Development of shortened HIV-related stigma scales for young people living with HIV and young people affected by HIV in India.

BACKGROUND: HIV-related stigma is associated with poor quality of life and poor healthcare-seeking behaviours in young people living with HIV (YPLHIV) and young people affected by HIV (YPAHIV). India has an estimated 120,000 YPLHIV and 4 million YPAHIV, but efforts to measure HIV-related stigma in them are sparse, impeded by the lack of measuring instruments. Here, we describe the development of the Pune HIV-Stigma Scale (PHSS) and modified-PHSS to measure HIV-related stigma among YPLHIV and YPAHIV, respectively, in India. METHODS: We used data from a mental health study for YPLHIV and YPAHIV aged 15-25 years, conducted at Byramjee Jeejeebhoy Government Medical College & Sassoon General Hospitals, Pune, India, between August 2018 and June 2021. Findings from multiple confirmatory factor analyses and cognitive interviews guided the development of the 12-item PHSS. The modified-PHSS was developed by confirming the structure of the PHSS for YPAHIV. Convergent validity with Center for Epidemiological Studies Depression (CES-D) and UCLA Loneliness scales was assessed using Spearman's correlation coefficients. RESULTS: Model fit indices were good for both the PHSS (χ2 = 65.0, df = 48, p value: 0.052; root mean square error of approximation (RMSEA): 0.054; comparative fit index (CLI): 0.980; Tucker-Lewis index (TLI): 0.972; and standardized root mean square residual (SRMR): 0.067), and the modified-PHSS (χ2 = 56.9, df = 48, p value: 0.176; RMSEA: 0.045; CLI: 0.983; TFI: 0.976, and SRMR: 0.078). Spearman's correlation coefficients indicated low to moderate convergent validity (ρ: 0.03-0.52) across different subscales of the PHSS and modified-PHSS. Cronbach's alpha for the PHSS was 0.82 and for the modified-PHSS 0.81. CONCLUSION: We developed the first scales to measure HIV-related stigma among YPLHIV and YPAHIV in India. These concise scales can facilitate measurement of HIV-related stigma more frequently in research studies. We recommend that they be tested in different Indian languages.

Mullen Scales of Early Learning Adaptation for Assessment of Indian Children and Application to Tuberculous Meningitis.

INTRODUCTION: Tuberculous meningitis (TBM) results in significant morbidity and mortality among children worldwide. Associated neurocognitive complications are common but not well characterized. The Mullen Scales of Early Learning (MSEL), a well-established measure for assessment of neurodevelopment, has not yet been adapted for use in India. This study's goal was to adapt the MSEL for local language and culture to assess neurocognition among children in India, and apply the adapted measure for assessment of children with TBM. METHODS: Administration of MSEL domains was culturally adapted. Robust translation procedures for instructions took place for three local languages: Marathi, Hindi and Tamil. Multilingual staff compared instructions against the original version for accuracy. The MSEL stimuli and instructions were reviewed by psychologists and pediatricians in India to identify items concerning for cultural bias. RESULTS: MSEL stimuli unfamiliar to children in this setting were identified and modified within Visual Reception, Fine-Motor, Receptive Language and Expressive Language Scales. Item category was maintained for adaptations of items visually or linguistically different from those observed in daily life. Adjusted items were administered to six typically developing children to determine modification utility. Two children diagnosed with confirmed TBM (ages 11 and 29 months) were evaluated with the adapted MSEL before receiving study medications. Skills were below age-expectation across visual reception, fine motor and expressive language domains. CONCLUSIONS: This is the first study to assess children with TBM using the MSEL adapted for use in India. Future studies in larger groups of Indian children are warranted to validate the adapted measure.

Willingness to Take Multidrug-resistant Tuberculosis (MDR-TB) Preventive Therapy Among Adult and Adolescent Household Contacts of MDR-TB Index Cases: An International Multisite Cross-sectional Study.

BACKGROUND: Household contacts (HHCs) of individuals with multidrug-resistant tuberculosis (MDR-TB) are at high risk of infection and subsequent disease. There is limited evidence on the willingness of MDR-TB HHCs to take MDR-TB preventive therapy (MDR TPT) to decrease their risk of TB disease. METHODS: In this cross-sectional study of HHCs of MDR-TB and rifampicin-resistant tuberculosis (RR-TB) index cases from 16 clinical research sites in 8 countries, enrollees were interviewed to assess willingness to take a hypothetical, newly developed MDR TPT if offered. To identify factors associated with willingness to take MDR TPT, a marginal logistic model was fitted using generalized estimating equations to account for household-level clustering. RESULTS: From 278 MDR-TB/RR-TB index case households, 743 HHCs were enrolled; the median age of HHCs was 33 (interquartile range, 22-49) years, and 62% were women. HHC willingness to take hypothetical MDR TPT was high (79%) and remained high even with the potential for mild side effects (70%). Increased willingness was significantly associated with current employment or schooling (adjusted odds ratio [aOR], 1.83 [95% confidence interval {CI}, 1.07-3.13]), appropriate TB-related knowledge (aOR, 2.22 [95% CI, 1.23-3.99]), confidence in taking MDR TPT (aOR, 7.16 [95% CI, 3.33-15.42]), and being comfortable telling others about taking MDR TPT (aOR, 2.29 [95% CI, 1.29-4.06]). CONCLUSIONS: The high percentage of HHCs of MDR-TB/RR-TB index cases willing to take hypothetical MDR TPT provides important evidence for the potential uptake of effective MDR TPT when implemented. Identified HHC-level variables associated with willingness may inform education and counseling efforts to increase HHC confidence in and uptake of MDR TPT.

Lipid mediators of inflammation and Resolution in individuals with tuberculosis and tuberculosis-Diabetes.

Individuals with concurrent tuberculosis (TB) and Type 2 diabetes (DM) have a higher risk of adverse outcomes. To better understand potential immunological differences, we utilized a comprehensive panel to characterize pro-inflammatory and pro-resolving (i.e., mediators involved in the resolution of inflammation) lipid mediators in individuals with TB and TB-DM. A nested cross-sectional study of 40 individuals (20 newly diagnosed DM and 20 without DM) was conducted within a cohort of individuals with active drug-susceptible treatment-naïve pulmonary TB. Lipid mediators were quantified in serum samples through lipid mediator profiling. We conducted correlation-based analysis of these mediators. Overall, the arachidonic acid-derived leukotriene and prostaglandin families were the most abundant pro-inflammatory lipid mediators, while lipoxins and maresins families were the most abundant pro-resolving lipid mediators in individuals with TB and TB-DM. Individuals with TB-DM had increased correlations and connectivity with both pro-inflammatory and pro-resolving lipid mediators compared to those with TB alone. We identified the most abundant lipid mediator metabolomes in circulation among individuals with TB and TB-DM; in addition, our data shows a substantial number of significant correlations between both pro-inflammatory and pro-resolving lipid mediators in individuals with TB-DM, delineating a molecular balance that potentially defines this comorbidity.

Acceptability and feasibility of a behavioral and mobile health intervention (COMBIND) shown to increase uptake of prevention of mother to child transmission (PMTCT) care in India.

BACKGROUND: A cluster-randomized trial recently demonstrated that an integrated behavioral and mobile technology intervention improved uptake of key components of a Prevention of Mother to Child Transmission (PMTCT) Option B+ program, among HIV- infected pregnant/breastfeeding women in India. To guide scale-up and optimize programmatic implementation, we conducted a mixed-methods evaluation of the feasibility and acceptability of this intervention. METHODS: The COMmunity Home Based INDia (COMBIND) study, was conducted in four districts of Maharashtra, India and randomized 119 integrated counseling and testing centers (ICTC) and their outreach workers (ORWs) to the COMBIND intervention, an integrated mHealth application that allowed digital data capture, PMTCT educational videos, SMS alerts for missed visits and reminder for visits, combined with personal empowerment and motivational interviewing training for ORWs. This qualitative evaluation was done through 15 in-depth interviews (IDIs) with ORWs and 15 IDIs with HIV-infected pregnant/breastfeeding women from the intervention arm. Utilizing a concurrent nested mixed-method evaluation approach, we assess the feasibility and acceptability of the study intervention. RESULTS: All 30 participants reported that the PMTCT videos were essential in providing easy to understand information on critical aspects of HIV and necessary care related to PMTCT practices. A majority of the ORWs reported that the personal empowerment training with motivational interviewing skills training increased their confidence, motivation and gave them the tools for effectively supporting their clients. The mHealth application improved their working style as it facilitated targeted PMTCT information support, systemized data capture, streamlined their health education delivery practice and provided a sense of work satisfaction. The SMS appointment alerts improved retention in HIV care for mother and baby to the smaller proportion that had access to their phones. Despite reported improvements in knowledge and communication, few ORWs reported that structural challenges such as limited drug stocks, lack of HIV kits or unavailability of trained staff at ICTC, may hamper the uptake of PMTCT services, thus resulting in limited significant impacts of COMBIND on PMTCT outcomes. CONCLUSION: This study found that COMBIND intervention is scalable, feasible, beneficial and very well accepted by ORWs and patients, however structural challenges in goods and services remain.

The burden of anxiety among people living with HIV during the COVID-19 pandemic in Pune, India.

INTRODUCTION: Globally, India has the third largest population of people living with HIV (PLHIV) and the second highest number of COVID-19 cases. Anxiety is associated with antiretroviral therapy (ART) nonadherence. It is crucial to understand the burden of anxiety and its sources among Asian Indian PLHIV during the COVID pandemic, but data are limited. METHODS: During the first month of government mandated lockdown, we administered an anxiety assessment via telephone among PLHIV registered for care at a publicly funded antiretroviral therapy (ART) center in Pune, India. Generalized anxiety was defined as GAD-7 score ≥ 10. Sociodemographic and clinical variables were compared by anxiety status (GAD-7 score ≥ 10 vs GAD-7 score < 10). Qualitative responses to an open-ended question about causes of concern were evaluated using thematic analysis. RESULTS: Among 167 PLHIV, median age was 44 years (IQR 40-50); the majority were cisgender women (60%) and had a monthly family income < 200 USD (81%). Prior history of tuberculosis and other comorbidities were observed in 38 and 27%, respectively. Overall, prevalence of generalized anxiety was 25% (n = 41). PLHIV with GAD-7 score ≥ 10 had fewer remaining doses of ART than those with lower GAD-7 scores (p = 0.05). Thematic analysis indicated that concerns were both health related and unrelated, and stated temporally. Present concerns were often also projected as future concerns. CONCLUSIONS: The burden of anxiety was high during COVID lockdown in our population of socioeconomically disadvantaged PLHIV in Pune and appeared to be influenced by concerns about ART availability. The burden of anxiety among PLHIV will likely increase with the worsening pandemic in India, as sources of anxiety are expected to persist. We recommend the regular use of short screening tools for anxiety to monitor and triage patients as an extension of current HIV services.

The association of household fine particulate matter and kerosene with tuberculosis in women and children in Pune, India.

OBJECTIVES: Household air pollution (HAP) is a risk factor for respiratory disease, however has yet to be definitively associated with tuberculosis (TB). We aimed to assess the association between HAP and TB. METHODS: A matched case-control study was conducted among adult women and children patients with TB and healthy controls matched on geography, age and sex. HAP was assessed using questionnaires for pollution sources and 24-hour household concentrations of particulate matter <2.5 µm in diameter (PM2.5). RESULTS: In total, 192 individuals in 96 matched pairs were included. The median 24-hour time-weighted average PM2.5 was nearly seven times higher than the WHO's recommendation of 25 µg/m3, and did not vary between controls (179 µg/m3; IQR: 113-292) and cases (median 157 µg/m3; 95% CI 93 to 279; p=0.57). Reported use of wood fuel was not associated with TB (OR 2.32; 95% CI 0.65 to 24.20) and kerosene was significantly associated with TB (OR 5.49, 95% CI 1.24 to 24.20) in adjusted analysis. Household PM2.5 was not associated with TB in univariate or adjusted analysis. Controlling for PM2.5 concentration, kerosene was not significantly associated with TB, but effect sizes ranged from OR 4.30 (95% CI 0.78 to 30.86; p=0.09) to OR 5.49 (0.82 to 36.75; p=0.08). CONCLUSIONS: Use of kerosene cooking fuel is positively associated with TB in analysis using reported sources of exposure. Ubiquitously high levels of particulates limited detection of a difference in household PM2.5 between cases and controls.

Elevated highly sensitive C-reactive protein and d-dimer levels are associated with food insecurity among people living with HIV in Pune, India.

OBJECTIVE: To assess the prevalence and determinants of food insecurity among people living with HIV (PLWH) in Pune, India and its association with biomarkers known to confer increased risks of morbidity and mortality in this population. DESIGN: Cross-sectional analysis assessing food insecurity using the standardized Household Food Insecurity Access Scale. Participants were dichotomized into two groups: food insecure and food secure. Logistic regression models were used to assess associations between socio-economic, demographic, clinical, biochemical factors and food insecurity. SETTING: Antiretroviral therapy (ART) centre of Byramjee Jeejeebhoy Government Medical College and Sassoon General Hospitals (BJGMC-SGH), Pune, a large publicly funded tertiary and teaching hospital in western India.ParticpantsAdult (≥18 years) PLWH attending the ART centre between September 2015 and May 2016 who had received ART for either ≤7d (ART-naïve) or ≥1 year (ART-experienced). RESULTS: Food insecurity was reported by 40 % of 483 participants. Independent risk factors (adjusted OR; 95 % CI) included monthly family income <INR 5000 (~70 USD; 13·2; CI 5·4, 32·2) and consuming ≥4 non-vegetarian meals per week (4·7; 1·9, 11·9). High-sensitivity C-reactive protein (hs-CRP) ≥0·33 mg/dl (1·6; 1·04, 2·6) and d-dimer levels 0·19-0·31 µg/ml (1·6; 1·01, 2·6) and ≥0·32 µg/ml (1·9; 1·2, 3·2) were also associated with food insecurity. CONCLUSIONS: More than a third of the study participants were food insecure. Furthermore, higher hs-CRP and d-dimer levels were associated with food insecurity. Prospective studies are required to understand the relationship between food insecurity, hs-CRP and d-dimer better.

Intestinal Barrier Dysfunction and Microbial Translocation in Human Immunodeficiency Virus-Infected Pregnant Women Are Associated With Preterm Birth.

Background: Preterm birth (PTB) rates are high in human immunodeficiency virus (HIV)-infected populations, even when on treatment. Still, only a subset of all births in HIV-infected pregnant women result in PTB, suggesting that risk factors other than HIV infection itself are also important. Inflammation is a known risk factor in uninfected populations, but its role in HIV-infected population have not been studied; in addition, the immune pathways involved are not clear and noninvasive immune markers with predictive value are lacking. Our objective was to determine the association of select markers of inflammation with PTB in HIV-1-infected pregnant women. Methods: Within a randomized trial of pregnant women receiving nevirapine (Six-Week Extended-Dose Nevirapine [SWEN] trial), we nested a case-control study (n = 107; 26 cases, 81 controls) to determine the association of maternal inflammation with PTB. Cases were defined as PTB (<37 weeks' gestational age). We assessed inflammation by measuring plasma levels of markers of general inflammation (C-reactive protein [CRP]), intestinal barrier dysfunction (intestinal fatty acid binding protein [I-FABP]), and microbial translocation/monocyte activation (soluble CD14 [sCD14] and CD163 [sCD163]). Multivariable logistic regression was used to determine the odds of PTB per log2 increase of each marker. Results: In multivariable models, there was increased odds of PTB per unit increase of log2 sCD14 (adjusted odds ratio [aOR], 2.45; 95% confidence interval [CI], 1.24-4.86), log2 sCD163 (aOR, 3.87; 95% CI, 1.43-10.49), and log2 I-FABP (aOR, 2.28; 95% CI, 1.18-4.41) but not log2 CRP (aOR, 0.72; 95% CI, .48-1.09). Conclusions: Our results show that select immune markers can identify women at higher risk for PTB in HIV-1-infected populations and suggest that modulating gut barrier integrity and microbial translocation may affect PTB. Clinical Trials Registration: NCT00061321.

Addressing knowledge gaps and prevention for tuberculosis-infected Indian adults: a vital part of elimination.

BACKGROUND: India plans to eliminate tuberculosis (TB) by 2025, and has identified screening and prevention as key activities. Household contacts (HHCs) of index TB cases are a high-risk population that would benefit from rapid implementation of these strategies. However, best practices for TB prevention and knowledge gaps among HHCs have not been studied. We evaluated TB knowledge and understanding of prevention among tuberculin skin-test (TST) positive HHCs. While extensive information is available in other high-burden settings regarding TB knowledge gaps, identifying how Indian adult contacts view their transmission risk and prevention options may inform novel screening algorithms and education efforts that will be part of the new elimination plan. METHODS: We approached adult HHC to administer a questionnaire on TB knowledge and understanding of infection. Over 1 year, 100 HHC were enrolled at a tertiary hospital in Pune, India. RESULTS: The study population was 61% (n = 61) female, with a mean age of 36.6 years (range 18-67, SD = 12). Education levels were high, with 78 (78%) having at least a high school education, and 23 (24%) had at least some college education. Four (4%) of our participants were HIV-infected. General TB knowledge among HHC was low, with a majority of participants believing that you can get TB from sharing dishes (70%) or touching something that has been coughed on (52%). Understanding of infection was also low, with 42% believing that being skin-test positive means you have disease. To assess readiness for preventive therapy, we asked participants whether they are at a higher risk of progressing to active disease because of their LTBI status. Fifty-four (55%) felt that they are at higher risk. Only 8% had heard of preventive therapy. CONCLUSION: Our TB knowledge survey among HHCs with evidence of recent exposure found that knowledge is poor and families are confused about transmission in the household. It is imperative that the Indian program develop tools and incentives that can be used to educate TB cases and their families on what infected HHCs can do to prevent disease, including preventive therapy.

Drug-resistant Enterobacteriaceae colonization is associated with healthcare utilization and antimicrobial use among inpatients in Pune, India.

BACKGROUND: Healthcare exposure may increase drug-resistant Enterobacteriaceae colonization risk. Nascent antimicrobial stewardship efforts in low- and middle-income countries require setting-specific data. We aimed to evaluate risk factors for inpatient drug resistant Enterobacteriaceae colonization in a resource-limited setting in India. METHODS: Patients age ≥ 6 months admitted with ≥24 h of fever to a tertiary hospital in Pune, India were enrolled in a prospective cohort. Perirectal swabs, collected on admission and hospitalization day 3 or 4, were cultured in vancomycin- and ceftriaxone-impregnated media to assess for ceftriaxone-resistant Enterobacteriaceae (CTRE) and carbapenem-resistant Enterobacteriaceae (CPRE). Multivariable analyses assessed risk factors for drug-resistant Enterobacteriaceae colonization among participants without admission colonization. RESULTS: Admission perirectal swabs were collected on 897 participants; 87 (10%) had CTRE and 14 (1.6%) had CPRE colonization. Admission CTRE colonization was associated with recent healthcare contact (p < 0.01). Follow-up samples were collected from 620 participants, 67 (11%) had CTRE and 21 (3.4%) had CPRE colonization. Among 561 participants without enrollment CTRE colonization, 49 (9%) participants were colonized with CTRE at follow-up. Detection of CTRE colonization among participants not colonized with CTRE at admission was independently associated with empiric third generation cephalosporin treatment (adjusted odds ratio [OR] 2.9, 95% CI 1.5-5.8). Follow-up transition to CPRE colonization detection was associated with ICU admission (OR 3.0, 95% CI 1.0-8.5). CONCLUSIONS: Patients who receive empiric third generation cephalosporins and are admitted to the ICU rapidly develop detectable CTRE and CPRE colonization. Improved antimicrobial stewardship and infection control measures are urgently needed upon hospital admission.

Gender-based violence screening methods preferred by women visiting a public hospital in Pune, India.

BACKGROUND: Gender-based violence (GBV) is a major global public health concern and is a risk factor for adverse health outcomes. Early identification of GBV is crucial for improved health outcomes. Interactions with health care providers may provide a unique opportunity for routine GBV screening, if a safe, confidential environment can be established. METHODS: Between November 2014 and February 2015, a cross-sectional, observational study was conducted where women were interviewed about their opinions concerning GBV screening in a tertiary health care setting in Pune, India. Trained counsellors interviewed 300 women at different out-patient and in-patient departments using a semi-structured questionnaire. RESULTS: Twenty-three percent of these women reported experiencing GBV in their life. However, 90% of women said they had never been asked about GBV in a health care setting. Seventy-two percent expressed willingness to be asked about GBV by their health care providers, with the preferred provider being nurses or counsellors. More than half (53%) women reported face-to-face interview as the most preferred method for screening. There were no major differences in these preferences by GBV history status. CONCLUSIONS: Our study provides evidence for preferred GBV screening methods and optimal provider engagement as perceived by women attending a public hospital.

Maternal Syphilis: An Independent Risk Factor for Mother to Infant Human Immunodeficiency Virus Transmission.

Syphilis is associated with increased human immunodeficiency virus acquisition and sexual transmission; we examined impact on human immunodeficiency virus mother-to-child transmission among mother-infant pairs enrolled in the India Six-Week Extended-Dose Nevirapine study. Maternal syphilis, diagnosed serologically using Venereal Disease Research Laboratory titer plus Treponema Pallidum Hemagglutination Assay, was associated with 2.5-fold greater risk.

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

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.

Pharmaceutical cost dynamics for the treatment of rifampicin-resistant tuberculosis in children and adolescents in South Africa, India, and the Philippines.

Rifampicin-resistant (RR) tuberculosis (TB) in children is a major global health concern but is often neglected in economics research. Accurate cost estimations across the spectrum of paediatric RR-TB treatment regimens are critical inputs for prioritisation and budgeting decisions, and an existing knowledge gap at local and international levels. This normative cost analysis was nested in a Phase I/II pharmacokinetics, safety, tolerability, and acceptability trial of TB medications in children in South Africa, the Philippines and India. It assessed the pharmaceutical costs of 36 childhood RR-TB regimens using combinations from 16 different medicines in 34 oral formulations (adult and child-friendly) in 11 weight bands in children <15 years of age. The analysis used local and Global Drug Facility pricing, and local and international guideline recommendations, including adaptions of BPaL and BPaLM regimens in adults. Costs varied significantly between regimen length, age/weight banding, severity of disease, presence of fluroquinolone resistance, and different country guideline recommendations. WHO recommended regimen costs ranged 12-fold: from US$232 per course (short regimen in non-severe disease) to US$2,761 (long regimen in severe, fluroquinolone-resistant disease). Regimen treating fluoroquinolone-resistant infection cost US$1,090 more than comparable WHO-recommended regimen. Providing child-friendly medicine formulations in <5-year-olds across all WHO-recommended regimens is expected to cost an additional $380 (range $212-$563) per child but is expected to have wider benefits including palatability, acceptability, adherence, tolerability, and dose accuracy. There were substantial differences in regimen affordability between countries when adjusted for purchasing power and domestic spending on health. Appropriate, effective, and affordable treatment options are an important component of the fight against childhood RR-TB. A comprehensive understanding of the cost and affordability dynamics of treatment options will enable national TB programs and global collaborations to make the best use of limited healthcare resources for the care of children with RR-TB.

Self-reported Antiretroviral Adherence: Association With Maternal Viral Load Suppression in Postpartum Women Living With HIV-1 From Promoting Maternal and Infant Survival Everywhere, a Randomized Controlled Trial in Sub-Saharan Africa and India.

INTRODUCTION: Optimal adherence to antiretroviral therapy (ART) is crucial to promoting maternal-infant health. SETTING: Fourteen sites in 7 countries within sub-Saharan Africa and India. METHODS: The multicomponent, open-label strategy PROMISE trial enrolled breastfeeding mother-infant pairs not meeting in-country criteria for maternal ART (mART) initiation in the postpartum component within 5 days of delivery. Randomization was to mART versus infant NVP (iNVP) prophylaxis. Infants in the mART arm also received 6 weeks of iNVP. Self-reported adherence was assessed in a secondary analysis. Time-to-event analyses were performed to explore the association between adherence and maternal viral load (mVL) in the mART arm. RESULTS: Two thousand four hundred thirty-one mother-infant pairs were enrolled between 2011 and 2014; the baseline maternal median CD4 was 686 (IQR 553-869), and the median mVL was 322 copies/mL (IQR 40-1422). Self-reported adherence was lower in the mART arm compared with the iNVP arm (no missed doses within 4 weeks of all study visits: 66% vs 83%; within 2 weeks: 71% vs 85%; P < 0.0001). The iNVP adherence at week 6 was high in both arms: 97% in mART arm; 95% in iNVP arm. Time-to-event analyses showed that adherence to mART was associated with time to first mVL ≥400 copies/mL ( P < 0.0001). Missing 1 full day of doses over 3 days was associated with a 66% risk of mVL ≥1000 copies/mL (HR: 1.66; 95% CI: 1.37, 1.99). CONCLUSIONS: Postpartum women were less adherent to their own ART than mothers providing their infant's nevirapine prophylaxis. The self-reported missed mART doses were associated with high mVL. Strategies to optimize postpartum mART adherence are urgently needed. CLINICAL TRIAL NUMBER: ClinicalTrials.gov: NCT01061151; closed to follow-up.

"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.

Vitamin D deficiency is common among HIV-infected breastfeeding mothers in Pune, India, but is not associated with mother-to-child HIV transmission.

A recent report from Tanzania demonstrated an increased risk of being HIV infected or of dying at birth among children born to breastfeeding mothers with low baseline vitamin D levels. We conducted a nested case-control study among HIV-infected pregnant women in western India to confirm the association between maternal vitamin D levels and mother-to-child transmission (MTCT) of HIV. Vitamin D insufficiency and deficiency were common among HIV-infected pregnant women, but were not associated with mother to child HIV transmission at 1 year postpartum (adjusted odds ratio [AOR], 0.66; 95% CI, 0.30-1.45; P = .30).

Maternal tuberculosis: a risk factor for mother-to-child transmission of human immunodeficiency virus.

BACKGROUND: Maternal human immunodeficiency virus (HIV) RNA load, CD4 cell count, breast-feeding, antiretroviral use, and malaria are well-established factors associated with mother-to-child transmission (MTCT) of HIV; the role of maternal tuberculosis (TB), however, has not been well established. METHODS: The study population was 783 HIV-infected Indian mother-infant pair participants in randomized and ancillary HIV-infected cohorts of the Six Week Extended-Dose Nevirapine (SWEN) Study, a study comparing extended nevirapine versus single-dose nevirapine, to reduce MTCT of HIV among breast-fed infants. Using multivariable logistic regression, we assessed the impact of maternal TB occurring during pregnancy and through 12 months after delivery on risk of MTCT. RESULTS: Of 783 mothers, 3 had prevalent TB and 30 had incident TB at 12 months after delivery. Of 33 mothers with TB, 10 (30%) transmitted HIV to their infants in comparison with 87 of 750 mothers without TB (12%; odds ratio [OR], 3.31; 95% confidence interval [CI], 1.53-7.29; P = .02). In multivariable analysis, maternal TB was associated with 2.51-fold (95% CI, 1.05-6.02; P = .04) increased odds of HIV transmission adjusting for maternal factors (viral load, CD4 cell count, and antiretroviral therapy) and infant factors (breast-feeding duration, infant nevirapine administration, gestational age, and birth weight) associated with MTCT of HIV. CONCLUSIONS: Maternal TB is associated with increased MTCT of HIV. Prevention of TB among HIV-infected mothers should be a high priority for communities with significant HIV/TB burden.