Multi-morbidity and Highly Effective Contraception in Reproductive-Age Women in the US Intermountain West: a Retrospective Cohort Study.

BACKGROUND: Women with chronic health conditions benefit from reproductive planning and access to highly effective contraception. OBJECTIVE: To determine the prevalence of and relationship between chronic health conditions and use of highly effective contraception among reproductive-age women. DESIGN: Retrospective cohort study using electronic health records. PARTICIPANTS: We identified all women 16-49 years who accessed care in the two largest health systems in the US Intermountain West between January 2010 and December 2014. MAIN MEASURES: We employed administrative codes to identify highly effective contraception and flag chronic health conditions listed in the US Medical Eligibility Criteria for Contraceptive Use (US MEC) and known to increase risk of adverse pregnancy outcomes. We described use of highly effective contraception by demographics and chronic conditions. We used multinomial logistic regression to relate demographic and disease status to contraceptive use. KEY RESULTS: Of 741,612 women assessed, 32.4% had at least one chronic health condition and 7.3% had two or more chronic conditions. Overall, 7.6% of women with a chronic health condition used highly effective contraception vs. 5.1% of women without a chronic condition. Women with chronic conditions were more likely to rely on public health insurance. The proportion of women using long-acting reversible contraception did not increase with chronic condition number (5.8% with 1 condition vs. 3.2% with 5 or more). In regression models adjusted for age, race, ethnicity, and payer, women with chronic conditions were more likely than those without chronic conditions to use highly effective contraception (aRR 1.4; 95% CI 1.4-1.5). Public insurance coverage was associated with both use of long-acting reversible contraception (aRR 2.2; 95% CI 2.1-2.3) and permanent contraception (aRR 2.9; 95% CI 2.7-3.1). CONCLUSIONS: Nearly a third of reproductive-age women in a regional health system have one or more chronic health condition. Public insurance increases the likelihood that women with a chronic health condition use highly effective contraception.

Engineering a degradable polyurethane intravaginal ring for sustained delivery of dapivirine.

We describe the engineering of a degradable intravaginal ring (IVR) for the delivery of the potent HIV-1 reverse transcriptase inhibitor dapivirine. The degradable polymer used in fabricating the device incorporated poly(caprolactone) ester blocks in a poly(tetramethylene ether) glycol ABA type polyurethane backbone. The polymer was designed to maintain its structure for 1 month during usage and then degrade in the environment post-disposal. In vitro release of dapivirine showed zero-order kinetics for up to 1 month and significant levels of drug release into engineered vaginal tissue. The mechanical properties of the degradable IVR were comparable to those of a widely used contraceptive intravaginal ring upon exposure to simulated vaginal conditions. Incubation under simulated vaginal conditions for a month caused minimal degradation with minimal effect on the mechanical properties of the ring and polymer. The cytotoxicity evaluation of the drug-loaded IVRs against Vk2/E6E7 human vaginal epithelial cells, Lactobacillus jensenii, and engineered vaginal tissue constructs showed the degradable polyurethane to be non-toxic. In vitro evaluation of inflammatory potential monitored through the levels of inflammatory cytokines IL-8, IL-1α, IL-6, IL-1ß, and MIP-3α when engineered EpiVaginal™ tissue was incubated with the polyurethanes suggested that the degradable polyurethane was comparable to commercial medical grade polyurethane. These results are encouraging for further development of this degradable IVR for topical vaginal delivery of microbicides.

Polyurethane intravaginal ring for controlled delivery of dapivirine, a nonnucleoside reverse transcriptase inhibitor of HIV-1.

Women-controlled methods for prevention of male-to-female sexual transmission of HIV-1 are urgently needed. Providing inhibitory concentrations of HIV-1 reverse transcriptase inhibitors to impede the replication of the virus in the female genital tissue offers a mechanism for prophylaxis of HIV-1. To this end, an intravaginal ring device that can provide long duration delivery of dapivirine, a nonnucleoside reverse transcriptase inhibitor of HIV-1, was developed utilizing a medical-grade polyether urethane. Monolithic intravaginal rings were fabricated and sustained release with cumulative flux linear with time was demonstrated under sink conditions for a period of 30 days. The release rate was directly proportional to the amount of drug loaded. Another release study conducted for a week utilizing liposome dispersions as sink conditions, to mimic the partitioning of dapivirine into vaginal tissue, also demonstrated release rates constant with time. These results qualify polyether urethanes for development of intravaginal rings for sustained delivery of microbicidal agents.