Global emergency medicine: four part series : Paper 4: Global EM education and professionalization.

In 2018, the Canadian Association of Emergency Physicians (CAEP) academic symposium included developing recommendations on supporting global emergency medicine (EM) in Canadian departments and divisions. Members of CAEP's Global EM committee created a four-part series to be published in CJEM that would build upon the symposium recommendations. The objective is to offer practical tools to EM physicians interested in becoming involved in Global EM, as well as provide departments with successful Canadian case examples that foster, facilitate, and grow Global EM efforts. This submission is the fourth paper of the series which focuses on education and continuing professional development for Global EM. It includes resources for resident global EM electives, fellowship training and ongoing or additional CPD training for practicing EM physicians. It also highlights the importance of pre-departure training and other required elements of engaging responsibly in Global EM work.

RéSUMé: En 2018, le symposium universitaire de l'Association canadienne des médecins d'urgence (ACMU) comprenait l'élaboration de recommandations sur le soutien de la médecine d'urgence mondiale (MU) dans les départements et divisions canadiens. Les membres du comité mondial de la GU de l'ACMU proposent une série de quatre articles qui seront publiés dans la MCEM et qui s'appuieront sur les recommandations du symposium. L'objectif est d'offrir des outils pratiques aux médecins en GU qui souhaitent s'impliquer dans la GU mondiale, ainsi que de fournir aux départements des exemples de cas canadiens réussis qui favorisent, facilitent et développent les efforts en GU mondiale. Ce mémoire est le quatrième article de la série qui se concentre sur l'éducation et le développement professionnel continu pour Global EM. Il comprend des ressources pour les cours au choix internationaux de GU des résidents, la formation de fellowship et la formation continue ou supplémentaire de DPC pour les médecins praticiens de GU. Il souligne également l'importance de la formation préalable au départ et d'autres éléments requis pour s'engager de manière responsable dans le travail de gestion des urgences à l'échelle mondiale.

Hospital admission from the emergency department for selected emergent diagnoses during the first year of the COVID-19 pandemic in Ontario: a retrospective population-based study.

BACKGROUND: Avoidance of care during the pandemic may have contributed to delays in care, and as a result, worse patient outcomes. We evaluated markers of illness acuity on presentation to the emergency department among patients with non-COVID-19-related emergent diagnoses and associated outcomes. METHODS: We conducted a retrospective study using linked administrative data from Ontario. We selected 4 emergent diagnoses, namely appendicitis, ectopic pregnancy, renal failure and diabetic ketoacidosis. We used the nonemergent diagnosis of cellulitis as a control. Our primary outcome of interest was hospital admission. Secondary outcomes were ambulance arrival, surgical intervention, subsequent hospital admission within 30 days of discharge from the emergency department or hospital and 30-day mortality. We compared outcomes during the first year of the COVID-19 pandemic (Mar. 15-Dec. 31, 2020) with a control period (Mar. 15-Dec. 31, 2018, and Mar. 15-Dec. 31, 2019). RESULTS: Emergency department visits for all conditions initially decreased during the pandemic. During this period, patients across all study diagnoses were more likely to arrive to the emergency department via ambulance. Patients with an ectopic pregnancy had higher odds of surgery in the pandemic period (odds ratio [OR] 1.27, 95% confidence interval [CI] 1.04-1.55) but this was not observed among patients with appendicitis. Patients with renal failure had increased odds of hospital admission (OR 1.14, 95% CI 1.04-1.24) and 30-day mortality (OR 1.17, 95% CI 1.04-1.31) during the pandemic period. INTERPRETATION: The pandemic period was associated with increased arrival to the emergency department via ambulance across all study diagnoses. Although patients with renal failure had increased hospital admission and death, and patients with ectopic pregnancy had an increased risk of surgery, there were no differences in outcomes for other populations, suggesting the health care system was able to care for these patients effectively.

Comparing methods to classify admitted patients with SARS-CoV-2 as admitted for COVID-19 versus with incidental SARS-CoV-2: A cohort study.

INTRODUCTION: Not all patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection develop symptomatic coronavirus disease 2019 (COVID-19), making it challenging to assess the burden of COVID-19-related hospitalizations and mortality. We aimed to determine the proportion, resource utilization, and outcomes of SARS-CoV-2 positive patients admitted for COVID-19, and assess the impact of using the Center for Disease Control's (CDC) discharge diagnosis-based algorithm and the Massachusetts state department's drug administration-based classification system on identifying admissions for COVID-19. METHODS: In this retrospective cohort study, we enrolled consecutive SARS-CoV-2 positive patients admitted to one of five hospitals in British Columbia between December 19, 2021 and May 31,2022. We completed medical record reviews, and classified hospitalizations as being primarily for COVID-19 or with incidental SARS-CoV-2 infection. We applied the CDC algorithm and the Massachusetts classification to estimate the difference in hospital days, intensive care unit (ICU) days and in-hospital mortality and calculated sensitivity and specificity. RESULTS: Of 42,505 Emergency Department patients, 1,651 were admitted and tested positive for SARS-CoV-2, with 858 (52.0%, 95% CI 49.6-54.4) admitted for COVID-19. Patients hospitalized for COVID-19 required ICU admission (14.0% versus 8.2%, p<0.001) and died (12.6% versus 6.4%, p<0.001) more frequently compared with patients with incidental SARS-CoV-2. Compared to case classification by clinicians, the CDC algorithm had a sensitivity of 82.9% (711/858, 95% CI 80.3%, 85.4%) and specificity of 98.1% (778/793, 95% CI 97.2%, 99.1%) for COVID-19-related admissions and underestimated COVID-19 attributable hospital days. The Massachusetts classification had a sensitivity of 60.5% (519/858, 95% CI 57.2%, 63.8%) and specificity of 78.6% (623/793, 95% CI 75.7%, 81.4%) for COVID-19-related admissions, underestimating total number of hospital and ICU bed days while overestimating COVID-19-related intubations, ICU admissions, and deaths. CONCLUSION: Half of SARS-CoV-2 hospitalizations were for COVID-19 during the Omicron wave. The CDC algorithm was more specific and sensitive than the Massachusetts classification, but underestimated the burden of COVID-19 admissions. TRIAL REGISTRATION: Clinicaltrials.gov, NCT04702945.

Pioneering family physicians and the mechanisms for strengthening primary health care in India-A qualitative descriptive study.

India has one of the most unequal healthcare systems globally, lagging behind its economic development. Improved primary care and primary health care play an integral role in overcoming health disparities. Family medicine is a subset of primary care-delivered by family physicians, characterized by comprehensive, continuous, coordinated, collaborative, personal, family and community-oriented services-and may be able to fill these gaps. This research aims to understand the potential mechanisms by which family physicians can strengthen primary health care. In this qualitative descriptive study, we interviewed twenty family physicians, identified by purposeful and snowball sampling, who are among the first family physicians in India who received accredited certification in FM and were identified as pioneers of family medicine. We used the Contribution of Family Medicine to Strengthening Primary Health Care Framework to understand the potential mechanisms by which family medicine strengthens primary health care. Iterative inductive techniques were used for analysis. This research identifies multiple ways family physicians can strengthen primary health care in India. They are skilled primary care providers and support mid and low-level health care providers' ongoing training and capacity building. They develop relationships with specialists, ensure appropriate referral systems are in place, and, when necessary, work with governments and organizations to access the essential resources needed to deliver care. They motivate the workforce and change how care is delivered by ensuring providers' skills match the needs of communities and engage communities as partners in healthcare delivery. These findings highlight multiple mechanisms by which family physicians strengthen primary health care. Investments in postgraduate training in family medicine and integrating family physicians into the primary care sector, particularly the public sector, could address health disparities.

The emergence of family medicine in India-A qualitative descriptive study.

Countries globally are introducing family medicine to strengthen primary health care; however, for many, that process has been slow. Understanding the implementation of family medicine in a national context is complex but critical to uncovering what worked, the challenges faced, and how the process can be improved. This study explores how family medicine was implemented in India and how early cohort family physicians supported the field's emergence. In this qualitative descriptive study, we interviewed twenty family physicians who were among the first in India and recognized as pioneers. We used Rogers's Diffusion of Innovation Theory to describe and understand the roles of family physicians, as innovators and early adopters, in the process of implementation. Greenhalgh's Model of Diffusion in Service Organizations is applied to identify barriers and enablers to family medicine implementation. This research identifies multiple mechanisms by which pioneering family physicians supported the implementation of family medicine in India. They were innovators who developed the first family medicine training programs. They were early adopters willing to enter a new field and support spread as educators and mentors for future cohorts of family physicians. They were champions who developed professional organizations to bring together family physicians to learn from one another. They were advocates who pushed the medical community, governments, and policymakers to recognize family medicine's role in healthcare. Facilitators for implementation included the supportive environment of academic institutions and the development of family medicine professional organizations. Barriers to implementation included the lack of government support and awareness of the field by society, and tension with subspecialties. In India, the implementation of family medicine has primarily occurred through pioneering family physicians and supportive educational institutions. For family medicine to continue to grow and have the intended impacts on primary care, government and policymaker support are needed.

Risk factors for stunting in children who are HIV-exposed and uninfected after Option B+ implementation in Malawi.

Evidence suggests children HIV-exposed and uninfected (CHEU) experience poor growth. We analysed child anthropometrics and explored factors associated with stunting among Malawian CHEU. Mothers with HIV and their infants HIV-exposed were enroled in a nationally representative prospective cohort within the National Evaluation of Malawi's Prevention of Mother-to-Child HIV Transmission Programme after Option B+ implementation (2014-2018). Anthropometry was measured at enrolment (age 1-6 months), visit 1 (approximately 12 months), and visit 2 (approximately 24 months). Weight-for-age (WAZ) and length-for-age (LAZ) z-scores were calculated using World Health Organization Growth Standards; underweight and stunting were defined as WAZ and LAZ more than 2 standard deviations below the reference median. Multivariable logistic regression restricted to CHEU aged 24 months (±3 months) was used to identify factors associated with stunting. Among 1211 CHEU, 562/1211 attended visit 2, of which 529 were aged 24 months (±3 months) and were included. At age 24 months, 40.4% of CHEU were stunted and/or underweight, respectively. In multi-variable analysis, adjusting for child age and sex, the odds of stunting were higher among CHEU with infectious disease diagnosis compared to those with no diagnosis (adjusted odds ratio = 3.35 [95% confidence interval: 1.82-6.17]), which was modified by co-trimoxazole prophylaxis (p = 0.028). Infant low birthweight was associated with an increased odds of stunting; optimal feeding and maternal employment were correlated with reduced odds. This is one of the first studies examining CHEU growth since Option B+. Interventions to improve linear growth among CHEU should address their multi-faceted health risks, alongside maternal ART prescription, and follow-up of mother-child pairs.

Derivation and validation of a clinical decision rule to risk-stratify COVID-19 patients discharged from the emergency department: The CCEDRRN COVID discharge score.

Objective: To risk-stratify COVID-19 patients being considered for discharge from the emergency department (ED). Methods: We conducted an observational study to derive and validate a clinical decision rule to identify COVID-19 patients at risk for hospital admission or death within 72 hours of ED discharge. We used data from 49 sites in the Canadian COVID-19 Emergency Department Rapid Response Network (CCEDRRN) between March 1, 2020, and September 8, 2021. We randomly assigned hospitals to derivation or validation and prespecified clinical variables as candidate predictors. We used logistic regression to develop the score in a derivation cohort and examined its performance in predicting short-term adverse outcomes in a validation cohort. Results: Of 15,305 eligible patient visits, 535 (3.6%) experienced the outcome. The score included age, sex, pregnancy status, temperature, arrival mode, respiratory rate, and respiratory distress. The area under the curve was 0.70 (95% confidence interval [CI] 0.68-0.73) in derivation and 0.71 (95% CI 0.68-0.73) in combined derivation and validation cohorts. Among those with a score of 3 or less, the risk for the primary outcome was 1.9% or less, and the sensitivity of using 3 as a rule-out score was 89.3% (95% CI 82.7-94.0). Among those with a score of ≥9, the risk for the primary outcome was as high as 12.2% and the specificity of using 9 as a rule-in score was 95.6% (95% CI 94.9-96.2). Conclusion: The CCEDRRN COVID discharge score can identify patients at risk of short-term adverse outcomes after ED discharge with variables that are readily available on patient arrival.

A biomarker assay to risk-stratify patients with symptoms of respiratory tract infection.

BACKGROUND: Patients who present to an emergency department (ED) with respiratory symptoms are often conservatively triaged in favour of hospitalisation. We sought to determine if an inflammatory biomarker panel that identifies the host response better predicts hospitalisation in order to improve the precision of clinical decision making in the ED. METHODS: From April 2020 to March 2021, plasma samples of 641 patients with symptoms of respiratory illness were collected from EDs in an international multicentre study: Canada (n=310), Italy (n=131) and Brazil (n=200). Patients were followed prospectively for 28 days. Subgroup analysis was conducted on confirmed coronavirus disease 2019 (COVID-19) patients (n=245). An inflammatory profile was determined using a rapid, 50-min, biomarker panel (RALI-Dx (Rapid Acute Lung Injury Diagnostic)), which measures interleukin (IL)-6, IL-8, IL-10, soluble tumour necrosis factor receptor 1 (sTNFR1) and soluble triggering receptor expressed on myeloid cells 1 (sTREM1). RESULTS: RALI-Dx biomarkers were significantly elevated in patients who required hospitalisation across all three sites. A machine learning algorithm that was applied to predict hospitalisation using RALI-Dx biomarkers had a mean±sd area under the receiver operating characteristic curve of 76±6% (Canada), 84±4% (Italy) and 86±3% (Brazil). Model performance was 82±3% for COVID-19 patients and 87±7% for patients with a confirmed pneumonia diagnosis. CONCLUSIONS: The rapid diagnostic biomarker panel accurately identified the need for inpatient care in patients presenting with respiratory symptoms, including COVID-19. The RALI-Dx test is broadly and easily applicable across many jurisdictions, and represents an important diagnostic adjunct to advance ED decision-making protocols.

No Difference in Growth Outcomes up to 24 Months of Age by Duration of Exposure to Maternal Antiretroviral Therapy Among Children Who Are HIV-Exposed and Uninfected in Malawi.

Background: With the implementation of lifelong antiretroviral therapy (ART) for HIV treatment and prevention, the proportion of children exposed to ART in utero from conception is increasing. We estimated the effect of timing of ART exposure on growth of children HIV-exposed and uninfected (CHEU) up to Up to 24 months of age in Malawi. Methods: Data were collected from a prospective cohort of infants HIV-exposed aged 1-6 months (enrollment) and their mothers with HIV enrolled in the National Evaluation of Malawi's Prevention of Mother-to-Child Transmission of HIV Programme (2014-2018). Anthropometry was measured at enrollment, visit 1 (approximately 12 months), and visit 2 (approximately 24 months). Weight-for-age (WAZ) and length-for-age (LAZ) were calculated using the WHO Growth Standards. Multivariable mixed-effects models with linear splines for age were used to examine differences in growth by timing of ART exposure (from conception, first/second trimester, or third trimester/postpartum). Models were adjusted for confounders selected a priori guided by a conceptual framework. Hypothesized interactions and potential mediators were explored, and interactions with splines were included in final models if P < 0.1. Results: A total of 1,206 singleton CHEU and their mothers were enrolled and 563 completed the follow-up through 24 months of age. Moreover, 48% of CHEU were exposed to ART from conception, 40% from first/second trimester, and 12% from third trimester/postpartum. At enrollment, 12% of infants had low birthweight (LBW), 98% had been breastfed in past 7 days, and 57% were enrolled in an HIV care clinic. CHEU growth trajectories demonstrated cohort-wide growth faltering after the age of 12 months. Of 788 and 780 CHEU contributing to WAZ and LAZ multivariable models, respectively, there was no evidence of differences in mean WAZ or LAZ among those exposed from conception or first/second trimester vs. third trimester/postpartum and no evidence of a difference in WAZ or LAZ rate of change by timing of ART exposure (all interactions P > 1.0). Conclusion: Reassuringly, ART exposure from conception was not associated with decreased WAZ or LAZ in CHEU Up 24 months of age. Overall growth trajectories suggest CHEU experience growth faltering after 12 months of age and may need support through and beyond the first 2 years of life.

Effect of a tailored sepsis treatment protocol on patient outcomes in the Tikur Anbessa Specialized Hospital, Ethiopia: results of an interrupted time series analysis.

BACKGROUND: Despite improvement, sepsis mortality rates remain high, with an estimated 11 million sepsis-related deaths globally in 2017 (Rudd et. al, Lancet 395:200-211, 2020). Low- and middle-income countries (LMICs) are estimated to account for 85% of global sepsis mortality; however, evidence for improved sepsis mortality in LMICs is lacking. We aimed to improve sepsis care and outcomes through development and evaluation of a sepsis treatment protocol tailored to the Tikur Anbessa Specialized Hospital Emergency Department, Ethiopia, context. METHODS: We employed a mixed methods design, including an interrupted times series study, pre-post knowledge testing, and process evaluation. The primary outcome was the proportion of patients receiving appropriate sepsis care (blood culture collection before antibiotics and initiation of appropriate antibiotics within 1 h of assessment). Secondary outcomes included time to antibiotic administration, 72-h sepsis mortality, and 90-day all-cause mortality. Due to poor documentation, we were unable to assess our primary outcome and time to antibiotic administration. We used segmented regression with outcomes as binomial proportions to assess the impact of the intervention on mortality. Pre-post knowledge test scores were analyzed using the Student's t-test to compare group means for percentage of scenarios with correct diagnosis. RESULTS: A total of 113 and 300 patients were enrolled in the pre-implementation and post-implementation phases respectively. While age and gender were similar across the phases, a higher proportion (31 vs. 57%) of patients had malignancies in the post-implementation phase. We found a significant change in trend between the phases, with a trend for increasing odds of survival in the pre-implementation phase (OR 1.24, 95% CI 0.98-1.56), and a shift down, with odds of survival virtually flat (OR 0.95, 95% CI. 0.88-1.03) in the post-implementation phases for 72-h mortality, and trends for survival pre- and post-implementation are virtually flat for 90-day mortality. We found no significant difference in pre-post knowledge test scores, with interpretation limited by response rate. Implementation quality was negatively impacted by resource challenges. CONCLUSION: We found no improvement in sepsis outcomes, with a trend for increasing odds of survival lost post-implementation and no significant change in knowledge pre- and post-implementation. Variable availability of resources was the principal barrier to implementation. TRIAL REGISTRATION: Open Science Framework osf.io/ju4ga . Registered June 28, 2017.

Treatments, resource utilization, and outcomes of COVID-19 patients presenting to emergency departments across pandemic waves: an observational study by the Canadian COVID-19 Emergency Department Rapid Response Network (CCEDRRN).

BACKGROUND: Treatment for coronavirus disease 2019 (COVID-19) evolved between pandemic waves. Our objective was to compare treatments, acute care utilization, and outcomes of COVID-19 patients presenting to emergency departments (ED) across pandemic waves. METHODS: This observational study enrolled consecutive eligible COVID-19 patients presenting to 46 EDs participating in the Canadian COVID-19 ED Rapid Response Network (CCEDRRN) between March 1 and December 31, 2020. We collected data by retrospective chart review. Our primary outcome was in-hospital mortality. Secondary outcomes included treatments, hospital and ICU admissions, ED revisits and readmissions. Logistic regression modeling assessed the impact of pandemic wave on outcomes. RESULTS: We enrolled 9,967 patients in 8 provinces, 3,336 from the first and 6,631 from the second wave. Patients in the second wave were younger, fewer met criteria for severe COVID-19, and more were discharged from the ED. Adjusted for patient characteristics and disease severity, steroid use increased (odds ratio [OR] 7.4; 95% confidence interval [CI] 6.2-8.9), and invasive mechanical ventilation decreased (OR 0.5; 95% CI 0.4-0.7) in the second wave compared to the first. After adjusting for differences in patient characteristics and disease severity, the odds of hospitalization (OR 0.7; 95% CI 0.6-0.8) and critical care admission (OR 0.7; 95% CI 0.6-0.9) decreased, while mortality remained unchanged (OR 0.7; 95% CI 0.5-1.1). INTERPRETATION: In patients presenting to cute care facilities, we observed rapid uptake of evidence-based therapies and less use of experimental therapies in the second wave. We observed increased rates of ED discharges and lower hospital and critical care resource use over time. Substantial reductions in mechanical ventilation were not associated with increasing mortality. Advances in treatment strategies created health system efficiencies without compromising patient outcomes. TRIAL REGISTRATION: Clinicaltrials.gov, NCT04702945.

RéSUMé: CONTEXTE: Le traitement de la maladie à coronavirus 2019 (COVID-19) a évolué entre les vagues pandémiques. Notre objectif était de comparer les traitements, l'utilisation des soins aigus et les résultats des patients atteints de la maladie COVID-19 se présentant aux urgences à travers les vagues de pandémie. MéTHODES: Cette étude observationnelle a recruté des patients COVID-19 éligibles consécutifs se présentant à 46 services d'urgence participant au Réseau canadien de réponse rapide aux services d'urgence COVID-19 (CCEDRRN) entre le 1er mars et le 31 décembre 2020. Nous avons recueilli des données au moyen d'un examen rétrospectif des dossiers. Notre principal résultat a été la mortalité à l'hôpital. Les résultats secondaires incluaient les traitements, les admissions à l'hôpital et aux soins intensifs, les revisites aux urgences et les réadmissions. La modélisation par régression logistique a évalué l'impact de la vague de pandémie sur les résultats. RéSULTATS: Nous avons recruté 9 967 patients dans 8 provinces, 3 336 de la première vague et 6 631 de la deuxième vague. Les patients de la deuxième vague étaient plus jeunes, moins nombreux à répondre aux critères de gravité de la COVID-19 et plus nombreux à quitter les urgences. Après ajustement en fonction des caractéristiques des patients et de la gravité de la maladie, le recours aux stéroïdes a augmenté (rapport de cotes [RC] 7.4 ; intervalle de confiance à 95 % [IC] 6.2­8.9) et la ventilation mécanique invasive a diminué (RC 0.5 ; IC à 95 % 0.4­0.7) lors de la deuxième vague par rapport à la première. Après ajustement pour tenir compte des différences dans les caractéristiques des patients et la gravité de la maladie, les probabilités d'hospitalisation (RC 0.7 ; IC à 95 % 0.6­0.8) et d'admission en soins intensifs (RC 0.7 ; IC à 95 % 0.6­0.9) ont diminué, tandis que la mortalité est restée inchangée (RC 0.7 ; IC à 95 % 0.5­1.1). INTERPRéTATION: Chez les patients se présentant dans les établissements de soins de santé, nous avons observé une adoption rapide des thérapies fondées sur des données probantes et un moindre recours aux thérapies expérimentales lors de la deuxième vague. Nous avons observé une augmentation des taux de sortie des services d'urgence et une diminution de l'utilisation des ressources hospitalières et des soins intensifs au fil du temps. Les réductions substantielles de la ventilation mécanique n'étaient pas associées à une augmentation de la mortalité. Les progrès réalisés dans les stratégies de traitement ont permis d'améliorer l'efficacité des systèmes de santé sans compromettre les résultats pour les patients.

The National Evaluation of Malawi's PMTCT Program (NEMAPP) study: 24-month HIV-exposed infant outcomes from a prospective cohort study.

OBJECTIVES: Data on long-term HIV-free survival in breastfeeding, HIV-exposed infants (HEIs) are limited. The National Evaluation of Malawi's Prevention of Mother-to-Child Transmission (PMTCT) Program (NEMAPP), conducted between 2014 and 2018, evaluated mother-to-child transmission (MTCT) and infant outcomes up to 24 months postpartum. METHODS: We enrolled a nationally representative cohort of HEIs at 54 health facilities across four regional strata in Malawi and used multivariable Cox regression analysis to investigate the risk of adverse outcomes (HIV transmission, infant death and loss to follow-up) to 24 months postpartum. Models, controlling for survey design, were fitted for the total cohort (n = 3462) and for a subcohort that received maternal viral load (VL) monitoring (n = 1282). RESULTS: By 24 months, in 3462 HEIs, weighted cumulative MTCT was 4.9% [95% confidence interval (CI) 3.7-6.4%], 1.3% (95% CI 0.8-2.2%) of HEIs had died, 26.2% (95% CI 24.0-28.6%) had been lost to follow-up and 67.5% (95% CI 65.0-70.0%) were alive and HIV-free. Primiparity [weighted adjusted hazard ratio (aHR) 1.6; 95% CI 1.1-2.2; parity 2-3: weighted aHR 1.5; 95% CI 1.2-1.9], the mother not disclosing her HIV status to her partner (no disclosure: weighted aHR 1.3; 95% CI 1.1-1.6; no partner: weighted aHR 0.7; 95% CI 0.5-0.9), unknown maternal ART start (weighted aHR 2.0; 95% CI 1.0-3.9) and poor adherence (missed ≥ 2 days of ART in the last month: weighted aHR 1.7; 95% CI 1.2-2.2; not on ART: weighted aHR 1.7; 95% CI 1.0-2.7) were associated with adverse outcomes by 24 months. In the subcohort analysis, risk of HIV transmission or infant death was higher among HEIs whose mothers started ART post-conception (during pregnancy: weighted aHR 3.2; 95% CI 1.3-7.7; postpartum: weighted aHR 12.4; 95% CI 1.5-99.6) or when maternal viral load at enrolment was > 1000 HIV-1 RNA copies/mL (weighted aHR 15.7; 95% CI 7.8-31.3). CONCLUSIONS: Infant positivity and infant mortality at 24 months were low for a breastfeeding population. Starting ART pre-conception had the greatest impact on HIV-free survival in HEIs. Further population-level reduction in MTCT may require additional intervention during breastfeeding for women new to PMTCT programmes. Pre-partum diagnosis and linkage to ART, followed by continuous engagement in care during breastfeeding can further reduce MTCT but are challenging to implement.

Early post-partum viremia predicts long-term non-suppression of viral load in HIV-positive women on ART in Malawi: Implications for the elimination of infant transmission.

BACKGROUND: Long-term viral load (VL) suppression among HIV-positive, reproductive-aged women on ART is key to eliminating mother-to-child transmission (MTCT) but few data exist from sub-Saharan Africa. We report trends in post-partum VL in Malawian women on ART and factors associated with detectable VL up to 24 months post-partum. METHODS: 1-6 months post-partum mothers, screened HIV-positive at outpatient clinics in Malawi, were enrolled (2014-2016) with their infants. At enrollment, 12- and 24-months post-partum socio-demographic and PMTCT indicators were collected. Venous samples were collected for determination of maternal VL (limit of detection 40 copies/ml). Results were returned to clinics for routine management. RESULTS: 596/1281 (46.5%) women were retained in the study to 24 months. Those retained were older (p<0.01), had higher parity (p = 0.03) and more likely to have undetectable VL at enrollment than those lost to follow-up (80.0% vs 70.2%, p<0.01). Of 590 women on ART (median 30.1 months; inter-quartile range 26.8-61.3), 442 (74.9%) with complete VL data at 3 visits were included in further analysis. Prevalence of detectable VL at 12 and 24 months was higher among women with detectable VL at enrollment than among those with undetectable VL (74 detectable VL results/66 women vs. 19/359; p<0.001). In multivariable analysis (adjusted for age, parity, education, partner disclosure, timing of ART start and self-reported adherence), detectable VL at 24 months was 9 times more likely among women with 1 prior detectable VL (aOR 9.0; 95%CI 3.5-23.0, p<0.001) and 226 times more likely for women with 2 prior detectable VLs (aOR 226.4; 95%CI 73.0-701.8, p<0.001). CONCLUSIONS: Detectable virus early post-partum strongly increases risk of ongoing post-partum viremia. Due to high loss to follow-up, the true incidence of detectable VL over time is probably underestimated. These findings have implications for MTCT, as well as for the mothers, and call for intensified VL monitoring and targeted adherence support for women during pregnancy and post-partum.