Dominika Seidman

Integrating Preexposure Prophylaxis for Human Immunodeficiency Virus Prevention Into Womenʼs Health Care in the United States

Women comprise one in five new human immunodeficiency virus (HIV) diagnoses in the United States. Trials and implementation projects demonstrate preexposure prophylaxis for HIV prevention is effective in women. Preexposure prophylaxis is a method of preventing HIV acquisition by having an HIV-negative individual take antiretroviral medication before exposure. The U.S. Food and Drug Administration approved daily oral tenofovir disoproxil fumarate coformulated with emtricitabine as preexposure prophylaxis for HIV prevention in 2012. Preexposure prophylaxis is highly dependent on adherence for effectiveness. The Centers for Disease Control and Prevention recommends offering preexposure prophylaxis to individuals at significant risk of infection and estimates 468,000 women in the United States are eligible for preexposure prophylaxis. Although variable individual and structural forces affect each womans medication adherence, and therefore the effectiveness of preexposure prophylaxis, womens health care providers are uniquely positioned to screen, counsel about, and offer preexposure prophylaxis. Shared decision-making provides a framework for these clinical encounters, allowing patients and clinicians to make health care decisions together based on scientific evidence and patient experiences. By incorporating fertility desires and contraceptive needs, health care providers effectively integrate sexual and reproductive health care. Including preexposure prophylaxis in womens health services requires health care provider training and attention to lessons learned from family planning and HIV prevention. Nevertheless, obstetrician-gynecologists have an opportunity to play a critical role in reducing sexual transmission of HIV in the United States by integrating preexposure prophylaxis education and provision into their practices.

Contraceptive use and pregnancy intentions among transgender men presenting to a clinic for sex workers and their families in San Francisco.

PURPOSE Although many transgender men may be able to conceive, their reproductive health needs are understudied. METHODS We retrospectively reviewed charts of transgender men presenting to a clinic for sex workers to describe the proportion at risk for pregnancy, pregnancy intentions, and contraceptive use. RESULTS Of 26 transgender men identified, half were at risk for pregnancy. Most desired to avoid pregnancy but used only condoms or no contraception. Two individuals desired pregnancy, were taking testosterone (a teratogen), and not using contraception. CONCLUSION Further research is needed to explore how to best provide family planning services including preconception and contraception care to transgender men.

Changes in care associated with the introduction of a postpartum hemorrhage patient safety program.

OBJECTIVE To determine whether the introduction of a postpartum hemorrhage (PPH) patient safety program was associated with changes in patient care or outcomes. STUDY DESIGN A multipronged patient safety program regarding PPH was instituted at a tertiary care maternity hospital. Patient care and outcomes were assessed for 6 months prior to (period A) and 6 months after (period B) program institution. RESULTS In all, 278 and 341 women were diagnosed with PPH during periods A and B, respectively. Women who had a PPH after the program were more likely to receive more than one dose of prostaglandin F2 α (24% versus 9%, p = 0.01) and more than one type of uterotonic (34% versus 25%, p = 0.02) and to have a B-lynch suture placed (9.4% versus 4.7%, p = 0.03). The frequency of blood transfusion, hysterectomy, and intensive care unit admission were similar between periods. CONCLUSION Introduction of a PPH safety program resulted in several indications of a more quickly escalated response.

Effects of depot-medroxyprogesterone acetate on the immune microenvironment of the human cervix and endometrium: implications for HIV susceptibility

Depot-medroxyprogesterone acetate is a commonly used injectable contraceptive that has been associated with an increased risk of HIV acquisition. This study compares effects of depot-medroxyprogesterone acetate on immune parameters from several upper reproductive tract compartments relevant to HIV-1 susceptibility in repetitive samples from 15 depot-medroxyprogesterone acetate users and 27 women not on hormonal contraceptives. Compared with samples from unexposed women in the mid-luteal phase, depot-medroxyprogesterone acetate use was associated with: increased endocervical concentrations of MCP1 and IFNalpha2; decreased endocervical concentrations of IL1beta and IL6; increased proportions of endometrial CD4+ and CD8+ cells expressing the activation marker HLADR; increased density of endometrial macrophages; and decreased density of endometrial regulatory T cells. Unlike previous reports with samples from the vagina, we did not observe increased expression of the HIV co-receptor CCR5 on CD4+ T cells in the endocervix or endometrium. Our results indicate important differences in anatomic compartments regarding mechanisms by which depot-medroxyprogesterone acetate could be associated with increased risk of HIV acquisition, including increased recruitment of macrophages to the endometrium, decreased levels of pro-inflammatory cytokines in the endocervix possibly leading to enhanced susceptibility to viral infection, and activation of endometrial T cells.

Integrase inhibitors in late pregnancy and rapid HIV viral load reduction

BACKGROUND Minimizing time to HIV viral suppression is critical in pregnancy. Integrase strand transfer inhibitors (INSTIs), like raltegravir, are known to rapidly suppress plasma HIV RNA in nonpregnant adults. There are limited data in pregnant women. OBJECTIVE We describe time to clinically relevant reduction in HIV RNA in pregnant women using INSTI-containing and non-INSTI-containing antiretroviral therapy (ART) options. STUDY DESIGN We conducted a retrospective cohort study of pregnant HIV-infected women in the United States from 2009 through 2015. We included women who initiated ART, intensified their regimen, or switched to a new regimen due to detectable viremia (HIV RNA >40 copies/mL) at ≥20 weeks gestation. Among women with a baseline HIV RNA permitting 1-log reduction, we estimated time to 1-log RNA reduction using the Kaplan-Meier estimator comparing women starting/adding an INSTI in their regimen vs other ART. To compare groups with similar follow-up time, we also conducted a subgroup analysis limited to women with ≤14 days between baseline and follow-up RNA data. RESULTS This study describes 101 HIV-infected pregnant women from 11 US clinics. In all, 75% (76/101) of women were not taking ART at baseline; 24 were taking non-INSTI containing ART, and 1 received zidovudine monotherapy. In all, 39% (39/101) of women started an INSTI-containing regimen or added an INSTI to their ART regimen. Among 90 women with a baseline HIV RNA permitting 1-log reduction, the median time to 1-log RNA reduction was 8 days (interquartile range [IQR], 7-14) in the INSTI group vs 35 days (IQR, 20-53) in the non-INSTI ART group (P < .01). In a subgroup of 39 women with first and last RNA measurements ≤14 days apart, median time to 1-log reduction was 7 days (IQR, 6-10) in the INSTI group vs 11 days (IQR, 10-14) in the non-INSTI group (P < .01). CONCLUSION ART that includes INSTIs appears to induce more rapid viral suppression than other ART regimens in pregnancy. Inclusion of an INSTI may play a role in optimal reduction of HIV RNA for HIV-infected pregnant women presenting late to care or failing initial therapy. Larger studies are urgently needed to assess the safety and effectiveness of this approach.

Intravaginal practices among HIV-negative female sex workers along the US-Mexico border and their implications for emerging HIV prevention interventions

To describe intravaginal practices (IVPs) among female sex workers (FSWs) who inject drugs in two cities—Tijuana and Ciudad Juarez—on the border between the USA and Mexico.

Effects of the levonorgestrel-releasing intrauterine device on the immune microenvironment of the human cervix and endometrium.

There is little information regarding the impact of the intrauterine device on immune parameters of the upper female reproductive tract related to risk of HIV acquisition.

Smoking, HIV, and risk of pregnancy loss

Objective:Cigarette smoking during pregnancy increases risks of poor pregnancy outcomes including miscarriage and stillbirth (pregnancy loss), but the effect of smoking on pregnancy loss among HIV-infected women has not been explored. Here, investigated the impact of smoking on risk of pregnancy loss among HIV-positive and HIV-negative women, and estimated the potential impact of realistic smoking cessation interventions on risk of pregnancy loss among HIV-positive women. Design:We analyzed pregnancy outcomes in HIV-positive and HIV-negative participants in the Womens Interagency HIV Study between 1994 and 2014. Methods:We estimated effects of current smoking at or immediately before pregnancy on pregnancy loss; we controlled for confounding using regression approaches, and estimated potential impact of realistic smoking cessation interventions using a semiparametric g-formula approach. Results:Analysis examined 1033 pregnancies among 659 women. The effect of smoking on pregnancy loss differed dramatically by HIV status: adjusted for confounding, the risk difference comparing current smokers to current nonsmokers was 19.2% (95% confidence limit 10.9–27.5%) in HIV-positive women and 9.7% (95% confidence limit 0.0–19.4%) in HIV-negative women. These results were robust to sensitivity analyses. We estimated that we would need to offer a realistic smoking cessation intervention to 36 women to prevent one pregnancy loss. Conclusion:Smoking is a highly prevalent exposure with important consequences for pregnancy in HIV-positive pregnant women in the United States, even in the presence of potent highly active antiretroviral therapy. This evidence supports greater efforts to promote smoking cessation interventions among HIV-positive women, especially those who desire to become pregnant.

Emerging Technologies to Prevent Pregnancy and Sexually Transmitted Infections in Women.

Worldwide, there continues to be a large unmet need for family planning and sexually transmitted infection (STI) prevention methods. Multipurpose prevention technology (MPT) is a general term encompassing any single prevention methodology targeting more than one STI (including HIV) and/or pregnancy. While innovation has been slow over the past several decades, recent scientific advances have resulted in new products entering clinical trials. This review focuses primarily on multipurpose technologies that are designed to prevent pregnancy and HIV. To examine the current state of MPTs, we outline key discoveries of biologic mechanisms that influence susceptibility of the female genital tract to HIV and STIs, and review the effects of hormonal contraception on HIV susceptibility. We discuss the state of currently available HIV prevention strategies for women, and their interactions with hormonal contraceptive products. Finally, we describe MPTs currently in preclinical and clinical trials and propose ongoing questions requiring research to help advance the field.

The FACTS about women and pre-exposure prophylaxis

The Editorial in the April issue, Antiretroival gels: facing the FACTS, describes the HIV community’s collective disappointment regarding the FACTS trial’s negative results. However, the conclusions that gels are not “practically feasible” and vaginal rings may be the “usable prevention strategy” that women need is misguided. Oral pre-exposure prophylaxis (PrEP) is more promising than ever for women: the HPTN 067 ADAPT trial and Partners PrEP Demonstration Project, both presented at the same conference as FACTS, confirmed that women want HIV prevention methods and adhere to daily oral dosing, especially when openlabel products known to be eff ective are used. What is needed next is diversifi cation of prevention methods and implementation strategies responsive to the contexts of women’s lives. Why did women in FACTS and some other HIV prevention trials not use study drugs? Research with unproven products, placebo arms, and blinding coupled with stigma around PrEP use may contribute. An ecological model of social determinants of health provides additional explanations. When considering the individual, social, cultural, economic and environmental factors that eff ect a woman’s risk of HIV, a simple switch from gels to rings cannot circumvent the powerful forces at play. No single intervention can take on the complex factors leading women to disproportionately carry the HIV burden in sub-Saharan Africa. Rather, various prevention choices and multipronged interventions addressing social determinants are needed to promote every woman’s agency in managing her sexual and reproductive health.