Associations between intravaginal practices and incidence of sexually transmitted infections and bacterial vaginosis among women enrolled in the dapivirine vaginal ring trial (The Ring Study) in southwestern Uganda: a retrospective secondary analysis.

OBJECTIVES: We assessed associations between intravaginal practices (IVPs) and the incidence of sexually transmitted infections (STIs) and bacterial vaginosis (BV) among women using the dapivirine vaginal ring (DVR) or placebo vaginal ring in southwestern Uganda. METHODS: This was a retrospective secondary analysis of data collected from women at risk of HIV infection recruited into the Ring Study. The latter evaluated the safety and efficacy of the DVR between 2013 and 2016. At baseline, a behavioural questionnaire was administered to obtain information on sexual activity and IVP (exposure) defined as; insertion inside the vagina of any items aimed at cleaning the vagina for any reason before, during or after sex other than practices to manage menses. Each participant self-inserted the DVR/placebo and replaced it every 4 weeks for 2 years. Outcomes were diagnosis of STIs, that is, Chlamydia trachomatis, Neisseria gonorrhoea, Trichomonas vaginalis (TV), HIV and BV. The incidence rate of STI/BV was estimated, overall, by IVP and trial arm in single-event-per-participant and multiple-event-per-participant analyses. RESULTS: Of the 197 women enrolled, 66 (33.5%) were <25 years of age. Overall, 93 (47.2%) practised at least one form of IVP. During the follow-up, 172 (87.3%) women were diagnosed with an STI/BV at least once. The majority had TV (73.6%, n=145). Overall rate of STI/BV was 51.9/100 person-years, 95% CI 44.7 to 60.3 (IVP: yes, 51.0 (40.8-63.8) vs no, 52.6 (43.0-64.4)). IVPs were not statistically significantly associated with rate of individual STIs/BV. Similar results were observed when the analyses were conducted separately for each trial arm. CONCLUSIONS: IVP was not associated with risk of STIs/BV in the Ring Study. TRIAL REGISTRATION NUMBER: NCT01539226.

A nine-month repeat-dose intravaginal ring (Ovaprene) irritation study in sheep.

OBJECTIVES: Ovaprene is a novel, investigational, intravaginal hormone-free monthly ring contraceptive designed for use in women of reproductive age to be worn over multiple weeks (one menstrual cycle). The objective of this work was to evaluate the safety of Ovaprene during a nine-month repeat-dose sheep study. STUDY DESIGN: In addition to traditional safety endpoints such as histopathological evaluation of the sheep female reproductive tract, vaginal fluids were collected and tested for released iron over time. Also, the amount of iron in the rings was assessed following removal, and serum iron levels were measured. There were four sheep in each group (Ovaprene group and sham group). RESULTS: There were no macroscopic clinical findings. There was minimal to mild, mixed or mononuclear cell infiltration present in all levels of vagina (cranial, mid, and caudal) from all animals including sham controls based on post-study necropsy. The female reproductive tract from animals treated with the Ovaprene ring was comparable to the sham controls. The concentrations of serum iron in sheep treated with Ovaprene ring were similar compared to a sham treated animal. The average amount of ferrous gluconate released from Ovaprene over the 29-day period of use was 175 mg of the approximately 512 mg nominally loaded into the rings. CONCLUSIONS: Overall, the Ovaprene devices were well-tolerated in female sheep. IMPLICATIONS: This study should support a chronic (e.g., one year) contraceptive efficacy study in women.

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

PURPOSE: To evaluate long-term continuation rates, adverse events of ring pessary use at a minimum of 5 years follow-up, and factors associated with discontinuation in symptomatic pelvic organ prolapse (POP). METHODS: 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. RESULTS: During 12 year-period, 239 of 329 POP patients (72.6%) had successful fittings with ring pessary. The mean age was 67.8 ± 8.9 years (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 10 years, 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 70 years, 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. CONCLUSION: 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.

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

OBJECTIVE: Evaluate 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 DESIGN: Open-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. RESULTS: We 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. CONCLUSION: Use of Ovaprene resulted in meeting the prespecified criterion for contraceptive effect by all participants during all postcoital test cycles. IMPLICATIONS: The 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.

Risk factors for and outcomes of ring expulsions with a 1-year contraceptive vaginal system.

BACKGROUND: The US Food and Drug Administration-approved segesterone acetate and ethinyl estradiol ring-shaped contraceptive vaginal system, known as Annovera (Sever Pharma Solutions/QPharma, Malmö, Sweden), was inserted and removed under a woman's control for a 21 day in and 7 day out regimen for up to 13 cycles of use. OBJECTIVE: We aimed to describe the patterns of ring expulsion over time, to identify potential predictors of expulsion, and to evaluate the impact of expulsions on method discontinuation and pregnancy risk. STUDY DESIGN: Using data from 2064 participants who were enrolled in 2 multinational phase 3 clinical trials on the use of this contraceptive vaginal system, we examined data from participants' daily diaries for documentation of complete ring expulsion. We modeled the odds of reported expulsions over time with adjustment for background and demographic characteristics using mixed-effects logistic regression models with random intercepts. We compared the probability of continuation between those who did and those who did not report expulsions in the first cycle of use using survival analysis and hazards modeling. To determine if expulsions during the first cycle of use affected the risk for pregnancy, we calculated Pearl Indices. RESULTS: Most participants (75%) never experienced any expulsions during any cycle of use, and 91% to 97% did not experience an expulsion during any 1 cycle. The incidence of expulsion was highest in cycle 1 (9%). The odds of experiencing expulsions decreased by half in cycles 2 to 8 when compared with cycle 1 (0.48; 95% confidence interval, 0.40-0.58), and in cycles 9 to 13, expulsions were about a third of that in cycle 1 (0.32; 95% confidence interval, 0.26-0.41). Of those who did experience expulsions, most (62%-84%) experienced ≤2 expulsions per cycle. Participants from study sites in Latin America vs those in the United States had higher odds of not experiencing an expulsion (odds ratio, 1.95; 95% confidence interval, 1.45-2.63). Women with a higher education level had higher odds of experiencing an expulsion. Notably, parity, age, and body mass index were not associated with expulsion. Participants who experienced any expulsions in cycle 1 were more likely to discontinue use early (hazard ratio, 1.28; 95% confidence interval, 1.14-1.43) than participants who did not have an expulsion. The Pearl Index for participants who had expulsions during cycle 1 was 3.99 (95% confidence interval, 1.29-9.31), which was higher than that among participants who reported no expulsions (Pearl Index, 2.39; 95% confidence interval, 1.61-3.41), but the overlapping confidence intervals indicate that there is not sufficient evidence to demonstrate an association between expulsions and pregnancy risk. CONCLUSION: Expulsions were infrequent overall, decreased with subsequent cycles of use, and were not associated with body mass index or parity. Early discontinuation of product use was higher among participants who experienced an expulsion during cycle 1. Although it is unclear whether pregnancy risk was associated with expulsions, early recognition of expulsions among users may identify those at higher risk for discontinuation and may highlight when enhanced anticipatory counselling and guidance may be advantageous.

Acceptability of the dapivirine vaginal ring for HIV-1 prevention among women reporting engagement in transactional sex.

We assessed if acceptability of the dapivirine vaginal ring for HIV prevention differed among the subgroup of women who reported engaging in transactional sex prior to enrollment in MTN-020/ASPIRE (phase III trial in Malawi, South Africa, Uganda, and Zimbabwe, 2012-2015; n = 2629). Transactional sex was defined as receipt of money, goods, gifts, drugs, or shelter in exchange for sex in the past year. Dimensions of acceptability included: ease of use and physical sensation in situ, impacts on sex, partner's opinion, and likelihood of future use. We used Poisson regression models with robust standard errors to compare risk of acceptability challenges by baseline history of transactional sex. At product discontinuation, women exchanging sex found the ring comfortable (90%), easy to insert (92%) and nearly all (96%) were likely to use the ring in the future. Women who had exchanged sex were more likely to report feeling the ring during sex (ARR 1.43, 95% CI: 1.09, 1.89; p = 0.01) and slightly more likely to mind wearing the ring during menses (ARR 1.22, 95% CI: 1.01, 1,46; p = 0.04) and during sex (ARR 1.22, 95% CI: 1.02, 1.45; p = 0.03). Messaging and counseling should include enhanced support for use during sex and menses to support optimal use.

Women's motivations for participating in the dapivirine vaginal ring open label extension study.

Open-Label Extension (OLE) studies are important in the drug development process and are used to further support the licensing applications and regulatory approvals of products. We aimed to understand why women chose to join the HOPE OLE study - where women were offered the dapivirine vaginal ring after two pivotal trials were completed - through data collected from individual in-depth interviews. Ten women at each of the six HOPE research sites in Lilongwe, Malawi; Durban (2 sites) and Johannesburg, South Africa; Kampala, Uganda; and Chitungwiza, Zimbabwe, were enrolled (n = 60). Access to an effective user-initiated HIV prevention product was one of the main reasons women joined HOPE. Although many participants worried that their male partners might expose them to HIV, they chose to remain in their relationships and avoid conflict or confrontation with their partners by discreetly using the ring to protect themselves. Other reasons for joining were quality healthcare, reimbursement and altruism. Researchers should better understand social and personal motivators behind research participation in order to recognize community sociocultural norms and its influences on product acceptability and adherence challenges.

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.

Effect of a single dose of a combination injectable contraceptive for treatment of bothersome uterine bleeding in contraceptive implant(s) users: A randomized double-blind placebo-controlled trial.

OBJECTIVES: This study aimed to determine the proportion of participants whose uterine bleeding/spotting was interrupted for at least 7 days during the month after they received a combined hormonal injection. We also evaluated bleeding at 21 days and 12 weeks after the injection. STUDY DESIGN: We conducted a randomized, double-blind, placebo-controlled trial in 46 contraceptive implant users who presented with bothersome uterine bleeding/spotting. A single dose of a combination injectable contraceptive or placebo was administered intramuscularly at enrollment. RESULTS: The proportions of participants whose uterine bleeding/spotting was interrupted for at least 7 days the month after they received a combined hormonal injection were higher in the combination injectable contraception group than in the placebo group (87% vs 48%, p = 0.005). Participants who reported that they were bleeding free at 21 days after treatment were 52% and 35% in the combination injectable contraception group and placebo group, respectively (p = 0.24). At 12 weeks posttreatment, 17% of participants in the combination injectable contraception group and 4% in the placebo group reported cessation of bleeding with no recurrence (p = 0.34). The median days until the first bleeding interruption was shorter in the combination injectable contraception group compared with the placebo group (1 [interquartile range, 1-2] vs 8 [interquartile range, 1-28], p = 0.007). CONCLUSIONS: The combination injectable contraception interrupted bothersome uterine bleeding/spotting in contraceptive implant(s) users compared with placebo. However, this effect was limited only within the month when the treatment was administered. IMPLICATIONS: Bothersome uterine bleeding/spotting is a common side effect leading to contraceptive implant(s) discontinuation. In implant users experiencing these symptoms with no estrogen contraindications, a combined injectable contraception appears to rapidly improve bleeding for the duration of injectable exposure (1 month).

Assessing Per-Sex-Act HIV-1 Risk Reduction Among Women Using the Dapivirine Vaginal Ring.

BACKGROUND: Confounding introduced by individuals' sexual risk behavior is potentially a significant source of bias in HIV-1 prevention intervention studies. To more completely account for sexual behaviors when assessing the efficacy of the monthly dapivirine ring, a new longer-acting HIV-1 prevention option for women, we estimated per-sex-act risk reduction associated with product use. METHODS: We conducted a secondary analysis of data from MTN-020/ASPIRE, a phase 3, randomized, placebo-controlled efficacy trial of the dapivirine ring that recruited HIV-uninfected, African women aged 18-45 years. With cumulative sex acts as the time scale, we used multivariable Cox regression with inverse probability of censoring weights to estimate HIV-1 risk reduction associated with a rate of dapivirine release indicative of consistent product use. RESULTS: Women in the dapivirine ring group (n = 1187) had an estimated incidence rate of 2.3 (95% confidence interval [CI], 1.8-3.1) HIV-1 acquisition events per 10 000 sex acts versus 3.6 (95% CI, 2.9-4.4) per 10 000 acts in the placebo group (n = 1187). Dapivirine release indicative of consistent ring use was associated with a 63% (95% CI, 33%-80%) per-sex-act HIV-1 risk reduction. CONCLUSIONS: These results support the efficacy of the dapivirine vaginal ring for HIV-1 prevention and help to inform decision-making for women, providers, and policymakers regarding product use. CLINICAL TRIALS REGISTRATION: NCT01617096.

Brief Report: HIV Drug Resistance Assessment Among Women Who Seroconverted During the MTN-025/HOPE Open-Label Extension Dapivirine Vaginal Ring Trial.

BACKGROUND: Clinical trials of dapivirine (DPV) vaginal ring have shown it is safe, effective, and desired by women as an HIV prevention option. The risk of drug resistance is a potential concern for DPV ring users who acquire HIV. We conducted a comprehensive resistance evaluation of plasma samples from the women who seroconverted during the Microbicide Trials Network-025/HIV Open-label Prevention Extension (HOPE) study of DPV ring. METHODS: Plasma collected on the visit at which seroconversion was detected was tested by next-generation sequencing with unique molecular identifiers for non-nucleoside reverse transcriptase inhibitor (NNRTI) drug resistance mutations (DRM) present at ≥1% frequency. Bulk-cloned plasma-derived recombinant HIV was phenotyped in a TZM-bl-based assay for susceptibility to DPV and other NNRTI. HIV-1 RNA was retrospectively quantified in plasma samples collected before HIV seroconversion. RESULTS: Among 38 participants who seroconverted in HOPE, 7 (18%) had NNRTI DRM detected by next-generation sequencing with unique molecular identifiers including A98G, K103N, V106M, E138A, and V179D. Six of 7 samples with NNRTI DRM had <3-fold reduction in susceptibility to DPV. Only 1 sample with K103N and V179I polymorphism had 9-fold reduction in susceptibility to DPV, but this genotype occurred in an individual who did not use DPV ring, likely indicating transmitted resistance. Detection of NNRTI resistance was not higher in individuals who remained on DPV ring >3 months after acquiring HIV infection. CONCLUSIONS: NNRTI resistance among women who seroconverted during HOPE was infrequent and selection of DPV-specific mutations was not detected. DPV ring is considered a safe and effective option for HIV prevention in women.

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.

Physicochemical considerations in the formulation development of silicone elastomer vaginal rings releasing 5-nitroimidazole drugs for the treatment of bacterial vaginosis.

Bacterial vaginosis (BV) is a common dysbiosis of the human vaginal microbiota characterized by depletion of hydrogen peroxide and lactic acid-producing Lactobacillus bacteria and an overgrowth of certain facultative anaerobic bacteria. Although short-term cure rates following treatment with frontline antibiotics (most notably oral metronidazole (MNZ), clindamycin vaginal cream, and MNZ vaginal gel) are generally high, longer-term recurrence rates are an issue. The development of vaginal formulations offering continuous/sustained administration of antibiotic drugs over one or more weeks might prove useful in reducing recurrence. Here, we report the manufacture and preclinical testing of matrix-type vaginal rings offering sustained release of four 5-nitroimidazole antimicrobial drugs either being used clinically or having potential in treatment of BV - MNZ, tinidazole (TNZ), secnidazole (SNZ) and ornidazole (ONZ). All four drugs showed good compatibility with a medical-grade addition-cure silicone elastomer based upon thermal analysis experiments, and matrix-type rings containing 250 mg (3.125 %w/w) of each drug were successfully manufactured by reaction injection molding. 28-day in vitro drug release studies demonstrated root-time kinetics, with daily release rates of 25, 22, 9 and 6 mg/day½ for SNZ, ONZ, MNZ and TNZ, respectively. The rank order of drug release from rings correlated with the simple molecular permeability parameter S/V, where S is the measured drug solubility in silicone fluid and V is the drug molecular volume. The relative merits of SNZ and ONZ over MNZ (the current reference treatment) are discussed. The data support development of vaginal rings for sustained release of 5-nitroimidazole compounds for treatment of BV.

Online survey of consumer awareness and perceptions of a Massachusetts law for 12-month supply of contraception.

OBJECTIVES: This study aimed to characterize awareness of a 2017 Massachusetts (MA) law that ensures access to a 12-month supply of short-acting contraceptive methods (e.g., pill, patch, and vaginal ring) among short-acting contraceptive users in MA and to identify perceived benefits and concerns of a 12-month supply. STUDY DESIGN: An online survey was administered to a Qualtrics panel of MA women who were using short-acting contraceptive methods and were insured by an eligible health plan. The survey's primary outcome was general awareness of the law; interest in, receipt of, and perceived benefits and risks of a 12-month supply were also elicited. Analysis included descriptive statistics and bivariate and multivariable analyses examining factors associated with awareness of the law. RESULTS: Among the 207 survey respondents, 76% were aware of the law, and 93% expressed interest in receiving a 12-month supply of a short-acting method; however, only 9% received it. Respondents identified as White (66%), privately insured (59%), and pill users (44%). Concerns about a 12-month supply included privacy, product expiration, and change in personal medical status. Perceived benefits included avoiding multiple trips to pharmacy and increased compliance. Multivariable analyses showed general awareness of the law was only associated with employer-based insurance, with those respondents having 75% lower odds of being aware of the law than respondents with Medicaid coverage. CONCLUSION: Although a high percentage of women surveyed were aware of the law and most were interested in receiving a 12-month supply of their short-acting method, the low percentage who have received a 12-month supply suggests barriers to policy uptake. IMPLICATIONS: This study describes perceptions of the 12-month supply provision of the contraception Act Advancing Contraceptive Coverage and Economic Security in our State law. Addressing consumer concerns may be important to improve the implementation and dissemination of this state policy change.

Adolescent Girls and Young Women's Experiences with Disclosing Oral PrEP or Dapivirine Vaginal Ring Use: a Multi-Country Qualitative Analysis.

Effective use of oral pre-exposure prophylaxis (PrEP) has been low among adolescent girls and young women (AGYW) in Eastern and Southern Africa, partly due to stigma and opposition from key influencers. Understanding AGYW's experiences of disclosure of different PrEP modalities to key influencers may inform strategies to motivate uptake and adherence. We analyzed qualitative in-depth interviews and focus group discussions data from 119 participants in the MTN-034/REACH (Reversing the Epidemic in Africa with Choices in HIV Prevention) study of oral PrEP and the dapivirine vaginal ring (ring) to explore AGYW's disclosure experiences. We found that AGYW disclosure experiences varied across influencers and product type. The ring was disclosed less often to most influencers, except partners, because it was discreet. Oral PrEP was disclosed more often, because pills were more common and to avoid HIV stigma given that oral PrEP resembled HIV treatment. Ultimately, disclosure typically led most key influencers to support product use through reminders and encouragement. While disclosure yielded positive support from influencers, further community awareness of both PrEP products is essential to reduce potential opposition and perceived stigma.Clinical Trial Number: NCT03593655.

Acceptability and Use of the Dapivirine Vaginal Ring and Daily Oral Pre-exposure Prophylaxis (PrEP) During Breastfeeding in South Africa, Malawi, Zimbabwe, and Uganda.

This study examines qualitative acceptability of the dapivirine vaginal ring (DVR) and oral daily pre-exposure prophylaxis (PrEP) among breastfeeding persons participating in Microbicide Trials Network 043/B-PROTECTED, a phase 3B safety and drug detectability study of DVR and oral PrEP in breastfeeding. A subsample of 52 participants were purposively sampled to participate in an in-depth interview (IDI). Breastfeeding participants found both study products to be acceptable, and easy to use. A common motivation for product use was to protect the baby from HIV, although participants' understanding of how the study drug would work to protect their babies was often unclear. While most participants did not report experiencing side effects, fears about side effects were common as both initial worries about how the study products would affect their health and the health of their baby, and increased anxiety that health issues experienced by them, or their baby were from the products.

The impact of combined contraceptive vaginal ring on vaginal environment: an observational, longitudinal study.

PURPOSE: To assess the relationship between combined contraceptive vaginal ring (CVR) and vaginal microbiome using 16S rRNA gene sequencing. MATERIALS AND METHODS: We enrolled 20 women for 8 weeks in an open-label study using CVR (NuvaRing®) that delivered 15 mcg ethinylestradiol and 120 mcg etonogestrel daily. The vaginal microbiome was assessed at baseline and after 2 months by sequencing the 16S rRNA genes amplified from the total genomic DNA isolated from the sample. RESULTS: Bacterial distribution richness and equity did not significantly change after 2 months, and the dominant bacterial strain was Lactobacillus crispatus. Only one woman with a history of vestibulodynia and recurrent vulvovaginitis showed an increase in bacterial biodiversity, with a switch to the relative abundance of anaerobic bacteria. CONCLUSIONS: Our results suggest that CVR does not adversely affect the composition and structure of the vaginal microbiome. However, special care should be taken in patients with a history of vestibulodynia and/or recurrent vulvovaginal infections.

Contraceptive vaginal ring does not adversely affect vaginal microbiome except in the case of recurrent vulvovaginal infections or vestibulodynia.

Satisfaction with a Segesterone Acetate and Ethinyl Estradiol Contraceptive Vaginal System Among Recent Oral Contraceptive or Hormonal Contraceptive Vaginal Ring Users.

Background: We evaluated satisfaction with use of a segesterone acetate and ethinyl estradiol (0.15/0.013 mg) contraceptive vaginal system (CVS) among women who had recently used a monthly contraceptive vaginal ring or contraceptive pills. The CVS is a ring-shaped device used in a 21-days-in/7-days-out regimen for 13 cycles. Materials and Methods: We analyzed post hoc satisfaction responses at cycle 3 and end of study (EOS) from a subset of participants with documented recent use of the monthly ring or daily pills before enrollment in a multinational, phase 3, 13-cycle trial evaluating the CVS. EOS included results from participants who had completed ≥10 cycles. Results were summarized descriptively. Results: We identified 128 recent ring and 219 recent pill users at cycle 3 (of 1033 survey participants), and 92 and 148, respectively, at EOS (of 622 survey participants); overall satisfaction with CVS use was high (≥90%). At EOS, most ring (89%) and pill (97%) users liked the CVS as much/better than any previous method. The two most-liked CVS features included ease of use and 1-year duration; the two most disliked features included ring insertion and feeling it coming out. At EOS, ≥88% of both groups reported no concern about using the same CVS for a year, and most (>80%) had recommended it to friends or family members. Conclusion: The CVS clinical trial participants who were recent ring/pill users reported high satisfaction and liked it as much/better than any previously used contraceptive; the CVS may be a good contraceptive option for switchers. Clinical trial registration NCT00263341.

ZB-06, a vaginal film containing an engineered human contraceptive antibody (HC4-N), demonstrates safety and efficacy in a phase 1 postcoital test and safety study.

BACKGROUND: With an unplanned pregnancy rate of 50% or more in many countries, there is an urgent need for contraceptives that are more accessible and acceptable. To meet the growing demand for new contraceptives, ZabBio developed ZB-06, a vaginal film containing HC4-N, a human contraceptive antibody that inactivates sperm. OBJECTIVE: This study aimed to assess the potential contraceptive activity of the ZB-06 film using a surrogate assessment for contraceptive efficacy, the postcoital test. We also assessed clinical safety of film use among healthy heterosexual couples. Serum, cervical mucus, and vaginal fluid HC4-N antibody concentrations and sperm agglutination potency were determined after single film use. Changes in the concentration of soluble proinflammatory cytokines and vaginal Nugent score after film use were measured as subclinical safety endpoints. STUDY DESIGN: This was a phase 1, first-in-woman, open-label, proof-of-concept, postcoital test and safety study. RESULTS: A total of 20 healthy women were enrolled in the study, and 8 heterosexual couples completed all study visits. The product was safe for both female participants and their male sexual partners. The postcoital test performed on ovulatory cervical mucus at baseline (no product use) revealed a mean of 25.9 (±30.6) progressively motile sperm per high-power field. After use of a single ZB-06 film before intercourse, this number dropped to 0.04 (±0.06) progressively motile sperm per high-power field (P<.0001). At the follow-up postcoital test visit approximately 1 month later (no product use), a mean of 47.4 (±37.4) progressively motile sperm per high-power field was observed, indicating contraceptive reversibility. CONCLUSION: A single dose of the ZB-06 film applied before intercourse was safe and met efficacy surrogate benchmarks of excluding progressively motile sperm from ovulatory cervical mucus. These data indicate that ZB-06 is a viable contraceptive candidate warranting further development and testing.

Defining principles for a choice-based approach to HIV prevention.

The HIV prevention landscape is on the cusp of an unprecedented era of multiple biomedical prevention products available for distribution. Several HIV prevention options, such as oral pre-exposure prophylaxis (PrEP), dapivirine vaginal rings, and injectable cabotegravir for PrEP, are becoming more widely available. Although the future HIV prevention market promises to be rich in options, it would benefit from a core set of principles that uphold choice in all phases of product development, assessment, and introduction. These principles, as presented in this Viewpoint, show the applicability, opportunities, and challenges of choice in different contexts of HIV prevention and provide checkpoints of accountability. By committing to these principles, stakeholders at national and global levels can advance choice across all phases of the HIV prevention market, thereby ensuring that individuals can realise their right to choose when and how to prevent HIV in their own lives.