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Background: Multipurpose prevention technologies that provide protection against HIV acquisition and unintended pregnancy, are safe and acceptable, and support flexible use, are critically needed. We report results from a Phase I study evaluating the safety, pharmacokinetics (PK), pharmacodynamics (PD), and acceptability of CONRAD's tenofovir/levonorgestrel (TFV/LNG) intravaginal ring (IVR) following 3 months of continuous or interrupted use in women. Methods: CONRAD A15-138 was an outpatient, randomized, partially blinded, placebo-controlled, parallel study conducted in Norfolk, VA and the Dominican Republic. Participants were healthy, 18 to 50 years old, had a body mass index Results: We screened 68 women; 47 were randomized onto study and 40 completed all visits. IVRs were safe with no significant changes in cervicovaginal epithelium, immune cell populations or soluble immune and inflammatory markers from baseline. Most TFV/LNG IVR users reported no change in their menstrual cycle or fewer/lighter bleeding days. Median vaginal fluid TFV concentrations were 546 to 3077 ng/mg throughout 90 days of use. Median TFV-DP tissue concentrations exceeded 1000 fmol/mg within 72 hours of IVR insertion. At 1 and 3 months of use, vaginal fluid of women using TFV/LNG IVRs had significantly greater inhibitory activity against HIV growth in vitro compared to baseline and to placebo (p < 0.01). TFV/LNG IVR users had mean serum LNG concentrations exceeding 200 pg/mL within 2 hours of IVR insertion. All placebo users ovulated each month, while only 39% to 71% of TFV/LNG users ovulated during months 1, 2 or 3, consistent with previously tested, effective contraceptive LNG IVRs. TFV/LNG IVR users had significantly lower cervical mucus (CM) Insler scores and a higher proportion of poor or abnormal in vitro CM sperm penetration (p < 0.05). Conclusions: The TFV/LNG IVR was safe, acceptable and delivered high TFV concentrations locally correlating with local PD. The micro-dose of LNG caused changes in CM, sperm penetration and ovulation compatible with contraceptive efficacy, while inducing acceptable changes in menstrual bleeding patterns., OA06.03 A. Thurman (1); V Brache (2); A.L. Ouattara (1); N. Chandra (1); T. Jacot (1); S. Jackson (1); M. Clark (1); M.M. Peet (1); H. Hanif (1); T. McCormick [...]

Background: The Population Council studied a pre-coital contraceptive microbicide vaginal product containing levonorgestrel (LNG) as active component and Carraguard gel as a vehicle (Carra/LNG gel) for couples who engage in occasional unplanned intercourse. The objective of this study was to evaluate the effect of sexual intercourse after vaginal application of Carra/LNG gel on serum levels of LNG in women and to assess LNG absorption by the male partner.Study Design: This was a randomized, cross-over, pharmacokinetic study including an abstinence arm and an arm in which couples engaged in sexual intercourse between 2 and 4 h after gel application. In each study arm, each woman received a single application of Carra/LNG gel (0.75 mg in 4 mL gel) followed by serial blood samples taken at 0, 1, 2, 4, 8, 24 and 48 h after gel application for LNG measurements. In the intercourse arm, LNG was measured in blood samples taken from the male partner before intercourse and at 4, 8 and 24 h after gel application in the female partner.Results: Time concentration curves for serum LNG levels showed a mean C(max) of 7.8+/-5.5 and 8.3+/-5.7 nmol/L, a mean T(max) of 6.2+/-5.9 and 7.5+/-5.7, and comparable area under the curve for the intercourse and abstinence arm, respectively. Pharmacokinetic parameters presented large variability between subjects, but excellent reproducibility within each subject. LNG was undetectable in 10 out of 12 male partners.Conclusion: Sexual intercourse does not appear to interfere with vaginal absorption of LNG after application of a Carra/LNG gel. A vaginal pre-coital contraceptive gel is feasible. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study was to determine the prevalence of enlarged follicles, as detected by a single clinical or ultrasonographic examination, among users of levonorgestrel subdermal contraceptive implants (Norplant implants).Study Design: This was a cross-sectional study of 103 users of Norplant implants and 50 users of the TCu380A intrauterine contraceptive device, all of whom received reproductive health services from PROFAMILIA, Santo Domingo, Dominican Republic. Bimanual pelvic examination and vaginal ultrasonography were performed. Enlarged follicles (>25 mm) were followed up weekly. The chi(2) test was applied to these data.Results: Enlarged follicles were detected by ultrasonography in 17. 5% of Norplant implants users and 4% of TCu380A intrauterine contraceptive device users, respectively (P <.04). There was no difference according to duration of use. The longest time to involution of the follicles was 4 weeks. Forty percent of the enlarged follicles detected by ultrasonography were also detected by bimanual pelvic examination.Conclusion: Enlarged follicles are a frequent finding among women who use Norplant implants, but they are less frequent than described in previous studies, which were based on serial ultrasonographic scans in selected groups of users. Physicians and users should be aware of the transient nature of these enlarged follicles, which do not require intervention. [ABSTRACT FROM AUTHOR]

The relationship between ovarian hormones and bleeding patterns during continuous progestin contraception was studied in 29 women who used Nestorone (NES) releasing implants. Oestradiol and progesterone were measured in blood samples taken twice a week for 6 consecutive weeks, during months 6, 12, 18 and 24 of implant use. Retrospectively, the association between hormonal concentrations and bleeding patterns was evaluated. Twenty-four short (

Objective: Our purpose was to evaluate whether prolonged or irregular bleeding during Norplant implant use could be alleviated with the use of oral hormonal medication.Study Design: One hundred fifty users of the Norplant levonorgestrel contraceptive implant with prolonged or frequent bleeding were enrolled in this prospective, randomized, comparative study and assigned to one of three treatment groups for 20 days: ethinyl estradiol 50 microg, an oral contraceptive (50 microg ethinyl estradiol and 250 microg levonogestrel), and placebo. Total days of bleeding during treatment and length of the bleeding-free interval were analyzed.Results: Women treated with the levonorgestrel-ethinyl estradiol pill bled an average of 2.6 days during treatment compared with 5.4 and 12.3 days in the ethinyl estradiol and placebo groups, respectively. Differences between both hormonal groups and placebo were significant (p <0.00001); moreover, the combined pill was more effective than ethinyl estradiol along (p <0.0001).Conclusion: The combined pill proved to be an excellent palliative treatment and is a more practical approach because of availability at all clinic sites. [ABSTRACT FROM AUTHOR]