Publications by authors named "Jyoti S Mathad"

20 Publications

  • Page 1 of 1

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

Open Forum Infect Dis 2021 Aug 9;8(8):ofab370. Epub 2021 Jul 9.

Department of Obstetrics and Gynecology, Weill Cornell Medical Center, New York, New York, USA.

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.
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http://dx.doi.org/10.1093/ofid/ofab370DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8344509PMC
August 2021

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

Clin Infect Dis 2021 Jul 29. Epub 2021 Jul 29.

Johns Hopkins University School of Medicine, Baltimore, MD, USA.

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 (900mg weekly). Pharmacokinetic sampling was performed with the first (2 nd/3 rd trimester) and twelfth (3 rd trimester/postpartum) doses. Non-linear 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/h, p<0.001), with area under the concentration-time curve (AUCSS) of 786 and 673 mg*hr/L, respectively. In pregnant women with HIV, clearance was 30% higher than women without HIV (p<0.001), resulting in a lower AUCss (522 mg*h/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 TB 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.
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http://dx.doi.org/10.1093/cid/ciab665DOI Listing
July 2021

Impact of HIV status on systemic inflammation during pregnancy.

AIDS 2021 Jul 8. Epub 2021 Jul 8.

Department of Epidemiology, Columbia University Mailman School of Public Health, New York, USA Department of Medicine, Weill Cornell Medical College, New York, USA Department of Biostatistics, Columbia University Mailman School of Public Health, New York, USA Department of Obstetrics and Gynecology, Byramjee Jeejeebhoy Government Medical College, Pune, India Byramjee-Jeejeebhoy Government Medical college-Johns Hopkins University Clinical Research Site, Pune, India Instituto Goncalo Moniz, Fundação Oswaldo Cruz, Salvador, Brazil Multinational Organization Network Sponsoring Translational and Epidemiological Research, (MONSTER) Initiative, Salvador, Brazil Faculdade de Medicina, Universidade Federal da Bahia, Salvador, Brazil Curso de Medicina, Faculdade de Tecnologia e Ciências, Salvador, Brazil Universidade Salvador (UNIFACS), Laureate Universities, Salvador, Brazil Escola Bahiana de Medicina e Saúde Pública (EBMSP), Salvador, Brazil National Institutes of Health, National Institute for Research in Tuberculosis, International Center for Excellence in Research, Chennai, India Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, USA.

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-β (IFNβ), interferon-γ (IFNγ), interleukin (IL)-1β, 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 to pregnant women without HIV, with some trimester-specific differences.

Conclusions: 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.
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http://dx.doi.org/10.1097/QAD.0000000000003016DOI Listing
July 2021

Systemic Inflammation in Pregnant Women With Latent Tuberculosis Infection.

Front Immunol 2020 27;11:587617. Epub 2021 Jan 27.

Department of Epidemiology, Columbia University Mailman School of Public Health, New York, NY, United States.

Background: Recent studies in adults have characterized differences in systemic inflammation between adults with and without latent tuberculosis infection (LTBI+ . LTBI-). Potential differences in systemic inflammation by LTBI status has not been assess in pregnant women.

Methods: We conducted a cohort study of 155 LTBI+ and 65 LTBI- pregnant women, stratified by HIV status, attending an antenatal clinic in Pune, India. LTBI status was assessed by interferon gamma release assay. Plasma was used to measure systemic inflammation markers using immunoassays: IFN, CRP, AGP, I-FABP, IFN, IL-1, soluble CD14 (sCD14), sCD163, TNF, IL-6, IL-17a and IL-13. Linear regression models were fit to test the association of LTBI status with each inflammation marker. We also conducted an exploratory analysis using logistic regression to test the association of inflammatory markers with TB progression.

Results: Study population was a median age of 23 (Interquartile range: 21-27), 28% undernourished (mid-upper arm circumference (MUAC) <23 cm), 12% were vegetarian, 10% with gestational diabetes and 32% with HIV. In multivariable models, LTBI+ women had significantly lower levels of third trimester AGP, IL1β, sCD163, IL-6 and IL-17a. Interestingly, in exploratory analysis, LTBI+ TB progressors had significantly higher levels of IL1, IL-6 and IL-13 in multivariable models compared to LTBI+ non-progressors.

Conclusions: Our data shows a distinct systemic immune profile in LTBI+ pregnant women compared to LTBI- women. Data from our exploratory analysis suggest that LTBI+ TB progressors do not have this immune profile, suggesting negative association of this profile with TB progression. If other studies confirm these differences by LTBI status and show a causal relationship with TB progression, this immune profile could identify subsets of LTBI+ pregnant women at high risk for TB progression and who can be targeted for preventative therapy.
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http://dx.doi.org/10.3389/fimmu.2020.587617DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7873478PMC
July 2021

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.

Br J Nutr 2021 Oct 28;126(8):1247-1256. Epub 2020 Dec 28.

Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, NY10032, USA.

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.
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http://dx.doi.org/10.1017/S0007114520005188DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8236492PMC
October 2021

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

Nutrients 2020 Dec 8;12(12). Epub 2020 Dec 8.

Department of Epidemiology, Columbia University Mailman School of Public Health, New York, NY 10032, USA.

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 ( = 0.03) and the monocyte/macrophage activation marker soluble CD163 (sCD163) ( = 0.02). Additionally, higher intakes of poultry were negatively associated with intestinal fatty-acid binding protein (I-FABP) levels ( = 0.01), a marker of intestinal barrier dysfunction and Th2 cytokine IL-13 ( = 0.03), and higher seafood was associated with lower IL-13 ( = 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.
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http://dx.doi.org/10.3390/nu12123767DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7762525PMC
December 2020

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

Open Forum Infect Dis 2020 Aug 11;7(8):ofaa289. Epub 2020 Jul 11.

Weill Cornell Medicine, New York, USA.

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  < .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 ( < .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.
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http://dx.doi.org/10.1093/ofid/ofaa289DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7415302PMC
August 2020

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

Clin Infect Dis 2020 Jul 28. Epub 2020 Jul 28.

Departments of Medicine and International Health, Johns Hopkins University, Baltimore, MD.

Background: Pregnancy is accompanied by immune suppression. We hypothesized that M. 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 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 (24%) 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 IFNγ production in response to TB antigen and/or mitogen. At delivery, QGIT identified 205 and TST 113 women with LTBI. 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.
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http://dx.doi.org/10.1093/cid/ciaa1083DOI Listing
July 2020

TB prevention strategies and unanswered questions for pregnant and postpartum women living with HIV: the need for improved evidence.

J Int AIDS Soc 2020 03;23(3):e25481

Department of Medicine and International Health, Johns Hopkins University, Baltimore, MD, USA.

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http://dx.doi.org/10.1002/jia2.25481DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7086302PMC
March 2020

Population Pharmacokinetics of Isoniazid, Pyrazinamide, and Ethambutol in Pregnant South African Women with Tuberculosis and HIV.

Antimicrob Agents Chemother 2020 02 21;64(3). Epub 2020 Feb 21.

Division of Clinical Pharmacology, Department of Medicine, University of Cape Town, Cape Town, South Africa

Tuberculosis is an important cause of maternal morbidity, but little is known about the effects of pregnancy on antituberculosis drug concentrations. We developed population pharmacokinetic models to describe drug dispositions of isoniazid, pyrazinamide, and ethambutol in pregnant women with tuberculosis and HIV. HIV-positive pregnant women with tuberculosis receiving standard first-line tuberculosis treatment and participating in Tshepiso, a prospective cohort study in Soweto, South Africa, underwent sparse pharmacokinetic sampling at >36 weeks of gestation and 7 weeks postpartum. The effects of pregnancy on the pharmacokinetics of isoniazid, pyrazinamide, and ethambutol were investigated via population pharmacokinetic modeling. Isoniazid, pyrazinamide, and ethambutol concentrations were available for 29, 18, and 18 women, respectively. Their median weight was 66 kg while pregnant and 64 kg postpartum. No significant differences were observed in drug clearance, volume of distribution, or bioavailability during and after pregnancy. The model-estimated isoniazid, pyrazinamide, and ethambutol area under the concentration-time curve from 0 to 24 h (AUC) medians were, respectively, 6.88, 419, and 16.5 mg · h/liter during pregnancy versus 5.01, 407, and 19.0 mg · h/liter postpartum. The model-estimated maximum concentration ( ) medians for isoniazid, pyrazinamide, and ethambutol were, respectively, 1.39, 35.9, and 1.82 mg/liter during pregnancy versus 1.43, 34.5, and 2.11 mg/liter postpartum. power calculations determined that our analysis was powered 91.8%, 59.2%, and 90.1% at a  of <0.01 to detect a 40% decrease in the AUCs of isoniazid, pyrazinamide, and ethambutol, respectively. Pregnancy does not appear to cause relevant changes in the exposure to isoniazid, pyrazinamide, and ethambutol. Additional studies of antituberculosis drugs in pregnancy are needed.
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http://dx.doi.org/10.1128/AAC.01978-19DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7038290PMC
February 2020

Female global health leadership: data-driven approaches to close the gender gap.

Lancet 2019 02;393(10171):521-523

Center for Global Health, Department of Medicine, Weill Cornell Medicine, New York, NY 10065, USA; Department of Medicine, Bugando Medical Centre and Catholic University of Health and Allied Sciences, Mwanza, Tanzania.

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http://dx.doi.org/10.1016/S0140-6736(19)30203-XDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7391058PMC
February 2019

Screening and diagnosis of gestational diabetes in India: a systematic review and meta-analysis.

Acta Diabetol 2018 Jun 26;55(6):613-625. Epub 2018 Mar 26.

Departments of Medicine and OB-GYN, Weill Cornell Medicine, New York, NY, USA.

Aims: Although diabetes is rapidly increasing in India, there is no national consensus on best practices for screening, diagnosis, and management of gestational diabetes mellitus (GDM). The goal of this study was to systematically review the literature for studies reporting the prevalence and screening and diagnostic methods for gestational diabetes in India.

Methods: We searched MEDLINE, Embase, and POPLINE for studies on screening for GDM in India. We included English-language full reports and conference abstracts of cross-sectional studies, prospective, and retrospective cohorts that reported the screening method and prevalence of GDM. We performed descriptive analysis on all studies and meta-analysis, meta-regression, and subgroup meta-analysis on studies with medium or low risk of bias.

Results: We included 64 studies reporting 90 prevalence estimates. Prevalence estimates ranged from 0 to 41.9%. Subset meta-analyses showed that the IADPSG diagnostic criteria found significantly more GDM cases (prevalence = 19.19% [15.5, 23.6], p < 0.05) than the WHO 1999 criteria (10.13% [8.17, 12.50]) and DIPSI criteria (7.37% [5.2, 10.16]). Studies that compared the IADPSG and WHO 1999 criteria showed poor positive agreement (33-79%). Studies specifying time of GDM diagnosis showed that patients (11-60%) develop GDM as early as the first trimester, but many GDM cases (16-40%) are missed if screened only at first visit.

Conclusions: In India, prevalence estimates of GDM vary substantially by diagnostic criteria. When evaluating screening and diagnostic criteria for GDM, providers should consider their patients' needs and correlate screening criteria with pregnancy outcomes.
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http://dx.doi.org/10.1007/s00592-018-1131-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5999405PMC
June 2018

Pulmonary Infections in Pregnancy.

Semin Respir Crit Care Med 2017 04 22;38(2):174-184. Epub 2017 May 22.

Department of Medicine and International Health, Johns Hopkins University, Center for Clinical Global Health Education, Baltimore, Maryland.

Pregnant women experience physiological and immunological changes that increase the risk or severity of certain pulmonary infections. These changes also affect drug disposition, which impacts treatment choices. In this article, we review the available data on (1) the physiological and immunological changes that specifically impact tuberculosis, influenza, and varicella pneumonia; (2) active and latent tuberculosis management, including drug monitoring and maternal–infant outcomes; (3) the treatment and prevention of influenza; and (4) the diagnosis and management of varicella pneumonia. Clinical trials often exclude pregnant women, but there is a consensus that treating pregnant women for tuberculosis, influenza, and varicella pneumonia improves outcomes for both the woman and her child.
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http://dx.doi.org/10.1055/s-0037-1602375DOI Listing
April 2017

Sex-Related Differences in Inflammatory and Immune Activation Markers Before and After Combined Antiretroviral Therapy Initiation.

J Acquir Immune Defic Syndr 2016 10;73(2):123-9

*Division of Infectious Diseases, Center for Global Health, Weill Cornell Medical College, New York, NY; †Johns Hopkins Clinical Trials Unit, Byramjee Jeejeebhoy Government Medical College, Pune, India; ‡Division of Infectious Diseases, Johns Hopkins University School of Medicine, Baltimore, MD; §Division of Infectious Diseases, Department of Internal Medicine, University of California Davis Medical Center, Sacramento, CA; ‖Department of Medicine, University of Zimbabwe College of Health Sciences, Harare, Zimbabwe; ¶Division of Infectious Diseases, Hospital Nossa Senhora de Conceição, Porto Alegre, Brazil; #Les Centres GHESKIO, Port-Au-Prince, Haiti; **Department of Medicine, University of North Carolina-Lilongwe, Lilongwe, Malawi; ††Research Institute for Health Sciences, Chiang Mai, Thailand; ‡‡Impacta Peru, San Miguel, Peru; §§Durban International Clinical Research Site, Durban University of Technology, Durban, South Africa; ‖‖STD/AIDS Clinical Research Laboratory, Instituto de Pesquisa Clinica Evandro Chagas, Fundacao Oswaldo Cruz, Rio de Janeiro, Brazil; ¶¶Department of Medicine, University of Witwatersrand, Johannesburg, South Africa; ##National AIDS Research Institute (ICMR), Pune, India; ***Malawi College of Medicine-Johns Hopkins University Research Project, Blantyre, Malawi; †††YRGCARE Medical Center, Chennai, India; ‡‡‡Investigative Medicine Branch, Laboratório Integrado de Microbiologia e Imunorregulação (LIMI), Centro de Pesquisas Gonçalo Moniz (CPqGM), Fundação Oswaldo Cruz (FIOCRUZ), Salvador, Brazil; §§§Division of Infectious Diseases, University of Colorado-Denver, Aurora, CO; ‖‖‖Division of Infectious Diseases, Department of Medicine, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA; and ¶¶¶Division of Infectious Diseases, Northwestern University Feinberg School of Medicine, Chicago, IL.

Background: Women progress to death at the same rate as men despite lower plasma HIV RNA (viral load). We investigated sex-specific differences in immune activation and inflammation as a potential explanation.

Methods: Inflammatory and immune activation markers [interferon γ, tumor necrosis factor (TNF) α, IL-6, IL-18, IFN-γ-induced protein 10, C-reactive protein (CRP), lipopolysaccharide, and sCD14] were measured at weeks 0, 24, and 48 after combination antiretroviral therapy (cART) in a random subcohort (n = 215) who achieved virologic suppression in ACTG A5175 (Prospective Evaluation of Antiretrovirals in Resource-Limited Settings). Association between sex and changes in markers post-cART was examined using random effects models. Average marker differences and 95% confidence intervals were estimated using multivariable models.

Results: At baseline, women had lower median log10 viral load (4.93 vs 5.18 copies per milliliter, P = 0.01), CRP (2.32 vs 4.62 mg/L, P = 0.01), detectable lipopolysaccharide (39% vs 55%, P = 0.04), and sCD14 (1.9 vs 2.3 µg/mL, P = 0.06) vs men. By week 48, women had higher interferon γ (22.4 vs 14.9 pg/mL, P = 0.05), TNF-α (11.5 vs 9.5 pg/mL, P = 0.02), and CD4 (373 vs 323 cells per cubic millimeter, P = 0.02). In multivariate analysis, women had greater increases in CD4 and TNF-α but less of a decrease in CRP and sCD14 compared with men.

Conclusions: With cART-induced viral suppression, women have less reduction in key markers of inflammation and immune activation compared with men. Future studies should investigate the impact of these sex-specific differences on morbidity and mortality.
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http://dx.doi.org/10.1097/QAI.0000000000001095DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5023467PMC
October 2016

Quantitative IFN-γ and IL-2 Response Associated with Latent Tuberculosis Test Discordance in HIV-infected Pregnant Women.

Am J Respir Crit Care Med 2016 06;193(12):1421-8

3 Byramjee Jeejeebhoy Government Medical College-Johns Hopkins Clinical Trials Unit, Pune, India.

Rationale: Pregnant women with latent tuberculosis infection (LTBI) are at high risk for development of TB, especially if infected with HIV.

Objectives: To assess the performance of LTBI tests in pregnant and postpartum women infected with HIV, investigate the immunology behind discordance in pregnancy, and explore the implications for the development of postpartum TB.

Methods: We screened pregnant women in their second/third trimester and at delivery for LTBI using the tuberculin skin test (TST) and IFN-γ release assay (IGRA) (QuantiFERON Gold). A subset of antepartum women had longitudinal testing, with repeat testing at delivery and postpartum and additional cytokines measured from the IGRA supernatant. The kappa statistic and Wilcoxon rank sum test were used to determine agreement and comparison of cytokine concentrations, respectively.

Measurements And Main Results: Of 252 enrolled, 71 (28%) women had a positive IGRA but only 27 (10%) had a positive TST (P < 0.005). There was 75% agreement (kappa, 0.25). When stratified by pregnancy versus delivery, 20% had IGRA(+)/TST(-) discordance at each time point. A positive IGRA was associated with known TB contact (odds ratio, 3.6; confidence interval, 1.2-11.1; P = 0.02). Compared with IGRA(+)/TST(+), women with IGRA(+)/TST(-) discordance had significantly less IFN-γ (1.85 vs. 3.48 IU/ml; P = 0.02) and IL-2 (46.17 vs. 84.03 pg/ml; P = 0.01). Five developed postpartum TB, of which three had IGRA(+)/TST(-) discordance during pregnancy.

Conclusions: Choice of LTBI test in pregnant women infected with HIV affects results. Pregnant women with IGRA(+)/TST(-) discordance had less IFN-γ and IL-2 than those with concordant-positive results and may represent an especially high-risk subset for the development of active TB postpartum.
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http://dx.doi.org/10.1164/rccm.201508-1595OCDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4910889PMC
June 2016

Toward Earlier Inclusion of Pregnant and Postpartum Women in Tuberculosis Drug Trials: Consensus Statements From an International Expert Panel.

Clin Infect Dis 2016 Mar 9;62(6):761-769. Epub 2015 Dec 9.

Department of Bioethics, NIH Clinical Center, Bethesda.

Tuberculosis is a major cause of morbidity and mortality in women of childbearing age (15-44 years). Despite increased tuberculosis risk during pregnancy, optimal clinical treatment remains unclear: safety, tolerability, and pharmacokinetic data for many tuberculosis drugs are lacking, and trials of promising new tuberculosis drugs exclude pregnant women. To advance inclusion of pregnant and postpartum women in tuberculosis drug trials, the US National Institutes of Health convened an international expert panel. Discussions generated consensus statements (>75% agreement among panelists) identifying high-priority research areas during pregnancy, including: (1) preventing progression of latent tuberculosis infection, especially in women coinfected with human immunodeficiency virus; (2) evaluating new agents/regimens for treatment of multidrug-resistant tuberculosis; and (3) evaluating safety, tolerability and pharmacokinetics of tuberculosis drugs already in use during pregnancy and postpartum. Incorporating pregnant women into clinical trials would extend evidence-based tuberculosis prevention and treatment standards to this special population.
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http://dx.doi.org/10.1093/cid/civ991DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4772846PMC
March 2016

Pregnancy differentially impacts performance of latent tuberculosis diagnostics in a high-burden setting.

PLoS One 2014 21;9(3):e92308. Epub 2014 Mar 21.

Byramjee Jeejeebhoy Government Medical College- Johns Hopkins Clinical Trials Unit, Pune, Maharashtra, India; Division of Infectious Diseases, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America.

Background: Targeted screening for latent TB infection (LTBI) in vulnerable populations is a recommended TB control strategy. Pregnant women are at high risk for developing TB and likely to access healthcare, making pregnancy an important screening opportunity in developing countries. The sensitivity of the widely-used tuberculin skin test (TST), however, may be reduced during pregnancy.

Methods: We performed a cross-sectional study comparing the TST with the QuantiFERON Gold In-tube (QGIT) in 401 HIV-negative women presenting antepartum (n = 154), at delivery (n = 148), or postpartum (n = 99) to a government hospital in Pune, India. A subset of 60 women enrolled during pregnancy was followed longitudinally and received both tests at all three stages of pregnancy.

Results: The QGIT returned significantly more positive results than the TST. Of the 401 women in the cross-sectional study, 150 (37%) had a positive QGIT, compared to 59 (14%) for the TST (p<0.005). Forty-nine (12%) did not have their TST read. Of 356 who had both results available, 46 (13%) were concordant positive, 91 (25%) were discordant (12 (3%) TST+/QGIT-; 79 (22%) TST-/QGIT+), and 206 (57%) concordant negative. Comparison by stage of pregnancy revealed that QGIT percent positivity remained stable between antepartum and delivery, unlike TST results (QGIT 31-32% vs TST 11-17%). Median IFN-γ concentration was lower at delivery than in antepartum or postpartum (1.66 vs 2.65 vs 8.99 IU/mL, p = 0.001). During postpartum, both tests had significantly increased positives (QGIT 31% vs 32% vs 52%, p = 0.01; TST 17% vs 11% vs 25%, p<0.005). The same trends were observed in the longitudinal subset.

Conclusions: Timing and choice of LTBI test during pregnancy impact results. QGIT was more stable and more closely approximated the LTBI prevalence in India. But pregnancy stage clearly affects both tests, raising important questions about how the complex immune changes brought on by pregnancy may impact LTBI screening.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0092308PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3962385PMC
January 2015

Maternal pneumococcal capsular IgG antibodies and transplacental transfer are low in South Asian HIV-infected mother-infant pairs.

Vaccine 2014 Mar 30;32(13):1466-72. Epub 2014 Jan 30.

Cincinnati Children's Hospital, Cincinnati, OH, United States.

Background: Our understanding of the mother-to-child transfer of serotype-specific pneumococcal antibodies is limited in non-immunized, HIV-positive women.

Methods: We compared geometric mean antibody concentrations (GMCs), geometric mean transplacental cord:maternal ratios (GMRs) and proportions of samples with protective antibody concentration (≥0.35μg/ml) to serotypes 1, 4, 5, 6B, 9V, 14, 18C, 19F, 23F between 74 HIV-infected and 98 HIV-uninfected mother-infant pairs who had not received pneumococcal immunization in South Asia. Multivariable analysis was performed to assess the influence of HIV on protective antibody concentrations.

Results: HIV-infected mothers and their infants exhibited lower GMCs and GMRs than their uninfected counterparts. This was significant for all serotypes except maternal GMC to serotype 1 and GMR for serotype 6B. In multivariate analysis, HIV was significantly associated with reduced odds of having protective pneumococcal IgG levels; 56-73% reduction for 3 maternal serotypes (4, 5, 23F) and 62-90% reduction for all cord samples except serotype 6B.

Conclusions: Maternal HIV infection is associated with lower levels of maternal pneumococcal antibodies and disproportionately lower cord antibodies, relative to maternal antibodies, suggesting that HIV infection compromises transplacental transfer. Reassessment of maternal and/or infant pneumococcal immunization strategies is needed in HIV-infected women and their infants.
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http://dx.doi.org/10.1016/j.vaccine.2014.01.033DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3975143PMC
March 2014

Tuberculosis in pregnant and postpartum women: epidemiology, management, and research gaps.

Clin Infect Dis 2012 Dec 31;55(11):1532-49. Epub 2012 Aug 31.

Division of Infectious Diseases, Weill Cornell Medical College, New York, New York 10065, USA.

Tuberculosis is most common during a woman's reproductive years and is a major cause of maternal-child mortality. National guidelines for screening and management vary widely owing to insufficient data. In this article, we review the available data on (1) the global burden of tuberculosis in women of reproductive age; (2) how pregnancy and the postpartum period affect the course of tuberculosis; (3) how to screen and diagnose pregnant and postpartum women for active and latent tuberculosis; (4) the management of active and latent tuberculosis in pregnancy and the postpartum period, including the safety of tuberculosis medications; and (5) infant outcomes. We also include data on HIV/tuberculosis coinfection and drug-resistant tuberculosis. Finally, we highlight research gaps in tuberculosis in pregnant and postpartum women.
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http://dx.doi.org/10.1093/cid/cis732DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3491857PMC
December 2012
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