C. Christina Mehta

Trends of and factors associated with live-birth and abortion rates among HIV-positive and HIV-negative women

BACKGROUND: Little is known about fertility choices and pregnancy outcome rates among HIV‐infected women in the current combination antiretroviral treatment era. OBJECTIVE: We sought to describe trends and factors associated with live‐birth and abortion rates among HIV‐positive and high‐risk HIV‐negative women enrolled in the Womens Interagency HIV Study in the United States. STUDY DESIGN: We analyzed longitudinal data collected from Oct. 1, 1994, through Sept. 30, 2012, through the Womens Interagency HIV Study. Age‐adjusted rates per 100 person‐years live births and induced abortions were calculated by HIV serostatus over 4 time periods. Poisson mixed effects models containing variables associated with live births and abortions in bivariable analyses (P < .05) generated adjusted incidence rate ratios and 95% confidence intervals. RESULTS: There were 1356 pregnancies among 2414 women. Among HIV‐positive women, age‐adjusted rates of live birth increased from 1994 through 1997 to 2006 through 2012 (2.85‐7.27/100 person‐years, P trend < .0001). Age‐adjusted rates of abortion in HIV‐positive women remained stable over these time periods (4.03‐4.29/100 person‐years, P trend = .09). Significantly lower live‐birth rates occurred among HIV‐positive compared to HIV‐negative women in 1994 through 1997 and 1997 through 2001, however rates were similar during 2002 through 2005 and 2006 through 2012. Higher CD4+ T cells/mm3 (≥350 adjusted incidence rate ratio, 1.39 [95% CI 1.03‐1.89] vs <350) were significantly associated with increased live‐birth rates, while combination antiretroviral treatment use (adjusted incidence rate ratio, 1.35 [95% CI 0.99‐1.83]) was marginally associated with increased live‐birth rates. Younger age, having a prior abortion, condom use, and increased parity were associated with increased abortion rates among both HIV‐positive and HIV‐negative women. CD4+ T‐cell count, combination antiretroviral treatment use, and viral load were not associated with abortion rates. CONCLUSION: Unlike earlier periods (pre‐2001) when live‐birth rates were lower among HIV‐positive women, rates are now similar to HIV‐negative women, potentially due to improved health status and combination antiretroviral treatment. Abortion rates remain unchanged, illuminating a need to improve contraceptive services.

Association of Overlapping Surgery With Patient Outcomes in a Large Series of Neurosurgical Cases

Importance Overlapping surgery (OS) is common. However, there is a dearth of evidence to support or refute the safety of this practice. Objective To determine whether OS is associated with worsened morbidity and mortality in a large series of neurosurgical cases. Design, Setting, and Participants A retrospective cohort study was completed for patients who underwent neurosurgical procedures at Emory University Hospital, a large academic referral hospital, between January 1, 2014, and December 31, 2015. Patients were operated on for pathologies across the spectrum of neurosurgical disorders. Propensity score weighting and logistic regression models were executed to compare outcomes for patients who received nonoverlapping surgery and OS. Investigators were blinded to study cohorts during data collection and analysis. Main Outcomes and Measures The primary outcome measures were 90-day postoperative mortality, morbidity, and functional status. Results In this cohort of 2275 patients who underwent neurosurgery, 1259 (55.3%) were female, and the mean (SD) age was 52.1 (16.4) years. A total of 972 surgeries (42.7%) were nonoverlapping while 1303 (57.3%) were overlapping. The distribution of American Society of Anesthesiologists score was similar between nonoverlapping surgery and OS cohorts. Median surgical times were significantly longer for patients in the OS cohort vs the nonoverlapping surgery cohort (in-room time, 219 vs 188 minutes; skin-to-skin time, 141 vs 113 minutes; both P < .001). Overlapping surgery was more frequently elective (93% vs 87%; P < .001). Regression analysis failed to demonstrate an association between OS and complications, such as mortality, morbidity, or worsened functional status. Measures of baseline severity of illness, such as admission to the intensive care unit and increased length of stay, were associated with mortality (intensive care unit: odds ratio [OR], 25.5; 95% CI, 6.22-104.67; length of stay: OR, 1.03; 95% CI, 1.00-1.05), morbidity (intensive care unit: OR, 1.85; 95% CI, 1.43-2.40; length of stay: OR, 1.06; 95% CI, 1.04-1.08), and unfavorable functional status (length of stay: OR, 1.03; 95% CI, 1.02-1.05). Conclusions and Relevance These data suggest that OS can be safely performed if appropriate precautions and patient selection are followed. Data such as these will help determine health care policy to maximize patient safety.

The Female Genital Tract Microbiome Is Associated With Vaginal Antiretroviral Drug Concentrations in Human Immunodeficiency Virus–Infected Women on Antiretroviral Therapy

Background The female genital tract (FGT) microbiome may affect vaginal pH and other factors that influence drug movement into the vagina. We examined the relationship between the microbiome and antiretroviral concentrations in the FGT. Methods Over one menstrual cycle, 20 human immunodeficiency virus (HIV)-infected women virologically suppressed on tenofovir (TFV) disoproxil fumarate/emtricitabine and ritonavir-boosted atazanavir (ATV) underwent serial paired cervicovaginal and plasma sampling for antiretroviral concentrations using high-performance liquid chromatography-tandem mass spectrometry. Analysis of 16S ribosomal RNA gene sequencing of cervicovaginal lavage clustered each participant visit into a unique microbiome community type (mCT). Results Participants were predominantly African American (95%), with a median age of 38 years. Cervicovaginal lavage sequencing (n = 109) resulted in a low-diversity mCT dominated by Lactobacillus (n = 40), and intermediate-diversity (n = 28) and high-diversity (n = 41) mCTs with abundance of anaerobic taxa. In multivariable models, geometric mean FGT:plasma ratios varied significantly by mCT for all 3 drugs. For both ATV and TFV, FGT:plasma was significantly lower in participant visits with high- and low-diversity mCT groups (all P < .02). For emtricitabine, FGT:plasma was significantly lower in participant visits with low- vs intermediate-diversity mCT groups (P = .002). Conclusions Certain FGT mCTs are associated with decreased FGT antiretroviral concentrations. These findings are relevant for optimizing antiretrovirals used for biomedical HIV prevention in women.

Characteristics of HIV target CD4 T cells collected using different sampling methods from the genital tract of HIV seronegative women

Background Understanding the immune profile of CD4 T cells, the primary targets for HIV, in the female genital tract (FGT) is critical for evaluating and developing effective biomedical HIV prevention strategies in women. However, longitudinal investigation of HIV susceptibility markers expressed by FGT CD4 T cells has been hindered by low cellular yield and risk of sampling-associated trauma. We investigated three minimally invasive FGT sampling methods to characterize and compare CD4 T cell yield and phenotype with the goal of establishing feasible sampling strategies for immune profiling of mucosal CD4 T cells. Methods and results FGT samples were collected bimonthly from 12 healthy HIV negative women of reproductive age in the following order: 1) Cervicovaginal lavage (CVL), 2) two sequential endocervical flocked swabs (FS), and 3) two sequential endocervical cytobrushes (CB1, CB2). Cells were isolated and phentoyped via flow cytometry. CD4 T cell recovery was highest from each individual CB compared to either CVL or FS (p < 0.0001). The majority of CD4 T cells within the FGT, regardless of sampling method, expressed CCR5 relative to peripheral blood (p < 0.01). Within the CB, CCR5+ CD4 T cells expressed significantly higher levels of α4β7, CD69, and low levels of CD27 relative to CCR5- CD4 T cells (all p < 0.001). We also identified CD4 Treg lineage cells expressing CCR5 among CB samples. Conclusions Using three different mucosal sampling methods collected longitudinally we demonstrate that CD4 T cells within the FGT express CCR5 and α4β7 and are highly activated, attributes which could act in concert to facilitate HIV acquisition. FS and CB sampling methods can allow for investigation of strategies to reduce HIV target cells in the FGT and could inform the design and interpretation microbicide and vaccine studies in women.

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.

The association of C-reactive protein with subclinical cardiovascular disease in HIV-infected and HIV-uninfected women

Objective: HIV is a cardiovascular disease (CVD) risk factor. However, CVD risk is often underestimated in HIV-infected women. C-reactive protein (CRP) may improve CVD prediction in this population. We examined the association of baseline plasma CRP with subclinical CVD in women with and without HIV. Design: Retrospective cohort study. Methods: A total of 572 HIV-infected and 211 HIV-uninfected women enrolled in the Womens Interagency HIV Study underwent serial high-resolution B-mode carotid artery ultrasonography between 2004 and 2013 to assess carotid intima–media thickness (CIMT) and focal carotid artery plaques. We used multivariable linear and logistic regression models to assess the association of baseline high (≥3 mg/l) high-sensitivity (hs) CRP with baseline CIMT and focal plaques, and used multivariable linear and Poisson regression models for the associations of high hsCRP with CIMT change and focal plaque progression. We stratified our analyses by HIV status. Results: Median (interquartile range) hsCRP was 2.2 mg/l (0.8–5.3) in HIV-infected, and 3.2 mg/l (0.9–7.7) in HIV-uninfected, women (P = 0.005). There was no statistically significant association of hsCRP with baseline CIMT [adjusted mean difference −3.5 &mgr;m (95% confidence interval:−19.0 to 12.1)] or focal plaques [adjusted odds ratio: 1.31 (0.67–2.67)], and no statistically significant association of hsCRP with CIMT change [adjusted mean difference 11.4 &mgr;m (−2.3 to 25.1)]. However, hsCRP at least 3 mg/l was positively associated with focal plaque progression in HIV-uninfected [adjusted rate ratio: 5.97 (1.46–24.43)], but not in HIV-infected [adjusted rate ratio: 0.81 (0.47–1.42)] women (P = 0.042 for interaction). Conclusion: In our cohort of women with similar CVD risk factors, higher baseline hsCRP is positively associated with carotid plaque progression in HIV-uninfected, but not HIV-infected, women, suggesting that subclinical CVD pathogenesis may be different HIV-infected women.

Contact networks in the emergency department: Effects of time, environment, patient characteristics, and staff role

Abstract Emergency departments play a critical role in the public health system, particularly in times of pandemic. Infectious patients presenting to emergency departments bring a risk of cross-infection to other patients and staff through close proximity interactions or contacts. To understand factors associated with cross-infection risk, we measured close proximity interactions of emergency department staff and patients by radiofrequency identification in a working emergency department. The number of contacts (degree) is not related to patient demographic characteristics. However, the amount of time in close proximity (weighted degree) of patients with ED personnel did differ, with black patients having approximately 15min more contact with staff than non-white patients. Patients arriving by EMS had fewer contacts with other patients than patients arriving by other means. There are differences in the number of contacts based on staff role and arrival mode. When crowding is low, providers have the most contact time with patients, while administrative staff have the least. However, when crowding is high, this differential is reversed. The effect of arrival mode is modified by the extent of crowding. When crowding is low, patients arriving by EMS had longer contact with administrative staff, compared to patients arriving by other means. However, when crowding is high, patients arriving by EMS had less contact with administrative staff compared to patients arriving by other means. Our findings should help designers of emergency care focus on higher risk situations for transmission of dangerous pathogens in an emergency department. For instance, the effects of arrival and crowding should be considered as targets for engineering or architectural interventions that could artificially increase social distances.

Neutrophil extracellular trap (NET) levels in human plasma are associated with active TB

Neutrophils are increasingly associated with tuberculosis (TB) disease. Neutrophil extracellular traps (NETs), which are released by neutrophils as a host antimicrobial defense mechanism, are also associated with tissue damage. However, a link between NET levels and TB disease has not been studied. Here we investigate plasma NETs levels in patients with active pulmonary tuberculosis using an ELISA assay that is suitable for high-throughput processing. We show that plasma NETs levels at baseline correlated with disease severity and decreased with antibiotic therapy. Our study demonstrates the biologic plausibility of measuring NETs in plasma samples from patients with TB.

Implementation of a Rapid Entry Program Decreases Time to Viral Suppression Among Vulnerable Persons Living With HIV in the Southern United States

Abstract Background Rapid entry programs (REPs) improve time to antiretroviral therapy (ART) initiation (TAI) and time to viral suppression (TVS). We assessed the feasibility and effectiveness of a REP in a large HIV clinic in Atlanta, Georgia, serving a predominately un- or underinsured population. Methods The Rapid Entry and ART in Clinic for HIV (REACH) program was implemented on May 16, 2016. We performed a retrospective cohort study with the main independent variable being period of enrollment: January 1, 2016, through May 15, 2016 (pre-REACH); May 16, 2016, through July 31, 2016 (post-REACH). Included individuals were HIV-infected and new to the clinic with detectable HIV-1 RNA. Six-month follow-up data were collected for each participant. Survival analyses were conducted for TVS. Logistic and linear regression analyses were used to evaluate secondary outcomes: attendance at first clinic visit, viral suppression, TAI, and time to first attended provider visit. Results There were 117 pre-REACH and 90 post-REACH individuals. Median age (interquartile range [IQR]) was 35 (25–45) years, 80% were male, 91% black, 60% men who have sex with men, 57% uninsured, and 44% active substance users. TVS decreased from 77 (62–96) to 57 (41–70) days (P < .0022). Time to first attended provider visit decreased from 17 to 5 days, and TAI from 21 to 7 days (P < .0001), each remaining significant in adjusted models. Conclusions This is the largest rapid entry cohort described in the United States and suggests that rapid entry is feasible and could have a positive impact on HIV transmission at the population level.

Room for Improvement: The HIV-Diabetes Care Continuum Over 15 Years in the Women's Interagency HIV Study

Abstract Background Gains in life expectancy through optimal control of HIV infection with antiretroviral therapy (ART) may be threatened if other comorbidities, such as diabetes, are not optimally managed. Methods We analyzed cross-sectional data of the Women’s Interagency HIV Study (WIHS) from 2001, 2006, and 2015. We estimated the proportions of HIV-positive and HIV-negative women with diabetes who were engaged in care and achieved treatment goals (hemoglobin A1c [A1c] <7.0%, blood pressure [BP] <140/90 mmHg, low-density lipoprotein [LDL] cholesterol <100 mg/dL, not smoking) and viral suppression. Repeated-measures models were used to estimate the adjusted prevalence of achieving each diabetes treatment goal at each time point, by HIV status. Results We included 486 HIV-positive and 258 HIV-negative women with diabetes. In 2001, 91.8% visited a health care provider, 60.7% achieved the A1c target, 70.5% achieved the BP target, 38.5% achieved the LDL cholesterol target, 49.2% were nonsmokers, 23.3% achieved combined ABC targets (A1c, BP, and cholesterol), and 10.9% met combined ABC targets and did not smoke. There were no differences by HIV status, and patterns were similar in 2006 and 2015. Among HIV-positive women, viral suppression increased from 41% in 2001 to 87% in 2015 compared with 8% and 13% achieving the ABC goals and not smoking. Viral suppression was not associated with achievement of diabetes care goals. Conclusions Successful management of HIV is outpacing that of diabetes. Future studies are needed to identify factors associated with gaps in the HIV–diabetes care continuum and design interventions to better integrate effective diabetes management into HIV care.