Clinically relevant antibiotic resistance genes are linked to a limited set of taxa within gut microbiome worldwide.

The acquisition of antimicrobial resistance (AR) genes has rendered important pathogens nearly or fully unresponsive to antibiotics. It has been suggested that pathogens acquire AR traits from the gut microbiota, which collectively serve as a global reservoir for AR genes conferring resistance to all classes of antibiotics. However, only a subset of AR genes confers resistance to clinically relevant antibiotics, and, although these AR gene profiles are well-characterized for common pathogens, less is known about their taxonomic associations and transfer potential within diverse members of the gut microbiota. We examined a collection of 14,850 human metagenomes and 1666 environmental metagenomes from 33 countries, in addition to nearly 600,000 isolate genomes, to gain insight into the global prevalence and taxonomic range of clinically relevant AR genes. We find that several of the most concerning AR genes, such as those encoding the cephalosporinase CTX-M and carbapenemases KPC, IMP, NDM, and VIM, remain taxonomically restricted to Proteobacteria. Even cfiA, the most common carbapenemase gene within the human gut microbiome, remains tightly restricted to Bacteroides, despite being found on a mobilizable plasmid. We confirmed these findings in gut microbiome samples from India, Honduras, Pakistan, and Vietnam, using a high-sensitivity single-cell fusion PCR approach. Focusing on a set of genes encoding carbapenemases and cephalosporinases, thus far restricted to Bacteroides species, we find that few mutations are required for efficacy in a different phylum, raising the question of why these genes have not spread more widely. Overall, these data suggest that globally prevalent, clinically relevant AR genes have not yet established themselves across diverse commensal gut microbiota.

A community health worker-led program to improve access to gestational diabetes screening in urban slums of Pune, India: Results from a mixed methods study.

The World Health Organization recommends all pregnant women receive screening for gestational diabetes (GDM) with a fasting oral glucose tolerance test (OGTT). However, very few women receive recommended screening in resource-limited countries like India. We implemented a community health worker (CHW)-delivered program to evaluate if home-based, CHW-delivered OGTT would increase GDM screening in a low-resource setting. We conducted a mixed methods study in two urban slum communities in Pune, India. CHWs were trained to deliver home-based, point-of-care fasting OGTT to women in their third trimester of pregnancy. The primary outcome was uptake of CHW-delivered OGTT. Secondary outcomes included GDM prevalence and linkage to GDM care. Individual interviews were conducted with purposively sampled pregnant women, CHWs, and local clinicians to assess barriers and facilitators of this approach. From October 2021-June 2022, 248 eligible pregnant women were identified. Of these, 223 (90%) accepted CHW-delivered OGTT and 31 (14%) were diagnosed with GDM. Thirty (97%) women diagnosed with GDM subsequently sought GDM care; only 10 (33%) received lifestyle counseling or pharmacologic therapy. Qualitative interviews indicated that CHW-delivered testing was considered highly acceptable as home-based testing saved time and was more convenient than clinic-based testing. Inconsistent clinical management of GDM was attributed to providers' lack of time to deliver counseling, and perceptions that low-income populations are not at risk for GDM. Convenience and trust in a CHW-delivered GDM screening program resulted in high access to gold-standard OGTT screening and identification of a high GDM prevalence among pregnant women in two urban slum communities. Appropriate linkage to care was limited by clinician time constraints and misperceptions of GDM risk. CHW-delivered GDM screening and counseling may improve health education and access to preventive healthcare, offloading busy public clinics in high-need, low-resource settings.

Association of Pregnancy and HIV Status With Molecular-Bacterial Vaginosis in Indian Women.

BACKGROUND: Bacterial vaginosis (BV) is a highly prevalent disorder of the cervicovaginal microbiota. Molecular-BV may put women at increased risk for adverse reproductive and obstetric outcomes. We investigated the association of HIV and pregnancy on the vaginal microbiota and associations with molecular-BV in women of reproductive age from Pune, India. SETTING: We studied vaginal samples from N = 170 women, including N = 44 nonpregnant HIV seronegative, N = 56 pregnant seronegative, N = 47 nonpregnant women with HIV (WWH), and N = 23 pregnant WWH, and collected data on clinical, behavioral, and demographic factors. METHODS: We used 16S rRNA gene amplicon sequencing to characterize the composition of the vaginal microbiota. We classified the vaginal microbiota of these women into community state types based on bacterial composition and relative abundance and further categorized them into molecular-BV versus Lactobacillus -dominated states. To determine associations between pregnancy and HIV status with outcome of molecular-BV, logistic regression models were used. RESULTS: There was a high prevalence of molecular-BV (30%) in this cohort. We found that pregnancy was associated with decreased odds of molecular-BV (adjusted OR = 0.35, 95% CI: 0.14 to 0.87), while HIV was associated with increased odds of molecular-BV (adjusted OR = 2.76, 95% CI: 1.33 to 5.73), even when controlling for multiple relevant factors such as age, number of sexual partners, condom use, and douching. CONCLUSION: Larger and longitudinal studies are needed to further characterize molecular-BV and the vaginal microbiota in pregnant women and WWH and relate these factors to infectious, reproductive, and obstetric outcomes. In the long term, these studies may lead to novel microbiota-based therapeutics to improve women's reproductive and obstetric health.

"Mobilizing our leaders": A multi-country qualitative study to increase the representation of women in global health leadership.

INTRODUCTION: Women play an essential role in health care delivery, and it is vital that they have equal representation in health leadership for equity, innovation, and the strengthening of health systems globally. Yet women remain vastly underrepresented in global health leadership positions, providing a clear example of the deeply rooted power imbalances that are central to the calls to decolonize global health. We conducted a multi-country study in Haiti, Tanzania, India, and the USA to examine gender-based challenges to career advancement for women in the global health workforce. Quantitative data on the type and prevalence of gender-based challenges has been previously reported. In this study, we analyze qualitative data collected through focus group discussions and in-depth interviews to understand women's experiences of gender-based obstacles to career advancement, their perceptions of underlying drivers, and perspectives on effective solutions. Guided by an adaptation of the Social Action Theory, we conducted focus group discussions and in-depth interviews with women at 4 major academic centers for clinical care and research in Haiti, India, Tanzania, and the United States. In total, 85 women participated in focus groups and 15 also participated in in-depth interviews. Discussions and interviews were conducted in the local language, by an experienced local facilitator unaffiliated with the participating institution, between 2017 and 2018. Discussions were recorded, transcribed, and translated. Data were analyzed by interpretive phenomenological methods for emergent themes. Three transcendent themes on gender-based challenges were identified: 1) cultural power imbalance, referring to the prevailing norms and engrained assumptions that women are less capable than men and that women's primary responsibility should be to their families; 2) institutional power imbalance, referring to the systematic gender bias upheld by existing leadership and power structures, and ranging from exclusion from career development opportunities to sexual harassment and assault; and 3) restricted agency, referring to women's limited ability to change their circumstances because of unequal cultural and institutional structures. Participants also described local, actionable solutions to address these barriers. These included: 1) formal reporting systems for sexual harassment and assault; 2) peer support and mentorship; and 3) accessible leadership training and mandatory gender equity training. Participants proposed feasible strategies to address gender-based challenges that could improve women's retention in health careers and foster their rise to leadership. Increasing the representation of women in global health leadership positions responds directly to efforts to decolonize global health and is integral to strengthening health systems and improving health outcomes for women and children worldwide.

Tuberculosis Infection in Pregnant People: Current Practices and Research Priorities.

Women are significantly more likely to develop tuberculosis (TB) disease within the first 90 days after pregnancy than any other time in their lives. Whether pregnancy increases risk of progression from TB infection (TBI) to TB disease is unknown and is an active area of investigation. In this review, we discuss the epidemiology of TB and TBI in pregnancy, TBI diagnostics, and prevalence in pregnancy. We also review TBI treatment and highlight research priorities, such as short-course TB prevention regimens, drug-resistant TB prevention, and additional considerations for safety, tolerability, and pharmacokinetics that are unique to pregnant and postpartum people.

Evidence for Implementation: Management of TB in HIV and Pregnancy.

PURPOSE OF REVIEW: Pregnant people living with HIV (PLWH) are at especially high risk for progression from latent tuberculosis infection (LTBI) to active tuberculosis (TB) disease. Among pregnant PLWH, concurrent TB increases the risk of complications such as preeclampsia, intrauterine fetal-growth restriction, low birth weight, preterm-delivery, perinatal transmission of HIV, and admission to the neonatal intensive care unit. The grave impact of superimposed TB disease on maternal morbidity and mortality among PLWH necessitates clear guidelines for concomitant therapy and an understanding of the pharmacokinetics (PK) and potential drug-drug interactions (DDIs) between antitubercular (anti-TB) agents and antiretroviral therapy (ART) in pregnancy. RECENT FINDINGS: This review discusses the currently available evidence on the use of anti-TB agents in pregnant PLWH on ART. Pharmacokinetic and safety studies of anti-TB agents during pregnancy and postpartum are limited, and available data on second-line and newer anti-TB agents used in pregnancy suggest that several research gaps exist. DDIs between ART and anti-TB agents can decrease plasma concentration of ART, with the potential for perinatal transmission of HIV. Current recommendations for the treatment of LTBI, drug-susceptible TB, and multidrug-resistant TB (MDR-TB) are derived from observational studies and case reports in pregnant PLWH. While the use of isoniazid, rifamycins, and ethambutol in pregnancy and their DDIs with various ARTs are well-characterized, there is limited data on the use of pyrazinamide and several new and second-line antitubercular drugs in pregnant PLWH. Further research into treatment outcomes, PK, and safety data for anti-TB agent use during pregnancy and postpartum is urgently needed.

Inflammatory profile associated with insulin resistance in non-overweight versus overweight people living with HIV in Pune, Western India.

BACKGROUND: People living with HIV have greater diabetes (T2DM) than the general population despite lower prevalence of overweight/obesity. Both insulin resistance (IR), a T2DM precursor, and HIV are independently associated with chronic inflammation. Inflammation may be a pathophysiological link explaining IR in people living with HIV who are not overweight but is not well understood. AIMS: To study the association between inflammation and IR in non-overweight and overweight people living with HIV. METHODS: In a cohort of adult people living with HIV with undetectable viral load in Pune, India, we measured fasting insulin, glucose, and 9 inflammatory markers. IR was defined as HOMA-IR ≥2, and non-overweight as BMI ≤23 kg/m2. We used modified Poisson regression to evaluate the association between inflammatory markers and IR in overweight and non-overweight. RESULTS: Of 288 participants, 66% (n = 189) were non-overweight. Among non-overweight, prevalence of IR was 34% (n = 65). Each doubling of MCP-1 and leptin was associated with IR on univariate analysis (prevalence ratio (PR) 1.29, 95%CI 1.07-1.53, p < 0.01; PR 1.13 95%CI 1.01-1.26, p = 0.03). Leptin remained associated with IR after adjustment for age, MCP-1, gender, cholesterol, and waist circumference (adjusted PR 1.20 95%CI 1.06-1.36, p < 0.01). Among overweight, prevalence of IR was 69% and no markers were associated with IR. CONCLUSIONS: One in 3 non-overweight people living with HIV in India with controlled viremia have IR. Leptin was associated with IR among non-overweight people living with HIV and may provide insight into the pathophysiology of metabolic disease in this population.

Transcriptional Analysis for Tuberculosis in Pregnant Women From the PRegnancy Associated Changes In Tuberculosis Immunology (PRACHITi) Study.

A new tuberculosis (TB) diagnostic cartridge assay, which detects a 3-gene TB signature in whole blood, was not diagnostic in women with maternal TB disease in India (area under the curve [AUC] = 0.72). In a cohort of pregnant women, we identified a novel gene set for TB diagnosis (AUC = 0.97) and one for TB progression (AUC = 0.96).

Sex differences in cytokine profiles during suppressive antiretroviral therapy.

OBJECTIVE: Despite lower plasma HIV RNA levels, women progress faster to AIDS than men. The reasons for these differences are not clear but might be a consequence of an elevated inflammatory response in women. METHODS: We investigated sex differences in cytokine profiles by measuring the concentrations of 36 cytokines/chemokines by Luminex in blood of women and men (sex at birth) with chronic HIV infection under suppressive therapy. We initially performed a principal component analysis to see if participants clustered by sex, and then fit a partial least squares discriminant analysis (PLS-DA) model where we used cytokines to predict sex at birth. The significance of the difference in nine cytokines with VIP greater than 1 was tested using Wilcoxon test-rank. Further, potential confounding factors were tested by multivariate linear regression models. RESULTS: Overall, we predicted sex at birth in the PLS-DA model with an error rate of approximately 13%. We identified five cytokines, which were significantly higher in women compared with men, namely the pro-inflammatory chemokines CXCL1 (Gro-α), CCL5 (RANTES), CCL3 (MIP-1α), CCL4 (MIP-1ß), as well as the T-cell homeostatic factor IL-7. The effect of sex remained significant after adjusting for CD4 + , age, ethnicity, and race for all cytokines, except for CCL3 and race. CONCLUSION: The observed sex-based differences in cytokines might contribute to higher immune activation in women compared with men despite suppressive therapy. Increased levels of IL-7 in women suggest that homeostatic proliferation may have a differential contribution to HIV reservoir maintenance in female and male individuals. Our study emphasizes the importance of sex-specific studies of viral pathogenesis.

Validation and application of a quantitative liquid chromatography tandem mass spectrometry assay for the analysis of rifapentine and 25-O-desacetyl rifapentine in human milk.

A robust analytical method based on liquid chromatography coupled to tandem mass spectrometry was developed and validated to quantify rifapentine and 25-O-desacetyl rifapentine in human breast milk to aid in determining the breastfed infant risk to the excreted drug in human milk. Samples were extracted by a combination of protein precipitation and solid phase extraction using rifampicin-d3 as an internal standard. An Agilent® Poroshell 120 EC-C18 (4.6 mm × 50 mm, 2.7 µm) column was used for chromatographic separation employing an isocratic mobile phase consisting of acetonitrile: methanol: 0.1% formic acid (55/5/40, v/v/v) at a flow rate of 450 µL/min, and with a total run time of four minutes. Mass detection was on an AB Sciex API 4000 mass spectrometer using electrospray ionization in the positive mode and based on multiple reaction monitoring data acquisition. Rifapentine was accurately quantified across a concentration range of 2.00-2000 ng/mL and 25-O-desacetyl rifapentine from 4.00 to 2000 ng/mL. During validation, the inter- and intra-day accuracy and precision at the tested QC concentrations (N = 18) for rifapentine were between 97.4% and 100.6%, and 3.1% and 8.3%, respectively. The inter- and intra-day accuracy and precision for 25-O-desacetyl rifapentine were between 96.4% and 106.3%, and 6.7% and 11.8%, respectively. No significant matrix effects were observed, and the method was shown to be specific for rifapentine and 25-O-desacetyl rifapentine. Human milk samples (N = 22) generated during a phase I/II clinical trial were successfully analysed for rifapentine and 25-O-desacetyl rifapentine using this validated method. Concentrations for rifapentine and 25-O-desacetyl rifapentine in human milk samples (N = 22) ranged from 11.2-1180 ng/mL and 7.11-573 ng/mL, respectively.

Pharmacokinetics and Safety of 3 Months of Weekly Rifapentine and Isoniazid for Tuberculosis Prevention in Pregnant Women.

BACKGROUND: Pregnancy increases the risk of tuberculosis and its complications. A 3-month regimen of weekly isoniazid and rifapentine (3HP) is safe and effective for tuberculosis prevention in adults and children, including those with HIV, but 3HP has not been evaluated in pregnancy. METHODS: IMPAACT 2001 was a phase I/II trial evaluating the pharmacokinetics and safety of 3HP among pregnant women with indications for tuberculosis preventative therapy in Haiti, Kenya, Malawi, Thailand, and Zimbabwe (NCT02651259). Isoniazid and rifapentine were provided at standard doses (900 mg/week). Pharmacokinetic sampling was performed with the first (second/third trimester) and twelfth (third trimester/postpartum) doses. Nonlinear mixed-effects models were used to estimate drug population pharmacokinetics. RESULTS: Of 50 participants, 20 had HIV and were taking efavirenz-based antiretroviral therapy. Among women without HIV, clearance of rifapentine was 28% lower during pregnancy than postpartum (1.20 vs 1.53 L/hour, P < .001), with area under the concentration-time curve (AUCSS) of 786 and 673 mg × hour/L, respectively. In pregnant women with HIV, clearance was 30% higher than women without HIV (P < .001), resulting in lower AUCss (522 mg × hour/L); clearance did not change significantly between pregnancy and postpartum. Pregnancy did not impact isoniazid pharmacokinetics. There were no drug-related serious adverse events, treatment discontinuations, or tuberculosis cases in women or infants. CONCLUSIONS: 3HP does not require dose adjustment in pregnancy. Rifapentine clearance is higher among women with HIV, but all women achieved exposures of rifapentine and isoniazid associated with successful tuberculosis prevention. The data support proceeding with larger safety-focused studies of 3HP in pregnancy. CLINICAL TRIALS REGISTRATION: ClinicalTrials.gov, NCT02651259.

Association of Maternal Inflammation During Pregnancy With Birth Outcomes and Infant Growth Among Women With or Without HIV in India.

Importance: The association of elevated levels of specific inflammatory markers during pregnancy with adverse birth outcomes and infant growth could indicate pathways for potential interventions. Objective: To evaluate whether higher levels of certain inflammatory markers during pregnancy are associated with preterm birth (PTB), low birth weight (LBW), and infant growth deficits. Design, Setting, and Participants: In this cohort study of pregnant women with or without HIV, 218 mother-infant pairs were followed up from pregnancy through 12 months post partum from June 27, 2016, to December 9, 2019. Pregnant women aged 18 to 40 years and between 13 and 34 weeks of gestation who were receiving antenatal care were enrolled in a cohort stratified by HIV status; sampling was based on convenience sampling from women receiving antenatal care at Byramjee Jeejeebhoy Government Medical College. Exposures: Levels of multiple circulating inflammation markers during the third trimester of pregnancy. Main Outcomes and Measures: The primary study outcome was PTB (<37 weeks' gestation). Secondary outcomes were LBW (<2500 g) and repeated measures (delivery; 6 weeks post partum; and 3, 6, and 12 months post partum using multivariable generalized linear models) of infant growth outcomes (length-for-age, weight-for-age, and weight-for-length z scores). Results: The median age of the 218 women at enrollment was 23 years (IQR, 21-27 years). In multivariable models, higher pregnancy levels of interleukin 17A were associated with increased odds of both PTB (adjusted odds ratio [aOR], 2.62; 95% CI, 1.11-6.17) and LBW (aOR, 1.81; 95% CI, 1.04-3.15). Higher levels of interleukin 1ß were associated with increased PTB (aOR, 1.47; 95% CI, 1.15-1.89) and infant growth deficits (lower length-for-age z score: adjusted ß = -0.10; 95% CI, -0.18 to -0.01; lower weight-for-age z score: adjusted ß = -0.07; 95% CI, -0.14 to 0.001). Conclusions and Relevance: This study suggests that increased levels of certain systemic inflammatory markers, including interleukin 1ß and interleukin 17A, during pregnancy were associated with adverse birth outcomes and infant growth deficits. Future studies should evaluate whether potential interventions to modulate specific inflammatory pathways during pregnancy could improve birth outcomes and infant growth.

Sex-Related Differences in Clinical Presentation and Risk Factors for Mortality in Patients Hospitalized With Coronavirus Disease 2019 in New York City.

We evaluated sex-related differences in symptoms and risk factors for mortality in 4798 patients hospitalized with coronavirus disease 2019 in New York City. When adjusted for age and comorbidities, being male was an independent predictor of death with mortality significantly higher than females, even with low severe acute respiratory syndrome coronavirus 2 viral load at admission.

Impact of HIV status on systemic inflammation during pregnancy.

OBJECTIVE: There are limited studies on the association of HIV infection with systemic inflammation during pregnancy. DESIGN: A cohort study (N = 220) of pregnant women with HIV (N = 70) (all on antiretroviral therapy) and without HIV (N = 150) were enrolled from an antenatal clinic in Pune, India. METHODS: The following systemic inflammatory markers were measured in plasma samples using immunoassays: soluble CD163 (sCD163), soluble CD14 (sCD14), intestinal fatty acid-binding protein (I-FABP), C-reactive protein (CRP), alpha 1-acid glycoprotein (AGP), interferon-ß (IFNß), interferon-γ (IFNγ), interleukin (IL)-1ß, IL-6, IL-13, IL-17A, and tumor necrosis factor α (TNFα). Generalized estimating equation (GEE) and linear regression models were used to assess the association of HIV status with each inflammatory marker during pregnancy and by trimester, respectively. RESULTS: Pregnant women with HIV had higher levels of markers for gut barrier dysfunction (I-FABP), monocyte activation (sCD14) and markers of systemic inflammation (IL-6 and TNFα), but surprisingly lower levels of AGP, an acute phase protein, compared with pregnant women without HIV, with some trimester-specific differences. CONCLUSION: Our data show that women with HIV had higher levels of markers of gut barrier dysfunction, monocyte activation and systemic inflammation. These markers, some of which are associated with preterm birth, might help explain the increase in adverse birth outcomes in women with HIV and could suggest targets for potential interventions.

Validation of New Interactive Nutrition Assistant - Diet in India Study of Health (NINA-DISH) FFQ with multiple 24-h dietary recalls among pregnant women in Pune, India.

Adequate dietary intake is critical to prevent adverse pregnancy outcomes. India has a high burden of maternal and child morbidity and mortality, but there is a lack of adequate tools to assess dietary intake. We validate an FFQ, New Interactive Nutrition Assistant - Diet in India Study of Health (NINA-DISH), among pregnant women living with and without HIV in Pune, India. Women were selected from a cohort study investigating immune responses to HIV and latent tuberculosis during pregnancy. The FFQ was administered during the third trimester and validated against multiple 24-h dietary recalls (24-HDR) collected in second and third trimesters. Data for analysis were available from fifty-eight women out of seventy enrolled into this sub-study, after excluding those with incomplete data or implausible energy intake. The median (Q1, Q3) age of study participants was 23 (20, 25) years. Median (Q1, Q3) daily energy intakes were 10 552 (8000, 11 958) and 10 673 (8510, 13 962) kJ by 24-HDR and FFQ, respectively, with FFQ overestimating nutrient intake. Pearson correlations between log-transformed estimates from FFQ and 24-HDR for energy, protein, carbohydrate, fat, Fe and Zn were 0·47, 0·48, 0·45, 0·33, 0·4 and 0·54, respectively. Energy-adjusted and de-attenuated correlations ranged from 0·41 (saturated fat) to 0·73 (Na). The highest misclassification into extreme tertiles was observed for fat (22 %), saturated fat (21 %) and Na (21 %). Bias existed at higher intake levels as observed by Bland-Altman plots. In conclusion, NINA-DISH is a valid and feasible tool for estimating dietary intakes among urban pregnant women in Western India.

Effects of Pregnancy and Isoniazid Preventive Therapy on Mycobacterium tuberculosis Interferon Gamma Response Assays in Women With HIV.

BACKGROUND: Pregnancy is accompanied by immune suppression. We hypothesized that Mycobacterium tuberculosis-specific inflammatory responses used to identify latent tuberculosis infection (LTBI) lose positivity during pregnancy. We also hypothesized that isoniazid preventive therapy (IPT) may revert LTBI diagnoses because of its sterilizing activity. METHODS: 944 women with human immunodeficiency virus infection (HIV) participating in a randomized, double-blind, placebo-controlled study comparing 28 weeks of IPT antepartum versus postpartum, were tested by QuantiFERON-gold-in-tube (QGIT) antepartum and by QGIT and tuberculin skin test (TST) at delivery and postpartum. Serial QGIT positivity was assessed by logistic regression using generalized estimating equations. RESULTS: From entry to delivery, 68 (24%) of 284 QGIT-positive women reverted to QGIT-negative or indeterminate. Of these, 42 (62%) recovered QGIT positivity postpartum. The loss of QGIT positivity during pregnancy was explained by decreased interferon gamma (IFNγ) production in response to TB antigen and/or mitogen. At delivery, LTBI was identified by QGIT in 205 women and by TST in 113 women. Corresponding numbers postpartum were 229 and 122 women. QGIT and TST kappa agreement coefficients were 0.4 and 0.5, respectively. Among QGIT-positive women antepartum or at delivery, 34 (12%) reverted to QGIT-negative after IPT. There were no differences between women who initiated IPT antepartum or postpartum. CONCLUSIONS: Decreased IFNγ responses in pregnancy reduced QGIT positivity, suggesting that this test cannot reliably rule out LTBI during pregnancy. TST was less affected by pregnancy, but had lower positivity compared to QGIT at all time points. IPT was associated with loss of QGIT positivity, the potential clinical consequences of which need to be investigated.

Association of Vegetable and Animal Flesh Intake with Inflammation in Pregnant Women from India.

In pregnant women, studies are lacking on the relationship of vegetable and animal flesh (poultry, red meat and seafood) intake with inflammation, especially in low- and middle-income countries. We conducted a cohort study of pregnant women receiving antenatal care at BJ Medical College in Pune, India. The dietary intake of pregnant women was queried in the third trimester using a validated food frequency questionnaire. Twelve inflammatory markers were measured in plasma samples using immunoassays. Only 12% of the study population were vegetarians, although animal flesh intake levels were lower compared to Western populations. In multivariable models, higher intakes of total vegetables were associated with lower levels of the T-helper (Th) 17 cytokine interleukin (IL)-17a (p = 0.03) and the monocyte/macrophage activation marker soluble CD163 (sCD163) (p = 0.02). Additionally, higher intakes of poultry were negatively associated with intestinal fatty-acid binding protein (I-FABP) levels (p = 0.01), a marker of intestinal barrier dysfunction and Th2 cytokine IL-13 (p = 0.03), and higher seafood was associated with lower IL-13 (p = 0.005). Our data from pregnant women in India suggest that a higher quality diet emphasizing vegetables and with some animal flesh is associated with lower inflammation. Future studies should confirm these findings and test if modulating vegetables and animal flesh intake could impact specific aspects of immunity and perinatal health.

Sex Differences in CMV Replication and HIV Persistence During Suppressive ART.

BACKGROUND: The association between subclinical cytomegalovirus (CMV) replication and HIV persistence has not been investigated in cis-gender women with HIV. METHODS: Fifty virologically suppressed female participants with HIV were prospectively enrolled and provided oral, vaginal, and urine samples and peripheral blood mononuclear cells at 1 cross-sectional time point. CMV DNA was quantified in each specimen by real-time polymerase chain reaction (PCR). Cellular HIV DNA and HIV RNA transcripts (unspliced and multiply spliced [ms] encoding tat-rev) were quantified by droplet digital (dd) PCR in peripheral blood cells. Forty-nine male individuals with HIV and CMV (historical data) were used as controls. RESULTS: Levels of cellular HIV DNA and unspliced HIV RNA were not different between sexes, but female participants had less detectable msHIV RNA and CMV DNA compared with males (both P < .01). Unlike previously described for males, the presence of CMV DNA was not associated with increased HIV DNA in females. Among female participants, premenopausal status was independently associated with lower HIV DNA compared with postmenopause, after adjusting for nadir CD4 count (P < .01). CONCLUSIONS: Female participants with HIV had reduced cellular HIV RNA and less subclinical CMV DNA compared with males but overall similar HIV DNA levels in our study. Postmenopausal status was independently associated with higher HIV DNA levels among female participants.