrix variants relevant to vaginal sampling techniques and proposes a model for interlaboratory comparisons across current cytokine detection technologies. II-1[beta] and IL-6 standards were measured by 12 laboratories in four countries, using 14 immunoassays and four detection platforms based on absorbance, chemiluminescence, electrochemiluminescence, and fluorescence. International reference preparations of cytokines with defined biological activity were spiked into (1) a defined medium simulating the composition of human vaginal fluid at pH 4.5 and 7.2, (2) physiologic salt solutions (phosphate-buffered saline and saline) commonly used for vaginal lavage sampling in clinical studies of cytokines, and (3) human blood serum. Assays were assessed for reproducibility, linearity, accuracy, and significantly detectable fold difference in cytokine level. Factors with significant impact on cytokine recovery were determined by Kruskal-Wallis analysis of variance with Dunn's multiple comparison test and multiple regression models. All assays showed acceptable intra-assay reproducibility; however, most were associated with significant interlaboratory variation. The smallest reliably detectable cytokine differences (P < 0.05) derived from pooled interlaboratory data varied from 1.5- to 26-fold depending on assay, cytokine, and matrix type. IL-6 but not IL-1[beta] determinations were lower in both saline and phosphate-buffered saline as compared to vaginal fluid matrix, with no significant effect of pH. The (electro)chemiluminescence-based assays were most discriminative and consistently detected < 2-fold differences within each matrix type. The Luminex-based assays were less discriminative with lower reproducibility between laboratories. These results suggest the need for uniform vaginal sampling techniques and a better understanding of immunoassay platform differences and cross-validation before the biological significance of cytokine variations can be validated in clinical trials. This investigation provides the first standardized analytic approach for assessing differences in mucosal cytokine levels and may improve strategies for monitoring immune responses at the vaginal mucosal interface.

Contraceptives that are readily available and acceptable are required in many poorer countries to reduce population growth and in all countries to prevent maternal morbidity and mortality arising from unintended pregnancies. Most available methods use hormonal steroids or are variations of barrier methods. Reports from several fora over the last 12 years have emphasized the number of unwanted pregnancies and resultant abortions, which indicate an unmet need for safe, acceptable, and inexpensive contraceptive methods. This unmet need can be assuaged, in part, by development of new nonhormonal contraceptive methods. This Review addresses the contribution that the "omic" revolution can make to the identification of novel contraceptive targets, as well as the progress that has been made for different target molecules under development., Retrospect More than 700,000 maternal deaths, most in the developing world and related to causes associated with unintended pregnancies, occurred between 1995 and 2000; more than 400,000 of these deaths [...]

Abstract Recently revised statistics show the number of individuals living with HIV at over 33 million worldwide, with 68% being in sub-Saharan Africa. Current HIV prevention methods, such as condom use, monogamy and abstinence, are not always feasible. The need for improved HIV preventative technologies remains urgent. Of these, microbicides represent a promising female-initiated preventative method. Microbicides are designed to be applied vaginally to prevent HIV and STI acquisition. Research is also being undertaken to assess the safety of the product during rectal application. The biannual Microbicides conference took place in New Delhi, India from 24–27 February 2008. The conference was open to delegates from the scientific and medical fields, as well as communities and advocates. In addition to microbicide research and development, the conference afforded the opportunity for the discussion of key issues such as ethics, acceptability, access, and community involvement. In this conference report we provide brief summaries of recent advancements made and challenges experienced in microbicide research and development, including updates on basic and clinical science, social and behavioural science, and community mobilisation and advocacy activities pertaining to clinical trials.

Abstract Background The continued growth of the global HIV epidemic highlights the urgent need to develop novel prevention strategies to reduce HIV transmission. The development of topical microbicides is likely to take a number of years before such a product would be widely available. This has resulted in a call for the rapid introduction of simpler vaginal intervention strategies in the interim period. One suggested practice would be vaginal douching with natural products including lime or lemon juice. Here we present a comprehensive preclinical evaluation of lime juice (LiJ) as a potential intervention strategy against HIV. Results Pre-treatment of HIV with LiJ demonstrated direct virucidal activity, with 10% juice inactivating the virus within 5 minutes. However, this activity was significantly reduced in the presence of seminal plasma, where inactivation required maintaining a 1:1 mixture of neat LiJ and seminal plasma for more than 5 minutes. Additionally, LiJ demonstrated both time and dose-dependent toxicity towards cervicovaginal epithelium, where exposure to 50% juice caused 75–90% toxicity within 5 minutes increasing to 95% by 30 minutes. Cervicovaginal epithelial cell monolayers were more susceptible to the effects of LiJ with 8.8% juice causing 50% toxicity after 5 minutes. Reconstructed stratified cervicovaginal epithelium appeared more resilient to LiJ toxicity with 30 minutes exposure to 50% LiJ having little effect on viability. However viability was reduced by 75% and 90% following 60 and 120 minutes exposure. Furthermore, repeat application (several times daily) of 25% LiJ caused 80–90% reduction in viability. Conclusion These data demonstrate that the virucidal activity of LiJ is severely compromised in the presence of seminal plasma. Potentially, to be effective against HIV in vivo, women would need to apply a volume of neat LiJ equal to that of an ejaculate, and maintain this ratio vaginally for 5–30 minutes after ejaculation. Data presented here suggest that this would have significant adverse effects on the genital mucosa. These data raise serious questions about the plausibility and safety of such a prevention approach.