Vaginal Ring Research Articles

Polymer Delivery Systems for Long-Acting Antiretroviral Drugs.

The success of long-acting (LA) drug delivery systems (DDSs) is linked to their biocompatible polymers. These are used for extended therapeutic release. For treatment or prevention of human immune deficiency virus type one (HIV-1) infection, LA DDSs hold promise for improved regimen adherence and reduced toxicities. Current examples include Cabenuva, Apretude, and Sunlenca. Each is safe and effective. Alternative promising DDSs include implants, prodrugs, vaginal rings, and microarray patches. Each can further meet patients' needs. We posit that the physicochemical properties of the formulation chemical design can optimize drug release profiles. We posit that the strategic design of LA DDS polymers will further improve controlled drug release to simplify dosing schedules and improve regimen adherence.

Comparison of Combined Parenteral and Oral Hormonal Contraceptives: A Systematic Review and Meta-Analysis of Randomized Trials.

Delivering contraceptive hormones through a transdermal patch or a vaginal ring might have advantages over the traditional oral route. To compare the effectiveness, compliance, and side effect profile of oral and parenteral drug administration methods. We performed a systematic literature search in four medical databases-MEDLINE (via PubMed), Cochrane Library (CENTRAL), Embase, and Scopus-from inception to 20 November 2022. Randomized controlled trials assessing the efficacy, compliance, and adverse event profile of combined parenteral and oral hormonal contraceptives were included. Our systematic search provided 3952 records; after duplicate removal, we screened 2707 duplicate-free records. A total of 13 eligible studies were identified after title, abstract, and full-text selection. We observed no significant difference in contraceptive efficacy (Pearl Index) between oral and parenteral drug administration (MD = -0.06, CI: -0.66-0.53; I2 = 0%). We found significant subgroup differences between parenteral methods in terms of compliance (χ2 = 4.32, p =0.038, I2 = 80%) and certain adverse events: breast discomfort (χ2 = 19.04, p =0.001, I2 = 80%), nausea (χ2 = 8.04, p =0.005, I2 = 75%), and vomiting (χ2 = 9.30, p =0.002; I2 = 72%). Both parenteral and oral contraceptives can be used as an effective contraceptive method, and the route of administration should be tailored to patient needs and adverse event occurrence.

Successful postcoital testing of Ovaprene: An investigational non-hormonal monthly vaginal contraceptive

ObjectiveEvaluate reduction in progressively motile sperm per high power field (HPF) in midcycle cervical mucus after intercourse with Ovaprene: an investigational monthly non-hormonal vaginal contraceptive consisting of a vaginal ring and mechanical barrier, releasing spermiostatic ferrous gluconate. Study designOpen-label, multicenter study enrolling heterosexually-active women with previous permanent contraception. Participants underwent a baseline postcoital test cycle with no device to confirm the presence of sperm, followed by one diaphragm postcoital test cycle, one Ovaprene safety cycle, and two Ovaprene postcoital test cycles. In each postcoital test cycle, participants underwent a midcycle cervical mucus evaluation to confirm an Insler score ≥10 and absence of sperm, and then returned two to four hours after vaginal intercourse for repeat cervical mucus evaluation. We considered <5 progressively motile sperm/HPF indicative of preliminary contraceptive effectiveness. ResultsWe enrolled 38 participants; 23 completed the study. All participants had ≥5 progressively motile sperm/HPF in the baseline cycle and <5 progressively motile sperm/HPF in all 49 Ovaprene cycles and all 35 diaphragm cycles, meeting the definition of a successful postcoital test. This was true regardless of examiner blinding, prior vaginal delivery or vaginal ring use, body mass index, or dislodgements noted by the participant or investigator. The mean of 27.2 (±17.9) progressively motile sperm/HPF in baseline postcoital test cycles was reduced to 0.5 (±1.1) and 0.5 (±1.3) progressively motile sperm/HPF in the first and second Ovaprene cycles, respectively. Ovaprene fit all participants and all could insert, position, and remove it. ConclusionUse of Ovaprene resulted in meeting the prespecified criterion for contraceptive effect by all participants during all postcoital test cycles. ImplicationsThe finding that use of Ovaprene, an investigational monthly non-hormonal vaginal contraceptive, resulted in postcoital testing of cervical mucus that met the pre-specified definition of success (<5 progressively motile sperm/HPF) supports further evaluation of contraceptive efficacy of the device in users at risk for pregnancy.

Long-term continuations rate of ring pessary use for symptomatic pelvic organ prolapse.

To evaluate long-term continuation rates, adverse events of ring pessary use at a minimum of 5years follow-up, and factors associated with discontinuation in symptomatic pelvic organ prolapse (POP). Women with symptomatic POP who were treated with vaginal ring pessary and had successful fittings were included. Adverse events and reasons for discontinuation of pessary use were recorded. Patients who were lost to follow-up were defined as discontinuation. During 12year-period, 239 of 329 POP patients (72.6%) had successful fittings with ring pessary. The mean age was 67.8 ± 8.9years (range 27-86) and 70% of patients had advanced stage. The cumulative probability of continued ring pessary use was 84.1%, 64.4%, 49.3%, and 33.5%, at 1, 3, 5, and 10years, respectively. Most common reason for discontinuation was frequent expulsion (21.6%), followed by vaginal erosion (16.5%), no prolapse improvement (12.4%), and inability or inconvenience to do self-care (9.3%). However, 9 patients (9.3%) had improvement of prolapse and were able to discontinue pessary insertion. Age above 70years, wide introitus, and incapability of self-care are independent factors associated with long-term discontinuation. Adverse events occurred in 23.4% of patients, 18.8% of them had vaginal erosion, 11.7% vaginal discharge/infection, and 18.4% de novo SUI. However, no statistical significance existed between those who continued and discontinued pessary use due to these adverse events. Ring pessary is an effective treatment in symptomatic POP, with acceptable long-term continuation rates and minor adverse events. Self-care of pessary is very important aiming to minimize adverse events. Advanced age, wide introitus and incapability of self-care were associated factors for long-term discontinuation.

Barriers to Oral PrEP: A Qualitative Study of Female Sex Workers, PrEP Prescribers, Policymakers, and Community Advocates in Morocco.

In 2017, Morocco became the first Arab country to incorporate pre-exposure prophylaxis (PrEP) in its HIV-prevention program. Yet no research has been published on PrEP from Morocco. Although female sex workers are one of the target populations of PrEP in Morocco, their enrollment in PrEP is lower than men who have sex with men. In this study, we conducted 38 semi-structured interviews with female sex workers, physicians who prescribe PrEP, policymakers, and community advocates to identify problems associated with access to and use of PrEP. We also investigated preferences for daily oral, vaginal ring, and long-acting injectable PrEP. A reflexive thematic analysis revealed seven themes: PrEP stigma; stigmatization and criminalization of sex work; one size doesn't fit all; knowledge and misconceptions about PrEP; economic burden; inconvenience of PrEP pills; and preferred PrEP modalities. This paper discusses the implications of the findings for increasing access and use of PrEP in Morocco.

The role of economic evaluations in advancing HIV multipurpose prevention technologies in early-stage development.

Product development is a high-risk undertaking, especially so when investments are prioritized for low- and middle-income countries (LMICs) where markets may be smaller, fragile, and resource-constrained. New HIV prevention technologies, such as the dapivirine vaginal ring (DVR) and long-acting injectable cabotegravir (CAB-LA), are being introduced to these markets with one indication, meeting different needs of groups such as adolescent girls and young women (AGYW) and female sex workers (FSWs) in settings with high HIV burden. However, limited supply and demand have made their uptake a challenge. Economic evaluations conducted before Phase III trials can help optimize the potential public health value proposition of products in early-stage research and development (R&D), targeting investments in the development pathway that result in products likely to be available and taken up. Public investors in the HIV prevention pipeline, in particular those focused on innovative presentations such as multipurpose prevention technologies (MPTs), can leverage early economic evaluations to understand the intrinsic uncertainty in market characterization. In this perspective piece, we reflect on the role of economic evaluations in early product development and on methodological considerations that are central to these analyses. We also discuss methods, in quantitative and qualitative research that can be deployed in early economic evaluations to address uncertainty, with examples applied to the development of future technologies for HIV prevention and MPTs.

Contraceptive Methods and Female Sexual Function: A Literature Review

Contraceptives can affect libido, and method choice should consider possible effects on female sexual function. This review aims at identifying the role of different contraceptive methods on female sexual function, thus allowing for better clinical counseling. This review, performed in August/2022, included 13 reviews and 32 clinical trials. The levonorgestrel intrauterine system, vaginal ring, and transdermal patch showed mainly positive or neutral effects. The subcutaneous implant and combined oral contraceptives led to mixed results. The progestogen-only oral contraceptive and the DMPA intramuscular injection were associated with mainly negative sexual effects. The copper uterine device had no impact on female sexual function. Sterilization had mixed psychological effects. Adequate counseling, replacement of the contraceptive method, and, in specific cases, pharmacologic treatment may improve contraceptive-associated female sexual dysfunction. More large-scale studies are needed to allow for specific recommendations regarding each contraceptive method and the production of clinical guidelines for these situations.

Abortion by request in advanced maternal age: What changes in contraception?

Overview and aimPregnancy at an advanced maternal age has become a reality. The acceptance rate of an unwanted pregnancy in this age group is lower, resulting in a higher proportion of pregnancy interruptions. This study aims to characterize abortion by request (AR) in advanced maternal age. MethodsDescriptive study of AR requested by women aged 40 years old or older, over a period of six years, in an Obstetrics service of a Portuguese tertiary hospital. Descriptive data analysis was performed using SPSS® version 26. Results194 women were included in the study (n=194), with a median age of 42 years, most of them Portuguese (94.3%) and with no history of performing AR (75.2%). The contraceptive methods used prior to AR were used oral contraception (47.0%) and barrier contraception (39.1%). Medical abortion was performed in the entire sample, with a success rate of 96.9%. After AR, intrauterine contraception (44.3%), oral contraception (22.7%) and the vaginal ring (7.2%) were the preferred contraceptive methods. Discussion/ConclusionsChanges in women's health and contraceptive needs motivate new approaches and contraceptive strategies. After AR, a significant percentage of woman chose long-term and non-user-dependent methods. Particularly in women aged 40 or over, these methods, in addition to their highly effective and safe contraceptive role, may bring additional non-contraceptive benefits, namely the therapeutic effect in abnormal uterine bleeding.

Hormonal Contraception and Menopausal Hormone Therapy: A Reference for Orthopaedic Surgeons

BACKGROUND: Exogenous estrogen is a double-edged sword in the realm of orthopaedic surgery, providing many musculoskeletal health benefits to menopausal women yet adding an additional risk of venous thromboembolism (VTE) in the perioperative setting for patients using certain forms of hormonal contraception and menopausal hormone therapy (MHT). The primary objective of this review is to summarize the known literature regarding the VTE risks of perioperative medications containing exogenous estrogen among orthopaedic patients. A secondary objective is to provide guidance to orthopaedic surgeons regarding perioperative management of commonly encountered forms of hormonal contraception and MHT. METHODS: A summative review of existing literature regarding VTE risk of various forms of hormonal contraception and MHT is provided, with emphasis on perioperative VTE risk surrounding major and minor orthopaedic surgery. RESULTS: Increased risk of VTE has been identified after arthroscopic knee procedures in patients utilizing oral contraceptive pills and after major lower extremity surgery in patients using MHT, yet there is not a clear standard of care as to how to manage these medications after surgery or how and when to adjust VTE prophylaxis. Regardless of the mode of delivery (pills, patches, vaginal rings), hormonal contraception with exogenous estrogen carries some associated VTE risk that can be compounded by surgery. Depo-Provera has also demonstrated increased risk. Forms of hormonal contraception without elevated VTE risk are progestin only pills and intrauterine devices (IUDs) as well as Nexplanon. MHT with systemic level doses of exogenous estrogen delivered orally has associated VTE risk. While systemic transdermal and transvaginal formulations of estrogen have not been shown to increase VTE risk in the non-surgical state, the risk when combined with the perioperative state after major operations is not yet known. Local estrogen therapies for vaginal symptoms of menopause do not increase risk of VTE. CONCLUSION: Given the frequent utilization of hormonal contraception and MHT, orthopaedic surgeons should consider the use of medications containing exogenous estrogen in the perioperative VTE risk assessment of patients. Further discussion toward the perioperative management of these medications and standardization of care for patients with increased VTE risks should be encouraged.

Laboratory evaluation of the hormonal agents effects on the plasma hemostasis system in women of reproductive age

Background: With the evolution of hormonal contraception, such as implementation of low dose agents, new regiments and administration routes of contraceptives, the risk of thrombotic complications persists, although is decreasing. The search for an available test for hemostasis assessment, which would allow for the prediction of thrombotic complications in high risk patients, remains relevant. Global tests for hemostasis assessment, such as thrombin generation test and thrombodynamics test, are attracting the specialists' attention due to the possibility of a quick integrative assessment of plasma hemostasis, especially during choice and tailoring of an optimal version of hormonal therapy.&#x0D; Aim: To assess the value of the integral thrombodynamics test in the multifactorial assessment of hemostasis system in women of reproductive age using hormonal contraceptives.&#x0D; Materials and methods: This observational prospective comparative study included 408 women aged 18 to 49 years followed from 2018 to 2022 in The Nikiforov Russian Center of Emergency and Radiation Medicine and Centre of Miscarriage Prevention and Treatment of the Maternity Hospital No. 1, St. Petersburg. From these, 208 women (mean age, 38.0 ± 7.0 years) were taking hormonal contraceptives (HC+ group), and 200 women (mean age, 37.5 ± 9.2 years) were in the control group (HC-). In the HC+ group, 163 women were taking combination oral contraceptives, 24 had an intrauterine levonorgestrel-releasing system, 8 used vaginal rings, and 13 were using progestin only oral contraceptives. Multifactorial clinical and laboratory assessment included taking past history, measurement of pro- and anticoagulation blood parameters, fibrinolysis, and endothelial function parameters (automatic coagulometer ACL TOP 500, Instrumentation Laboratory, USA). The integral assessment of the hemostasis system was performed with Thrombodynamics Registrator T-2 (Hemacor, Russia).&#x0D; Results: The groups were similar as per their age, chronic venous insufficiency and smoking. The HC+ group had significantly higher proportion of women with cardiovascular disorders (p = 0.0037), obesity (p = 0.0004), and headache (p 0.0001), compared to the HC- group. The thrombodynamics test showed a significantly higher rate of clot formation in the women taking hormonal contraception, compared to that in the HC- group (36.2 [30.1; 43.6] and 30.3 [28.0; 33.6] mcm/min, respectively, р 0.001). Hypercoagulation identified by the thrombodynamics test was associated with slowing down of XIIа-dependent fibrinolysis (6 [5; 8] min in the HC- and 12.8 [8; 16] min in the HC+ group, p 0,001) and higher levels of endothelial dysfunction markers (FVIII, 113 [85; 156] and 150 [107; 180]%, p = 0.015; vFW, 98 [85; 133] and 146 [95; 168]%, respectively, p = 0.003). The analysis of plasma hemostasis parameters depending on the presence of thromboembolic risk factors has shown that higher number of the risk factors is associated with higher velocity parameters in the thrombodynamics test in the range of chronometric hypercoagulation.&#x0D; Conclusion: The integral thrombodynamics test for the assessment of plasma hemostasis allows for identification of hemostasis dysfunction in women taking hormonal contraceptives. To prevent the risk of thromboembolic complications, it is desirable to assess blood coagulation system parameters before administration of hormonal agents.

HIV Pre-Exposure Prophylaxis: New and Upcoming Drugs to Address the HIV Epidemic.

Human immunodeficiency virus (HIV) pre-exposure prophylaxis (PrEP) provides a critical intervention toward ending the HIV epidemic and protecting people with reasons to utilize PrEP. PrEP options continue to expand as new administration modalities offer the potential to tailor PrEP use for individual success. We have provided the evidence for new and emerging antiretroviral agents for PrEP (cabotegravir, lenacapavir, dapivirine, and broadly neutralizing antibodies), divided into pharmacology, animal model, and human data, accompanied by a summary and suggested place in therapy. Cabotegravir is a US Food and Drug Administration (FDA)-approved intramuscular injection given every 2 months with a strong body of evidence demonstrating efficacy for HIV PrEP, lenacapavir administered subcutaneously every 6 months is currently under investigation for HIV PrEP, dapivirine vaginal ring is an available PrEP option for women in certain areas of Africa, and broadly neutralizing monoclonal antibodies have been challenged in demonstrating efficacy in phase 1-2 study for HIV PrEP to date. Clinical literature for individual agents is discussed with data from major studies summarized in tables. This review provides a detailed overview of recently available and premier candidate PrEP drugs.

Efficient regulatory approval of two novel HIV prevention interventions in a resource-limited setting: experiences from Zimbabwe.

The global burden of HIV remains unacceptably high despite significant progress made in HIV treatment and prevention. There is an urgent need to scale up the comprehensive HIV prevention strategies that include pre-exposure prophylaxis (PrEP). Oral PrEP is highly effective in preventing HIV acquisition when taken regularly, but this remains a challenge for some at-risk individuals. Therefore, there is a need for other HIV prevention options. The dapivirine vaginal ring (DVR) and long-acting injectable cabotegravir (CAB-LA) are novel biomedical interventions that are safe and efficacious for HIV pre-exposure prophylaxis, as demonstrated in recently completed clinical trials. Timely roll-out and scalability of efficacious interventions depend on the registration process with the national medicine regulatory authorities (NMRAs). The Medicines Control Authority of Zimbabwe (MCAZ) was the first NMRA globally to approve the DVR in July 2021 and the first in Africa to approve CAB-LA for HIV prevention in July 2022. The regulatory review process for DVR and CAB-LA by MCAZ took 4.5 and 5.5 months, respectively. This efficient review process of the two interventions by MCAZ, a regulatory body in a resource-limited setting, provides important lessons to shorten timelines between the completion of the clinical development process and the registration of essential medicines.

Acceptability of the Dapivirine Vaginal Ring and Oral Truvada Among African Users in Late-Stage of Pregnancy

The Microbicide Trials Network 042 study (MTN-042/DELIVER) is a two-arm, randomized, open-label Phase 3b trial that is evaluating the safety, adherence, and acceptability of the monthly ring and daily oral PrEP among HIV-uninfected pregnant people in four African countries. This analysis focuses on acceptability data captured qualitatively from a subset (n = 48) of the 150 people in the first cohort of the trial who were enrolled in late-stage pregnancy at 36 to 38 weeks gestational age and followed until after delivery. Single IDIs were conducted by trained interviewers at each clinic site using a semi-structured guide. Data excerpts of key codes pertaining to acceptability, pregnancy, and maternal health were summarized, reviewed and interpreted by multinational analyst teams. Although the product use period was relatively short, the data suggested several acceptability findings that may directly translate to longer durations of product use in pregnancy. The first was the overarching maternal sentiment that being able to protect both oneself and their baby was highly valued. The second was the importance of counseling support from providers not only because participants used methods that might generate side effects, but because pregnancy itself is a period with its own set of side effects. The third was that, similar to non-pregnant participants in other trials, here study products were generally liked and described as easy to use. Concerns about ring and oral PrEP use could be addressed with provider counseling and support and should form an essential component rollout among pregnant people.

Two into one does go: Formulation development of a multipurpose combination vaginal ring releasing dapivirine and metronidazole for prevention of HIV infection and treatment of bacterial vaginosis

Bacterial vaginosis (BV) is a common but often asymptomatic dysbiosis of the human vagina characterized by an imbalance in the normal vaginal microbiota due to loss of lactobacilli and an overgrowth of certain anaerobic bacteria. While BV itself is not a sexually transmitted infection, it is associated with an increased risk in women of various sexually acquired infections, including human immunodeficiency virus (HIV) infection. There is, therefore, a strong rationale for pursuing new multipurpose products that seek to treat or prevent BV alongside preventing HIV infection. With the dapivirine-releasing vaginal ring for HIV prevention now approved in several African countries, here we report formulation development of a next-generation ring product that releases both dapivirine (DPV) and the antibiotic drug metronidazole (MET). Following thermal analysis studies to characterize the phase behaviour of DPV-MET mixtures and rheological analysis to assess the cure characteristics of the active silicone elastomer mixes, matrix-type rings were manufactured containing 25 or 200 mg DPV in combination with 100, 250, 500, 1000 or 2000 mg MET. The results for drug content, in vitro release, mechanical testing, and Gardnerella vaginalis time-kill experiments demonstrate the feasibility of incorporating both DPV and MET in a matrix-type ring formulation and indicate that clinically effective release rates may be possible.

“It’s already in your body and it’s preventing”: a qualitative study of African female adolescent’s acceptability and preferences for proxy HIV prevention methods in Cape Town, South Africa

BackgroundAdvances in biomedical HIV prevention will soon offer young women a choice of HIV prevention methods, including various pre-exposure prophylaxis (PrEP) modalities such as daily oral pills, dapivirine vaginal ring, and long-acting injectable agents. By understanding preferences for contraceptive methods, we may draw analogies for the HIV prevention needs of young women.The UChoose Study was an open-label randomised cross-over study designed to evaluate the acceptability and preference for several contraceptive options as a proxy for HIV prevention methods that use similar types of administration. The study enrolled healthy HIV uninfected young women aged 15 to 19 years. At enrolment, participants were randomly assigned to a contraceptive method for a period of 16 weeks in the form of monthly Nuvaring® (vaginal ring), daily combined oral contraceptive (daily pills), or bi-monthly injectable contraceptive (injectable). After 16 weeks, participants crossed over to another contraceptive method, and those who had received the injectable and the daily pills received the vaginal ring for another 16 weeks, whereas those who had received the vaginal ring were able to choose between the injectable and daily pills, to ensure that all participants tried the vaginal ring—the least familiar option to the study population.ResultsThirty-three participants were purposively recruited to participate in seven focus group discussions (FGD) and completed a pre-survey for their assigned group. Our sample comprised 14 participants randomised to use of the vaginal ring and daily pills and 19 participants randomised to use of the vaginal ring and injectable. For most participants, their preferences for a prevention method were based primarily on their desire to avoid negative aspects of one method rather than their positive user experience with another method. Most participants expressed initial hesitancy for trying new contraception method products; however, a lack of familiarity was moderated by a strong interest in diverse user-controlled prevention methods. Participants valued methods that had infrequent dosing and simplified use requirements. The injection and vaginal ring were preferred over daily pills as a potential HIV prevention method.ConclusionExpanding the availability of diverse products could provide adolescents with multiple choices in HIV prevention for the uninitiated.Trial registrationClinicalTrials.gov (NCT02404038). Registered March 31, 2015—Registered.

Prevention strategies for sexually transmitted infections, HIV, and viral hepatitis in Europe.

The current prevention efforts for STIs, HIV and viral hepatitis in the WHO European Region, especially in the Central and Eastern subregions, are hindered by healthcare disparities, data gaps, and limited resources. In this comprehensive narrative review, we aim to highlight both achievements and persisting challenges while also exploring new developments that could significantly impact the prevention of these infections in the near future. While pre-exposure prophylaxis (PrEP) for HIV has been broadly approved and implemented in 38 out of 53 countries in the region, challenges remain, including cost, limited licensing, and incomplete adherence. We explore innovative approaches like on-demand PrEP, long-acting injectable cabotegravir, and intravaginal rings that have shown promising results, alongside the use of six-monthly lenacapavir, the outcomes of which are pending. Additionally, the potential of doxycycline post-exposure prophylaxis has been discussed, revealing efficacy in reducing chlamydia and syphilis risk, but effectiveness against gonorrhoea being contingent on tetracycline resistance rates, and the need of further data to determine potential resistance development in other bacteria and its impact on the gut microbiome. We examine successful vaccination campaigns against HBV and HPV, the ongoing development of vaccines for chlamydia, syphilis, herpesvirus, and gonorrhoea, and challenges in HIV vaccine research, including lines of research with significant potential like sequential immunization, T-cell responses, and mRNA technology. This review underscores the research endeavors that pave the way for a more resilient and robust approach to combating STIs, HIV, and viral hepatitis in the region.

Adherence, safety, and choice of the monthly dapivirine vaginal ring or oral emtricitabine plus tenofovir disoproxil fumarate for HIV pre-exposure prophylaxis among African adolescent girls and young women: a randomised, open-label, crossover trial

Half of new HIV acquisitions in Africa occur in adolescent girls and young women. Pre-exposure prophylaxis (PrEP) with oral tenofovir disoproxil fumarate plus emtricitabine or the monthly dapivirine vaginal ring is efficacious but has lower adherence and effectiveness among adolescent girls and young women. We aimed to assess product adherence, safety, and choice of oral PrEP compared with the dapivirine ring among African adolescent girls and young women. MTN-034/REACH was a randomised, open-label, phase 2a crossover trial among HIV-seronegative, non-pregnant adolescent girls and young women aged 16-21 years at four clinical research sites in South Africa, Uganda, and Zimbabwe. Participants were randomly assigned (1:1) to either the dapivirine ring or daily oral PrEP (200 mg of emtricitabine and 300 mg of tenofovir disoproxil fumarate) for 6 months, then switched to the other product option for 6 months, followed by a third 6-month period in which participants were given a choice of oral PrEP, the dapivirine ring, or neither. Fixed block randomisation was used, stratified by site. The primary adherence endpoint was use of each product during the randomised periods, with high use defined as tenofovir-diphosphate concentrations greater than or equal to 700 fmol/punch (associated with taking an average of four or more tablets per week in the previous month) and greater than or equal to 4 mg dapivirine released from the returned ring (continuous use for 28 days in the previous month) based on residual drug concentrations. The primary safety endpoint was grade 2 or higher adverse events during each randomised period of 24 weeks of ring and oral PrEP. This trial is registered at ClinicalTrials.gov, NCT03593655. From Feb 6, 2019 to Sept 9, 2021, 396 adolescent girls and young women were screened, 247 of whom were enrolled and randomly assigned (6 months of the ring followed by 6 months of oral PrEP n=124; 6 months of oral PrEP followed by 6 months of the ring n=123). Median age was 18 years (IQR 17-19). 54 grade 2 or higher product-related adverse events were reported during oral PrEP and five during dapivirine ring use, with no product-related serious adverse events. High adherence was observed in 753 (57%) of the 1316 oral PrEP visits and 806 (57%) of the 1407 dapivirine ring visits. Four women acquired HIV during follow-up. Adherence was moderately high and similar between oral PrEP and the dapivirine ring with favourable safety and tolerability. Oral PrEP and the dapivirine ring are effective, safe, and well tolerated HIV prevention options for adolescent girls and young women who would benefit from a choice of PrEP formulations to meet their needs and preferences. National Institutes of Health.

Contraceptive effects on the cervicovaginal microbiome: Recent evidence including randomized trials.

Until recently, most data regarding the effects of non-barrier contraceptives on the mucosal microbiome have derived from observational studies, which are potentially biased due to behavioral confounders that may mask their true biological effects. This narrative review summarises recent evidence of the effect of contraceptives on the cervicovaginal microbiome, emphasising data obtained through randomized trials. Good quality data describe that initiation of long-acting progestin-only contraceptives, including levonorgestrel (LNG)-implant and the injectables depot-medroxyprogesterone acetate (DMPA-IM) and norethisterone enanthate (NET-EN) do not alter the mucosal microbial environment. Likewise, no strong evidence exists that the use of oral contraceptive pills (OCPs) is associated with alterations of the vaginal microbiome or increased risk of bacterial sexually transmitted infections (STIs). Limited data on the effect of intravaginal rings (IVRs) on the mucosal environment exist and show conflicting effects on the vaginal microbiota. Copper intrauterine device (Cu-IUD) initiation has been associated with bacterial vaginosis (BV) acquisition, including in a randomized trial. LNG-IUDs may have similar affects but need to be evaluated further. Different synthetic hormones have divergent effects on the microbiome and therefore novel hormonal methods need to be rigorously evaluated. Furthermore, the addition of antiretrovirals into multipurpose technologies may alter the effects of the hormonal component. There is thus a critical need to improve our understanding of the biological effects of contraceptive hormones and delivery methods with different pharmacokinetic and chemical properties on the mucosal microbiome in rigorous trials, to inform the development of novel contraceptives and improve individual family planning guidance.

Access to on-campus contraception on college and university campuses in North Carolina

Background and ObjectiveUnintended pregnancies occur more frequently in college students and negatively affect health outcomes and educational attainment. This study examined access to on-campus contraceptives at all 4-year colleges and universities in North Carolina (NC). MethodsThis institutional review board-exempt study evaluated availability of on-campus contraceptives including condoms; hormonal contraceptives including pills, patches, and vaginal rings; medroxyprogesterone injections; implants; intrauterine devices; and emergency contraception via website review. Institutions were stratified by characteristics including size, location, type (e.g., public, private, religious affiliation, historically black colleges and universities, women’s colleges), and presence of a student health pharmacy. Comparisons were made using chi-square test or Fisher’s exact test. ResultsFifty-four 4-year colleges and universities were identified. A plurality or the majority of schools were considered small (41%) and urban (48%) and had a religious affiliation (61%). Thirty-three percent of colleges and universities had an on-campus pharmacy. The most frequent contraceptives offered were condoms (43%), oral contraceptives (33%), and medroxyprogesterone injections (22%). Emergency contraception was available at approximately one-third of colleges and universities. Six percent of institutions provided a full range of contraceptive methods. Contraceptives were offered more frequently at large, public, urban institutions, whereas religious institutions and smaller institutions were less likely to offer contraceptives. ConclusionAccess to on-campus contraception for college students in NC is lacking, and the vast majority of institutions did not provide a full range of contraceptives. Policy measures, such as enhancing reproductive health services at student health centers or increasing contraception availability directly through pharmacies, are needed to improve access for college students.

A stakeholder-developed logic model to improve utilization of pharmacy-prescribed contraception in Utah

BackgroundCurrently, 20 states in the USA have passed policies allowing pharmacists to prescribe short-acting hormonal contraception, including pills, patches, and vaginal rings. Yet, utilization of these services remains limited. The purpose of this study was to (a) assess barriers and facilitators of pharmacy contraceptive dispensing among contraceptive users, pharmacists, and healthcare providers in Utah and (b) adapt and propose an evidence-based contraceptive intervention in the pharmacy environment.MethodsWe conducted 6 focus groups among contraceptive users, pharmacists, and healthcare providers assessing current barriers and facilitators to pharmacy prescribing. We coded transcripts of these focus groups to the Consolidated Framework for Implementation Research, Version 2.0 (CFIR) and characterized the findings based on the Expert Recommendations for Implementing Change (ERIC) Barrier-Busting tool. Based on the CFIR findings and ERIC strategies output, we adapted an existing evidence-based intervention (a contraceptive access initiative) to the Utah pharmacy environment. We then convened a pharmacy stakeholder meeting and presented elements of an Implementation Research Logic Model and obtained feedback. We coded this feedback to the CFIR framework to finalize an Implementation Research Logic Model for a proposed implementation approach to improving contraceptive prescribing.ResultsInitial focus group responses clustered around specific implementation barriers including financial barriers (cost for patients, as well as lack of reimbursement for pharmacist’s time); lack of awareness of the service (on the part of patients, pharmacists, and health care providers); need for updated tools for contraceptive counseling and scheduling; and need for increased pharmacists education to conduct contraceptive counseling. Proposed adaptations to the existing contraceptive access intervention included development of a technology-based patient/pharmacist screener tool and a healthcare provider/pharmacist contraceptive referral network. Stakeholders identified pharmacist reimbursement as the top priority for improving utilization.ConclusionsElements of contraceptive access initiatives mapped well as proposed implementation strategies to improving utilization of contraceptive prescribing in pharmacies.