Phase 1 randomized trials to assess safety, pharmacokinetics, and vaginal bleeding associated with use of extended duration dapivirine and levonorgestrel vaginal rings.

Background: Vaginal rings formulated to deliver two drugs simultaneously have potential as user-controlled, long-acting methods for dual prevention of HIV and pregnancy.

Methods: Two phase 1 randomized trials (MTN-030/IPM 041 and MTN-044/IPM 053/CCN019) respectively enrolled 24 and 25 healthy, HIV-negative participants to evaluate safety, pharmacokinetics, and vaginal bleeding associated with use of a vaginal ring containing 200mg dapivirine (DPV) and 320mg levonorgestrel (LNG) designed for 90-day use. MTN-030/IPM 041 compared the DPV/LNG ring to a DPV-only ring (200mg) over 14 days of use.

Participant experiences with a multipurpose vaginal ring for HIV and pregnancy prevention during a phase 1 clinical trial: learning from users to improve acceptability.

Introduction: With high concurrent global rates of HIV incidence and unintended pregnancy, there is a need to provide options beyond condoms to enable users to simultaneously prevent HIV acquisition and pregnancy. Multiple vaginal rings are in development as "MPTs" (multipurpose prevention technologies) as they are shown to provide several co-occurring benefits such as discretion, convenience, reversibility and user control.

Methods: In this Phase 1 trial of a 3-month MPT ring in the U.

Levonorgestrel 52-mg Intrauterine Device Efficacy and Safety After More Than 8 Years of Use.

Funding Source: Medicines360. The Sponsor, Medicines360, designed the study and oversaw its conduct, including funding the trial and providing all study product free of charge to participants.

Clinical Trial Registration: ClinicalTrials.

Dextromethorphan as a novel nonopioid adjunctive agent for pain control with medication abortion: A randomized controlled trial.

Objectives: To evaluate efficacy and satisfaction of dextromethorphan as a non-narcotic adjuvant to current analgesic regimens for medication abortion.

Study Design: We conducted a randomized, double-blinded, placebo-controlled trial. We randomized eligible participants (N = 156) 1:1 to adjunctively take dextromethorphan (loading dose 60 mg and two subsequent 30 mg doses at 2 and 5 hours after misoprostol administration) or placebo combined with usual-care nonsteroidal anti-inflammatory medications ± opioids for pain.

Early pregnancy confirmation availability at crisis pregnancy centers and abortion facilities in the United States.

Objectives: Crisis pregnancy centers (CPCs) seek to dissuade people from having abortions. Twenty-five states have policies supporting CPCs. We aimed: (1) to characterize access to early pregnancy confirmation at CPCs compared to abortion facilities nationwide and (2) to understand the role of state CPC policy in service access.

Increasing access to immediate postpartum contraceptive implants: a prospective clinical trial among patients with opioid use disorder.

Objective: To evaluate the effects of increased access to immediate postpartum contraceptive implants (IPI) on repeat pregnancy and contraceptive use rates among patients with opioid use disorder (OUD).

Materials And Methods: Between 2016 and 2018, 194 postpartum patients with OUD were offered the option of IPI placement at an institution with limited immediate postpartum long-acting reversible contraception availability and followed for one-year postpartum. Differences in pregnancy rates between participants who did and did not choose IPI were examined using logistic regression with inverse probability of treatment weighting from propensity scores accounting for differences between the two groups.

Continuation rates of two different-sized copper intrauterine devices among nulliparous women: Interim 12-month results of a single-blind, randomised, multicentre trial.

Background: The most widely used copper intrauterine device (IUD) in the world (the TCu380A), and the only product available in many countries, causes side effects and early removals for many users. These problems are exacerbated in nulliparous women, who have smaller uterine cavities compared to parous women. We compared first-year continuation rates and reasons/probabilities for early removal of the TCu380A versus a smaller Belgian copper IUD among nulliparous users.

Levonorgestrel 52 mg intrauterine system efficacy and safety through 8 years of use.

Background: Extending hormonal intrauterine system duration will allow users to have less need for procedures to provide long-term contraception.

Objective: This study aimed to evaluate the efficacy and safety of the levonorgestrel 52 mg intrauterine system during years 7 and 8 of use.

Study Design: A total of 1751 nulliparous and multiparous participants aged 16 to 45 years enrolled in a phase 3, multicenter trial to evaluate the efficacy and safety of the use of the Liletta levonorgestrel 52 mg intrauterine system for up to 10 years.

Acceptability of the Dapivirine Vaginal Ring in Postmenopausal US Women.

For women in the United States who remain sexually active beyond child-bearing years, susceptibility to HIV infection remains, yet condom use is low. We assessed acceptability of the dapivirine vaginal ring (ring) among 96 postmenopausal US women enrolled in a placebo-controlled multisite phase II trial of the ring, using questionnaires and in-depth interviews. Three quarters of women reported "perfect" adherence (ring never out) over the 3-month trial period.

Acceptability of an extended duration vaginal ring for HIV prevention and interest in a multi-purpose ring.

Given challenges with adherence to existing HIV prevention products, the development of an extended duration vaginal ring could improve adherence while reducing patient and provider burden. Additionally, women have other interlinked sexual health concerns such as unintended pregnancy. We evaluated acceptability of a 90-day ring to prevent HIV and hypothetical preferences for a dual (HIV and contraceptive) indication.

Users' Preferred Characteristics of Vaginal Rings for HIV Prevention: A Qualitative Analysis of Two Phase I Trials.

Vaginal rings address a critical need for an independently initiated, long-acting HIV prevention method, but their design must be acceptable to promote uptake and adherence. Human-centered design (HCD) may help address design preference questions. In two Phase I studies of vaginal rings for HIV prevention conducted in the United States, we used qualitative interviews to assess participants' perceptions and opinions of the physical characteristics of the ring they used and of a ring's physical characteristics after comparing four ring designs presented via a visual tool.

Impact of Dapivirine and Placebo Vaginal Rings on the Microbiota of Adolescent, Lactating, and Postmenopausal Females.

Background: A 25-mg dapivirine vaginal ring has been demonstrated to reduce risk of human immunodeficiency virus (HIV) acquisition in nonpregnant adult women. In this secondary analysis of studies conducted in US adolescent, lactating, and postmenopausal females, vaginal microbiota was assessed prior to and after ring use, and between dapivirine and placebo ring users.

Methods: Vaginal fluid swabs were collected before and after product use for the evaluation of microbiota using Nugent criteria, quantitative culture, and quantitative polymerase chain reaction.

Management of heterotopic pregnancy with uterine aspiration and systemic two-dose methotrexate.

The expected trend in serum beta-human chorionic gonadotropin (β-hCG) following treatment of an undesired heterotopic pregnancy with uterine aspiration and systemic methotrexate is not known. Thus, monitoring for treatment success is challenging. We describe an undesired heterotopic pregnancy treated with aspiration and two-dose methotrexate and report the observed β-hCG trend.

The legal and medical necessity of abortion care amid the COVID-19 pandemic.

In response to the COVID-19 pandemic, states have ordered the cessation of non-essential healthcare. Unfortunately, many conservative states have sought to capitalize on those orders to halt abortion care. In this short paper, we argue that abortion should not fall under any state's non-essential healthcare order.

Adherence to Recommended Practices for Provision of Long-Acting Reversible Contraception Among Providers in a Large U.S. Health Care System.

There is little research examining adherence to practice guidelines for long-acting reversible contraception (LARC). We assessed same-day LARC provision and adherence to other guideline-recommended practices among providers in a large academic health care system. We surveyed 363 providers who had billed using LARC-related codes within the prior 12 months.

Pharmacokinetic and Pharmacodynamic Impacts of Depot Medroxyprogesterone Acetate Use on HIV Pre-exposure Prophylaxis in Women.

Background: Depot medroxyprogesterone acetate (DMPA) is a commonly used contraceptive in areas where use of tenofovir disoproxil fumarate and emtricitabine for HIV pre-exposure prophylaxis (PrEP) is increasing.

Objectives: We aimed to investigate the impact of DMPA on PrEP drug pharmacokinetics and pharmacodynamics in women using PrEP before and after DMPA administration.

Methods: In this pilot study, 12 HIV-negative women ages 18-45 underwent biological sample collection at 3 time points: before study drug, after 2 weeks of daily PrEP use alone, and after 2 weeks of daily PrEP and concomitant DMPA use.

Bleeding changes after levonorgestrel 52-mg intrauterine system insertion for contraception in women with self-reported heavy menstrual bleeding.

Background: The levonorgestrel 52-mg intrauterine system has proven efficacy for heavy menstrual bleeding treatment in clinical trials, but few data exist to demonstrate how rapidly the effects occur and the effects in women with self-reported heavy bleeding, as seen commonly in clinical practice.

Objective: Evaluate changes in bleeding patterns in women with self-reported heavy menstrual bleeding before levonorgestrel 52-mg intrauterine system insertion.

Study Design: A total of 1714 women aged 16-45 years old received a levonorgestrel 52-mg intrauterine system in a multicenter trial evaluating contraceptive efficacy and safety for up to 10 years.

Effect of patient genetics on etonogestrel pharmacokinetics when combined with efavirenz or nevirapine ART.

Background: We previously demonstrated that etonogestrel concentrations were 82% lower in women using etonogestrel contraceptive implants plus efavirenz-based ART compared with women not receiving ART.

Objectives: To investigate the genetic contribution to this previously observed drug-drug interaction through studying SNPs in genes known to be involved in efavirenz, nevirapine or etonogestrel metabolism in the same group of women.

Patients And Methods: Here, we present a secondary analysis evaluating SNPs involved in efavirenz, nevirapine and etonogestrel metabolism and associated etonogestrel pharmacokinetics among 57 women, 19 not receiving ART (control group), 19 receiving efavirenz- (600 mg daily) based ART and 19 receiving nevirapine- (200 mg twice daily) based ART.

The Effect of Hormonal Contraception on Cervicovaginal Mucosal End Points Associated with HIV Acquisition.

Reproductive age women may choose to concurrently use topical antiretrovirals and hormonal contraceptives (HCs) to simultaneously prevent HIV-1 infection and unintended/mistimed pregnancy. There are conflicting data on the effect of HCs on mucosal susceptibility to HIV-1. The objective of this study was to evaluate cervicovaginal (CV) mucosal data from healthy women before and after initiation of either oral contraceptive pills (OCPs) or depot medroxyprogesterone acetate (DMPA) injection.

A Mixed-Methods Study Examining Adherence to and Acceptability of Intravaginal Rings for HIV Prevention: Behavioral Results of MTN-027.

Intravaginal rings (IVR) containing antiretroviral drugs are a promising method for HIV prevention. We triangulated quantitative and qualitative assessments to evaluate the acceptability of four IVRs used continuously for 28 days as part of a Phase I trial (N = 48 HIV-negative women; ages 18-45). Adherence was high throughout the trial, yet 30% of participants reported involuntary IVR expulsions followed by re-insertion.