Women Want Choices: Opinions from the Share.Learn.Shape Global Internet Survey About Multipurpose Prevention Technology (MPT) Products in Development.

Women need multipurpose prevention technologies (MPTs) to simultaneously prevent sexually transmitted infections (STIs), including HIV, with or without contraception. User feedback early in product development is critical for maximizing uptake and continuation. Our global online survey (April 2017-December 2018) explored women's opinions about MPT formulations in development (e.g., fast-dissolving vaginal inserts, vaginal films, intravaginal rings, injectables, implants), preferences for long-acting or "on-demand" methods, and interest in a contraceptive MPT versus products for HIV/STI prevention alone. Of the 630 women in our final analysis (mean 30 years old; range 18-49), 68% were monogamous, 79% completed secondary education, 58% had ≥ 1 child, 56% were from sub-Saharan Africa and 82% preferred a cMPT versus HIV/STI prevention alone. There were no clear preferences for any specific product or product type (long-acting, on-demand, daily). No single product will appeal everyone, however, adding contraception is likely to increase uptake of HIV/STI prevention methods for most women.

RESUMEN: Las mujeres necesitan tecnologías de prevención multipropósito (TPM) para prevenir simultáneamente las infecciones de transmisión sexual (ITS), incluido el VIH, con o sin anticoncepción. Las opiniones de los usuarios cuando un producto comienza a desarrollarse son fundamentales para maximizar la adopción y continuación de dicho producto. Nuestra encuesta global realizada en internet (abril de 2017­diciembre de 2018) exploró las opiniones de las mujeres sobre diferentes fórmulas o dispositivos de TPM que se están desarrollando (ej., insertos vaginales de disolución rápida, láminas vaginales, anillos intravaginales, inyectables, implantes). En esta encuesta se indagó acerca de las preferencias en términos de período de acción (prolongado o breve) y propósito del uso (anticonceptivo, productos para la prevención del VIH/ITS, o ambos). De las 630 mujeres (media de 30 años; rango 18­49) en el análisis final, el 68% eran monógamas, el 79% completaron la educación secundaria, el 58% tenían ≥ 1 hijo, el 56% eran del África subsahariana y el 82% preferían una TPM con componente anticonceptivo en vez de un producto para la prevención de VIH/ITS exclusivamente. No hubo preferencias claras por ningún producto o tipo de producto específico (de acción prolongada, de acción breve, de uso diario). Ningún producto por sí solo logró abarcar todas las preferencias; sin embargo, es probable que la inclusión de métodos anticonceptivos en una TPM aumente el uso de métodos de prevención del VIH/ITS en la mayoría de las mujeres.

Estradiol inhibits HIV-1BaL infection and induces CFL1 expression in peripheral blood mononuclear cells and endocervical mucosa.

An inhibitory effect of estradiol (E2) on HIV-1 infection was suggested by several reports. We previously identified increased gene expression of actin-binding protein cofilin 1 (CFL1) in endocervix in the E2-dominated proliferative phase of the menstrual cycle. Actin cytoskeleton has an integral role in establishing and spreading HIV-1 infection. Herein, we studied in vitro effects of E2 on HIV-1 infection and on CFL1 expression to gain insight into the mechanism of HIV-1 inhibition by E2. E2 dose-dependently inhibited HIV-1BaL infection in peripheral blood mononuclear cells (PBMCs) and endocervix. In PBMCs and endocervix, E2 increased protein expression of total CFL1 and phosphorylated CFL1 (pCFL1) and pCFL1/CFL1 ratios. LIMKi3, a LIM kinase 1 and 2 inhibitor, abrogated the phenotype and restored infection in both PBMCs and endocervix; inhibited E2-induced expression of total CFL1, pCFL1; and decreased pCFL1/CFL1 ratios. Knockdown of CFL1 in PBMCs also abrogated the phenotype and partially restored infection. Additional analysis of soluble mediators revealed decreased concentrations of pro-inflammatory chemokines CXCL10 and CCL5 in infected tissues incubated with E2. Our results suggest a link between E2-mediated anti-HIV-1 activity and expression of CFL1 in PBMCs and endocervical mucosa. The data support exploration of cytoskeletal signaling pathway targets for the development of prevention strategies against HIV-1.

Impact on hepatic estrogen-sensitive proteins by a 1-year contraceptive vaginal ring delivering Nestorone® and ethinyl estradiol.

OBJECTIVES: Estrogen-sensitive hepatic proteins were assessed in women using a contraceptive vaginal ring (CVR) delivering 150mcg Nestorone® (NES) and 15mcg ethinyl estradiol (EE). STUDY DESIGN: A substudy of the Contraceptive Clinical Trials Network of the National Institute of Child Health and Human Development enrolled 129 participants, with assessments of factor VIII, fibrinogen, protein S (PS) and sex hormone binding globulin (SHBG). Thirty-six participants had used combined hormonal contraceptives (CHCs) in the cycle preceding first CVR use (recent users) and 70 had no history of recent use (nonusers). RESULTS: Mean values at baseline were within the normal range for all four proteins but were higher for factor VIII, fibrinogen and SHBG and significantly lower for PS in recent compared to nonusers. During NES/EE CVR use, factor VIII, fibrinogen and PS were within the normal range; however, SHBG levels were increased by nearly 100% at Cycle 13. The change from baseline to final evaluation was statistically significant for all proteins in nonusers. The change in recent users was significant for factor VIII at Cycle 6 and for SHBG at Cycles 6 and 13, but not for PS or fibrinogen. CONCLUSION: NES/EE CVR for up to 13cycles was associated with changes from baseline in plasma levels of factor VIII, fibrinogen and PS that were within the normal range, with SHBG levels above the normal range by Cycle 6. Nonusers of CHC before CVR showed wider changes in values versus recent users whose baseline values were increased by previous EE exposure. IMPLICATIONS: Recent use of CHCs demonstrated significant changes in all four measured hepatic proteins at baseline compared to nonusers. Use of the NES/EE CVR further changed these hepatic protein markers, but values remained within the normal range. Prebaseline exposure to estrogen can obscure interpretation of hepatic proteins changes associated with a second CHC.