Unique Profile of Inflammation and Immune Activation in Pregnant People With HIV in the United States.

BACKGROUND: Little is known about inflammation/immune activation during pregnancy in people with HIV (PWH) and growth in their children who are HIV-exposed and uninfected (CHEU). METHODS: Using data from the Pediatric HIV/AIDS Cohort Study and an HIV-seronegative comparison group, we assessed associations of (1) HIV status, mode of HIV acquisition (perinatally vs nonperinatally acquired), and type of antiretroviral therapy (ART) with inflammation/immune activation in pregnancy; and (2) inflammation/immune activation in pregnancy with growth of CHEU at 12 months. Interleukin 6 (IL-6), high-sensitivity C-reactive protein (hs-CRP), soluble(s) TNF-α receptor 1 and 2 (sTNFR1, sTNFR2), sCD14, and sCD163 were measured between 13 and 27 weeks' gestation. Linear regression models were fit to estimate differences between groups for each log-transformed biomarker, adjusted for confounders. RESULTS: Pregnant PWH (188 total, 39 perinatally acquired, 149 nonperinatally acquired) and 76 HIV-seronegative persons were included. PWH had higher IL-6, sTNFR1, sCD14, and sCD163 and lower sTNFR2 compared to HIV-seronegative persons in adjusted models. Among PWH, sCD163 was higher in those with perinatally versus nonperinatally acquired HIV and on PI-based versus INSTI-based ART. Higher maternal concentrations of IL-6, sTNFR2, and hs-CRP were associated with poorer growth at 12 months. CONCLUSIONS: Maternal HIV status is associated with a distinct profile of inflammation/immune activation during pregnancy, which may influence child growth.

Bone, Brain, Heart study protocol: A resilient nested, tripartite prospective cohort study of the role of estrogen depletion on HIV pathology.

PURPOSE: We describe the rationale for and design of an innovative, nested, tripartite prospective observational cohort study examining whether relative estrogen insufficiency-induced inflammation amplifies HIV-induced inflammation to cause end organ damage and worsen age-related co-morbidities affecting the neuro-hypothalamic-pituitary-adrenal axis (Brain), skeletal (Bone), and cardiovascular (Heart/vessels) organ systems (BBH Study). METHODS: The BBH parent study is the Multicenter AIDS Cohort/Women's Interagency HIV Study Combined Cohort Study (MWCCS) with participants drawn from the Atlanta MWCCS site. BBH will enroll a single cohort of n = 120 women living with HIV and n = 60 HIV-negative women, equally distributed by menopausal status. The innovative multipart nested study design of BBH, which draws on data collected by the parent study, efficiently leverages resources for maximum research impact and requires extensive oversight and management in addition to careful implementation. The presence of strong infrastructure minimized BBH study disruptions due to changes in the parent study and the COVID-19 pandemic. CONCLUSION: BBH is poised to provide insight into sex and HIV associations with the neuro-hypothalamic-pituitary-adrenal axis, skeletal, and cardiovascular systems despite several major, unexpected challenges.

Interest in and Uptake of Postabortion Long-Acting Reversible Contraception After Counseling at a Free-Standing Abortion Care Ambulatory Surgery Center, Atlanta, Georgia, 2017‒2018.

We sought to determine the impact of brief previsit counseling on long-acting reversible contraception (LARC) interest and uptake immediately after abortion. We conducted a randomized controlled trial at a free-standing abortion care ambulatory surgery center in metro-Atlanta, Georgia (2017-2018). Among 1270 women, a brief previsit counseling intervention increased interest in LARC by 4.5 percentage points, and interest in LARC after the intervention increased uptake by 9.6 percentage points. Providing brief previsit counseling significantly increased postabortion LARC uptake. (Am J Public Health. 2022;112(9):1257-1260. https://doi.org/10.2105/AJPH.2022.306940).

Sexually Transmitted Infections in Pregnant People With Human Immunodeficiency Virus: Temporal Trends, Demographic Correlates, and Association With Preterm Birth.

BACKGROUND: We describe trends in prevalence and identify factors associated with Chlamydia trachomatis (CT), Neisseria gonorrhoeae (NG), syphilis, and Trichomonas vaginalis (TV) diagnosed in pregnancy among US people with human immunodeficiency virus (PWH) and evaluate associations of sexually transmitted infections (STIs) with preterm birth (PTB). METHODS: We included pregnant PWH enrolled in the Surveillance Monitoring for ART Toxicities dynamic cohort of the Pediatric HIV/AIDS Cohort Study network who delivered between 2010 and 2019. Multivariable log-binomial or Poisson generalized estimating equation models were used to estimate the association of calendar year with each STI, controlling for confounders; the association of demographic and clinical factors with each STI; and the association of each STI with PTB. RESULTS: The sample included 2241 pregnancies among 1821 PWH. Median age at delivery was 29.2 years; 71% of participants identified as Black or African American. STI prevalence was: CT 7.7%, NG 2.3%, syphilis 2.4%, and TV 14.5%; 30% had unknown TV status. There were no temporal changes in STI prevalence. Younger age and initial HIV viral load ≥400 copies/mL were associated with increased risk of CT, NG, and TV. Recreational substance use was a risk factor for NG, syphilis, and TV. No STI was associated with PTB. CONCLUSIONS: Unlike nationwide trends, no changes in STI prevalence during the study period were observed. The large proportion with unknown TV status underscores the need for increased adherence to screening guidelines. STIs diagnosed during pregnancy in PWH were not associated with risk of PTB.

Marijuana, Opioid, and Alcohol Use Among Pregnant and Postpartum Individuals Living With HIV in the US.

Importance: Amid the opioid epidemic and evolving legal and social changes with marijuana, little is known about substance use among pregnant and postpartum people living with HIV. Objectives: To evaluate trends in marijuana, alcohol, and opioid use during pregnancy and the first year postpartum among US people living with HIV and the differences in substance use based on marijuana legalization status. Design, Setting, and Participants: Data from the Surveillance Monitoring for Antiretroviral Toxicities (SMARTT) study of the Pediatric HIV/AIDS Cohort Study were analyzed. SMARTT-enrolled, pregnant people living with HIV at 22 US sites from January 1, 2007, to July 1, 2019, with self-reported substance use data available in pregnancy, 1 year postpartum, or both were assessed. Exposures: Calendar year and state marijuana legalization status. Main Outcomes and Measures: The prevalence of any use of each of the following substances was calculated by calendar year, separately for pregnancy and postpartum: marijuana, alcohol, opioid, and concomitant alcohol and marijuana. Log binomial models were fit using general estimating equations to evaluate the mean annual change, accounting for repeat pregnancies. The study also evaluated differences in substance use by state recreational or medical marijuana legalization status. Results: Substance use data were available for 2926 pregnancies from 2310 people living with HIV (mean [SD] age, 28.8 [6.1] years; 822 [28.1%] Hispanic, 1859 [63.5%] non-Hispanic Black, 185 [6.3%] White, 24 [0.8%] of more than 1 race, 24 [0.8%] of other race or ethnicity [individuals who identified as American Indian, Asian, or Native Hawaiian or other Pacific Islander], and 12 [0.4%] with unknown or unreported race or ethnicity). Between 2007 and 2019, marijuana use during pregnancy increased from 7.1% to 11.7%, whereas alcohol and opioid use in pregnancy were unchanged. Postpartum alcohol (44.4%), marijuana (13.6%), and concomitant alcohol and marijuana (10.0%) use were common; marijuana use increased from 10.2% to 23.7% from 2007 to 2019, whereas postpartum alcohol use was unchanged. The adjusted mean risk of marijuana use increased by 7% (95% CI, 3%-10%) per year during pregnancy and 11% (95% CI, 7%-16%) per year postpartum. Postpartum concomitant alcohol and marijuana use increased by 10% (95% CI, 5%-15%) per year. Differences in substance use were not associated with recreational legalization, but increased marijuana use was associated with medical marijuana legalization. Conclusions and Relevance: In this cohort study, opioid use among pregnant people living with HIV remained stable, whereas marijuana use during pregnancy and postpartum increased over time and in states with legalized medical marijuana. These patterns of increasing marijuana use among pregnant and postpartum people living with HIV suggest that enhanced clinical attention is warranted, given the potential maternal and child health implications of substance use.

Chronic Stress and Preconception Health Among Latina Women in Metro Atlanta.

BACKGROUND: Underserved subgroups are less likely to have optimal health prior to pregnancy. We describe preconception health indicators (behavior, pregnancy intention, and obesity) among pregnant Latina women with and without chronic stress in metro Atlanta. DESIGN: We surveyed 110 pregnant Latina women enrolled in prenatal care at three clinics in Atlanta. The survey assessed chronic stress, pregnancy intention, preconception behavior changes (taking folic acid or prenatal vitamins, seeking healthcare advice, any reduction in smoking or drinking), and previous trauma. RESULTS: Specific behaviors to improve health prior to pregnancy were uncommon (e.g., taking vitamins (25.5%) or improving nutrition (20.9%)). Just under half of women were experiencing a chronic stressor at the time of conception (49.5%). Chronically stressed women were more likely to be obese (aOR: 3.0 (1.2, 7.4)), less likely to intend their pregnancy (aOR: 0.3 (0.1, 0.7)), and possibly less likely to report any PHB (45.5% vs. 57.4%; aOR: 0.5 (0.2-1.1)). CONCLUSIONS: Chronically stress women were less likely to enter prenatal care with optimal health. However, preconception behaviors were uncommon overall.

Factors that Lengthen Patient Hospitalizations Following Laparoscopic Hysterectomy.

OBJECTIVE: To establish descriptive observations associated with prolonged hospitalization after laparoscopic hysterectomy prior to the implementation of a department-wide Enhanced Recovery After Surgery protocol. METHODS: A retrospective cohort study at three academic affiliated hospitals in the southeastern United States was conducted evaluating length of hospitalization by patient, surgical, and physician factors for 384 patients who underwent total laparoscopic hysterectomy, laparoscopic assisted vaginal hysterectomy, and robotic assisted total laparoscopic hysterectomy for benign conditions by general and subspecialized gynecologists from 2010 to 2015. RESULTS: Among 384 patients, 19.5% experienced prolonged hospitalization, defined as greater than one day. After adjusting for covariates, robotic assisted total laparoscopic hysterectomy (aOR 3.13), dietary restrictions on postoperative day 1 (aOR 4.42), postoperative nausea or vomiting (aOR 2.01), and postoperative complications (aOR 3.58) were associated with prolonged hospitalization. CONCLUSION: Data from this study were collected prior to implementation of department-wide enhanced recovery after surgery protocols and highlights areas for improvement. Implementation of specific aspects of these protocols, including aggressive prevention of postoperative nausea and vomiting and early feeding, are easily made changes which may help to effectively decrease length of stay after laparoscopic hysterectomy. Patient and provider education on enhanced recovery protocols is also key to reducing length of stay.

Gabapentin as an adjunct to paracervical block for perioperative pain management for first-trimester uterine aspiration: a randomized controlled trial.

BACKGROUND: Pain management approaches during uterine aspiration vary, which include local anesthetic, oral analgesics, moderate sedation, deep sedation, or a combination of approaches. For local anesthetic approaches specifically, we continue to have suboptimal pain control. Gabapentin as an adjunct to pain management has proven to be beneficial in gynecologic surgery. We sought to evaluate the impact of gabapentin on perioperative pain during surgical management of first-trimester abortion or early pregnancy loss with uterine aspiration under local anesthesia. OBJECTIVE: We hypothesized that adding gabapentin to local anesthesia will reduce perioperative and postoperative pain associated with uterine aspiration. Secondary outcomes included tolerability of gabapentin and postoperative pain, nausea, vomiting, and anxiety. STUDY DESIGN: We conducted a randomized double-blinded placebo-controlled trial of gabapentin 600 mg given 1 to 2 hours preoperatively among subjects receiving a first-trimester uterine aspiration under paracervical block in an outpatient ambulatory surgery center. There were 111 subjects randomized. The primary outcome was pain at time of uterine aspiration as measured on a 100-mm visual analog scale. Secondary outcomes included pain at other perioperative time points. To assess changes in pain measures, an intention to treat mixed effects model was fit with treatment groups (gabapentin vs control) as a between-subjects factor and time point as a within-subjects factor plus their interaction term. Because of a non-normal distribution of pain scores, the area under the curve was calculated for secondary outcomes with comparison of groups utilizing Mann-Whitney U tests. RESULTS: Among the 111 randomized, most subjects were Black or African American (69.4%), mean age was 26 years (±5.5), and mean gestational age was 61.3 days (standard deviation, 14.10). Mean pain scores at time of uterine aspiration were 66.77 (gabapentin) vs 71.06 (placebo), with a mean difference of -3.38 (P=.51). There were no significant changes in pain score preoperatively or intraoperatively. Subjects who received gabapentin had significantly lower levels of pain at 10 minutes after surgery (mean difference [standard error (SE)]=-13.0 [-5.0]; P=.01) and 30 minutes after surgery (mean difference [SE]=-10.8 [-5.1]; P=.03) compared with subjects who received placebo. Median nausea scores and incidence of emesis pre- and postoperatively did not differ between groups. Similarly, anxiety scores did not differ between groups, before or after the procedure. At 10 and 30 minutes after the procedure, most participants reported no side effects or mild side effects, and this did not differ between groups. CONCLUSION: Preoperative gabapentin did not reduce pain during uterine aspiration. However, it did reduce postoperative pain, which may prove to be a desired attribute of its use, particularly in cases where postoperative pain may be a greater challenge.

Patterns of Screening, Infection, and Treatment of Chlamydia trachomatis and Neisseria gonorrhea in Pregnancy.

OBJECTIVE: To describe factors associated with not being tested for Chlamydia trachomatis and Neisseria gonorrhea infection during pregnancy and for testing positive and to describe patterns of treatment and tests of reinfection. METHODS: We conducted a retrospective cohort study of women who delivered at an urban teaching hospital from July 1, 2016 to June 30, 2018. Women with at least one prenatal care or triage visit were included. The index delivery was included for women with multiple deliveries. We used logistic regression to analyze factors associated with not being tested and for testing positive for these infections in pregnancy. Cox proportional hazards models were used to examine factors associated with time to treatment and tests of reinfection. We reviewed medical records to determine reasons for delays in treatment longer than 1 week. RESULTS: Among 3,265 eligible deliveries, 3,177 (97%) women were tested during pregnancy. Of these, 370 (12%) tested positive (287 chlamydia, 35 gonorrhea, 48 both), and 15% had repeat infections. Prenatal care adequacy and insurance status were risk factors for not being tested. Age, race and ethnicity, alcohol use, and sexually transmitted infection history were associated with testing positive. Time to treatment ranged from 0 to 221 days, with the majority (55%) of patients experiencing delays of more than 1 week. Common reasons for delays included lack of clinician recognition and follow-up of abnormal results (65%) and difficulty contacting the patient (33%). CONCLUSION: Traditional risk factors are associated with increased risk of infection during pregnancy. Prenatal care adequacy and insurance status were associated with the likelihood of being tested. Delays in treatment and tests of reinfection were common. Point-of-care testing and expedited partner therapy should be explored as ways to improve the management of these infections in pregnancy.

Interleukin-36γ Is Elevated in Cervicovaginal Epithelial Cells in Women With Bacterial Vaginosis and In Vitro After Infection With Microbes Associated With Bacterial Vaginosis.

In recent studies, the interleukin (IL)-36 cytokines were shown to be elevated in women with non-Lactobacillus-dominated vaginal microbiomes. In this study, we evaluated IL36G expression in clinical samples from women with and without bacterial vaginosis (BV) and a human 3-dimensional cervical epithelial cell model. IL36G expression was significantly elevated in cervicovaginal epithelial cells isolated from BV-positive women and corresponded with increased neutrophil counts relative to BV-negative women. In addition, specific BV-associated bacterial species as well as a polymicrobial cocktail significantly induced IL36G expression in vitro. These findings suggest that IL-36γ may exhibit an important function in the host response to BV and other sexually transmitted infections.

Miscarriage among women in the United States Women's Interagency HIV Study, 1994-2017.

BACKGROUND: Relatively little is known about the frequency and factors associated with miscarriage among women living with HIV. OBJECTIVE: The objective of the study was to evaluate factors associated with miscarriage among women enrolled in the Women's Interagency HIV Study. STUDY DESIGN: We conducted an analysis of longitudinal data collected from Oct. 1, 1994, to Sept. 30, 2017. Women who attended at least 2 Women's Interagency HIV Study visits and reported pregnancy during follow-up were included. Miscarriage was defined as spontaneous loss of pregnancy before 20 weeks of gestation based on self-report assessed at biannual visits. We modeled the association between demographic, behavioral, and clinical covariates and miscarriage (vs live birth) for women overall and stratified by HIV status using mixed-model logistic regression. RESULTS: Similar proportions of women living with and without HIV experienced miscarriage (37% and 39%, respectively, P = .638). In adjusted analyses, smoking tobacco (adjusted odds ratio, 2.0), alcohol use (adjusted odds ratio, 4.0), and marijuana use (adjusted odds ratio, 2.0) were associated with miscarriage. Among women living with HIV, low HIV viral load (<4 log10 copies/mL) (adjusted odds ratio, 0.5) and protease inhibitor (adjusted odds ratio, 0.4) vs the nonuse of combination antiretroviral therapy use were protective against miscarriage. CONCLUSION: We did not find an increased odds of miscarriage among women living with HIV compared with uninfected women; however, poorly controlled HIV infection was associated with increased miscarriage risk. Higher miscarriage risk among women exposed to tobacco, alcohol, and marijuana highlight potentially modifiable behaviors. Given previous concern about antiretroviral therapy and adverse pregnancy outcomes, the novel protective association between protease inhibitors compared with non-combination antiretroviral therapy and miscarriage in this study is reassuring.

Perceived Barriers to Antepartum HIV Medication Adherence in HIV Infected Pregnant Women.

Introduction: Although rare, perinatal HIV transmission still occurs in the United States and most transmissions are preventable. We aim to identify patient barriers to antiretroviral therapy (ART) adherence during pregnancy and assess patient understanding of perinatal transmission. Methods: This cross-sectional survey recruited HIV positive postpartum women at a large safety net hospital in Atlanta, Georgia, between January 2016 and February 2018. Survey questions included demographic characteristics, HIV history, knowledge of perinatal transmission, and ART adherence. Perinatal and HIV outcomes were assessed using chart abstraction. Results: Of the 70 HIV infected postpartum women delivered at a large safety net hospital in Atlanta, GA, 45 women were eligible and consented to participate. Participating women were aged 18 to 40 years with an average age of 29 years old, 93% of participants were African-American, and 68% had ≥3 pregnancies. The majority of participants (75%) reported daily ART adherence. "Forgetting" was the most frequent reason for missing pills (57%). Thirteen women had a detectable viral load at the time of delivery and nine of those women had a viral load greater than 1000 copies/mL. Approximately 85% of women who correctly stated ART medications decrease perinatal transmission risk reported daily adherence compared with 50% of women without that knowledge (OR 5.6, 95% CI 1.17, 26.7). Almost half of women (40%) either did not know or believed a vaginal delivery, regardless of viral load, would increase their risk of perinatal transmission. Conclusion: Overall, women who were diagnosed with HIV during the current pregnancy, those with planned pregnancies, and those who were on medications prior to pregnancy were more likely to report daily ART adherence. Detectable viral load at delivery is the greatest risk factor for perinatal transmission; therefore strategies to increase ART adherence are needed.

Human Immunodeficiency Virus Serodiscordance and Dual Contraceptive Method Use Among Human Immunodeficiency Virus-infected Men and Women in Lilongwe, Malawi.

BACKGROUND: Some human immunodeficiency virus (HIV) serodiscordant couples are faced with the dual challenge of preventing HIV transmission to the uninfected partner and avoiding unintended pregnancy. Therefore, we hypothesized that serodiscordance is associated with dual method use at last sex. METHODS: We analyzed data from a cross-sectional survey of HIV-infected men and women attending 2 ante-retroviral therapy clinics in Lilongwe, Malawi. We used Fisher exact test and Wilcoxon rank sum to assess for associations between serodiscordance, covariates, and dual method use. Multivariable logistic regression was used to estimate the adjusted odds ratio (aOR) and 95% confidence intervals (CI) of dual method use at last sex, comparing serodiscordant to seroconcordant relationships. Separate analyses were conducted for men and women. RESULTS: We surveyed 253 HIV-infected men, of which 44 (17.4%) were in a known serodiscordant relationship and 63 (24.9%) were using dual methods at last sex. Likewise, among 302 HIV-infected women surveyed, 57 (18.9%) were in a known serodiscordant relationship, and 80 (26.5%) were using dual method at last sex. Serodiscordance was not significantly associated with dual method use at last sex for among HIV-infected men (aOR, 0.62; 95% CI, 0.27-1.44) or women (aOR, 1.21; 95% CI, 0.59-2.47). CONCLUSION: Dual method use was low among all HIV-infected individuals, irrespective of their partner's HIV status. Given these findings, we recommend greater efforts to encourage HIV providers to counsel their patients about the importance of dual method use to prevent both unintended pregnancy and sexually transmitted infections.

Effect of the depot medroxyprogesterone acetate injectable and levonorgestrel implant on HIV genital shedding: a randomized trial.

OBJECTIVES: To assess the effect of the depot medroxyprogesterone acetate injectable (DMPA) and of the levonorgestrel (LNG) implant on genital HIV shedding among women receiving antiretroviral therapy (ART). METHODS: We randomized HIV-infected Malawian women to either DMPA or LNG implant from May 2014 to April 2015. HIV RNA was measured in cervicovaginal lavage (CVL) fluid and TearFlo Strips (TFS), and HIV DNA was measured in cells collected by CVL. We compared the frequency and magnitude of HIV genital shedding before and for 6 months after initiation of contraception and between arms among women receiving ART. We also compared genital HIV RNA levels obtained by sample type (TFS versus CVL). RESULTS: We analyzed data for 68 HIV-infected women receiving ART: 33 randomized to DMPA and 35 randomized to the LNG implant. Overall, HIV RNA was more often detectable and the quantity was higher on TFS compared with CVL. HIV DNA was detected very rarely in CVL cell samples (4 of 360 samples). The frequency of genital shedding and the genital HIV quantity did not increase after contraceptive initiation with either DMPA or LNG implant among women receiving ART. CONCLUSIONS: HIV-infected women receiving ART initiating contraception with either DMPA or LNG implant did not have any increase in genital HIV shedding during the first 6 months of contraceptive use. These findings are consistent with growing evidence that progestin contraception is not associated with increased HIV transmission risk from such women to their male partners. Consistent with other studies, genital HIV RNA detection was higher in TFS than in CVL fluid. IMPLICATIONS: In this randomized trial, neither DMPA nor the LNG implant, two of the most commonly used hormonal contraceptives among African women with HIV, was associated with increased genital HIV shedding in HIV-infected women receiving ART. These findings are reassuring and add to the currently limited information available for the highly effective contraceptive, LNG implant.

Access to Fertility Treatment for Mixed-Status Couples With Human Immunodeficiency Virus.

In an effort to place the recent Centers for Disease Control and Prevention Morbidity and Mortality Weekly Report publications regarding conception options for mixed-status couples with human immunodeficiency virus (HIV) in perspective, we review the historical evolution of conception options for mixed-status couples with HIV with particular focus on the potential need for fertility treatment and the feasibility of accessing such treatment.

Interest in multipurpose prevention technologies to prevent HIV/STIs and unintended pregnancy among young women in the United States.

OBJECTIVE: High rates of sexually transmitted infections (STIs) and unintended pregnancy suggest a role for multipurpose prevention technologies (MPTs) designed to combine contraception and infection prophylaxis into one unified method. This study aims to determine factors associated with interest in MPTs among US women. STUDY DESIGN: We administered a national cross-sectional survey via MTurk. Eligibility criteria included female gender, age 18-29 years, residence in the USA, and sexual activity with a male partner in the past three months. In total, 835 surveys were suitable for analysis. Bivariable and multivariable logistic regressions were performed to determine factors associated with interest in MPTs. RESULTS: Eighty-three percent of women were interested in MPTs. Factors associated with interest included oral sex in the past three months (aOR 1.87, 95% CI 1.07, 3.53), recent use of oral contraceptive pills (OCPs; aOR 1.78, 95% CI 1.08, 2.93), HIV test within one year (aOR 2.10, 95% CI 1.29, 3.40), and increased STI worry score (aOR 1.98, 95% CI 1.36, 2.86). No use of contraception in the past three months was associated with decreased interest in MPTs (aOR 0.31, 95% CI 0.17, 0.58). HIV risk factors including race were not associated with MPT interest. CONCLUSION: Our data show that young, sexually active, US women are interested in MPTs. Women who used contraception, specifically OCPs, or evidenced concern for infection were most likely to be interested in such a product. Women reporting unsafe sexual habits were less likely to be interested, highlighting the importance of HIV/STI prevention education. IMPLICATIONS: Women in the USA are interested in multipurpose prevention technologies, particularly those women who currently use contraception or are concerned about their risk of infection. Our results emphasize the importance of moving forward with MPT development as well as continued HIV/STI prevention education.

Risk of heterosexual HIV transmission attributable to sexually transmitted infections and non-specific genital inflammation in Zambian discordant couples, 1994-2012.

Background: Studies have demonstrated the role of ulcerative and non-ulcerative sexually transmitted infections (STI) in HIV transmission/acquisition risk; less is understood about the role of non-specific inflammatory genital abnormalities. Methods: HIV-discordant heterosexual Zambian couples were enrolled into longitudinal follow-up (1994-2012). Multivariable models estimated the effect of genital ulcers and inflammation in both partners on time-to-HIV transmission within the couple. Population-attributable fractions (PAFs) were calculated. Results: A total of 207 linked infections in women occurred over 2756 couple-years (7.5/100 CY) and 171 in men over 3216 CY (5.3/100 CY). Incident HIV among women was associated with a woman's non-STI genital inflammation (adjusted hazard ratio (aHR) = 1.55; PAF = 8%), bilateral inguinal adenopathy (BIA; aHR = 2.33; PAF = 8%), genital ulceration (aHR = 2.08; PAF = 7%) and the man's STI genital inflammation (aHR = 3.33; PAF = 5%), BIA (aHR = 3.35; PAF = 33%) and genital ulceration (aHR = 1.49; PAF = 9%). Infection among men was associated with a man's BIA (aHR = 4.11; PAF = 22%) and genital ulceration (aHR = 3.44; PAF = 15%) as well as with the woman's non-STI genital inflammation (aHR = 1.92; PAF = 13%) and BIA (aHR = 2.76; PAF = 14%). In HIV-M+F- couples, the man being uncircumcised. with foreskin smegma. was associated with the woman's seroconversion (aHR = 3.16) relative to being circumcised. In F+M- couples, uncircumcised men with BIA had an increased hazard of seroconversion (aHR = 13.03 with smegma and 4.95 without) relative to being circumcised. Self-reporting of symptoms was low for ulcerative and non-ulcerative STIs. Conclusions: Our findings confirm the role of STIs and highlight the contribution of non-specific genital inflammation to both male-to-female and female-to-male HIV transmission/acquisition risk. Studies are needed to characterize pathogenesis of non-specific inflammation including inguinal adenopathy. A better understanding of genital practices could inform interventions.

Severe Neurologic Disorders in 2 Fetuses with Zika Virus Infection, Colombia.

We report the results of pathologic examinations of 2 fetuses from women in Colombia with Zika virus infection during pregnancy that revealed severe central nervous system defects and potential associated abnormalities of the eye, spleen, and placenta. Amniotic fluid and tissues from multiple fetal organs tested positive for Zika virus.

Progesterone Levels Associate with a Novel Population of CCR5+CD38+ CD4 T Cells Resident in the Genital Mucosa with Lymphoid Trafficking Potential.

The female genital tract (FGT) provides a means of entry to pathogens, including HIV, yet immune cell populations at this barrier between host and environment are not well defined. We initiated a study of healthy women to characterize resident T cell populations in the lower FGT from lavage and patient-matched peripheral blood to investigate potential mechanisms of HIV sexual transmission. Surprisingly, we observed FGT CD4 T cell populations were primarily CCR7(hi), consistent with a central memory or recirculating memory T cell phenotype. In addition, roughly half of these CCR7(hi) CD4 T cells expressed CD69, consistent with resident memory T cells, whereas the remaining CCR7(hi) CD4 T cells lacked CD69 expression, consistent with recirculating memory CD4 T cells that traffic between peripheral tissues and lymphoid sites. HIV susceptibility markers CCR5 and CD38 were increased on FGT CCR7(hi) CD4 T cells compared with blood, yet migration to the lymphoid homing chemokines CCL19 and CCL21 was maintained. Infection with GFP-HIV showed that FGT CCR7(hi) memory CD4 T cells are susceptible HIV targets, and productive infection of CCR7(hi) memory T cells did not alter chemotaxis to CCL19 and CCL21. Variations of resident CCR7(hi) FGT CD4 T cell populations were detected during the luteal phase of the menstrual cycle, and longitudinal analysis showed the frequency of this population positively correlated to progesterone levels. These data provide evidence women may acquire HIV through local infection of migratory CCR7(hi) CD4 T cells, and progesterone levels predict opportunities for HIV to access these novel target cells.

Contraceptive methods and risk of HIV acquisition or female-to-male transmission.

Effective family planning with modern contraception is an important intervention to prevent unintended pregnancies which also provides personal, familial, and societal benefits. Contraception is also the most cost-effective strategy to reduce the burden of mother-to-child HIV transmission for women living with HIV who wish to prevent pregnancy. There are concerns, however, that certain contraceptive methods, in particular the injectable contraceptive depot medroxyprogesterone acetate (DMPA), may increase a woman's risk of acquiring HIV or transmitting it to uninfected males. These concerns, if confirmed, could potentially have large public health implications. This paper briefly reviews the literature on use of contraception among women living with HIV or at high risk of HIV infection. The Centers for Disease Control and Prevention (CDC) and the World Health Organization (WHO) recommendations place no restrictions on the use of hormonal contraceptive methods by women with or at high risk of HIV infection, although a clarification recommends that, given uncertainty in the current literature, women at high risk of HIV who choose progestogen-only injectable contraceptives should be informed that it may or may not increase their risk of HIV acquisition and should also be informed about and have access to HIV preventive measures, including male or female condoms.