Synthetic Controls for Implementation Science: Opportunities for HIV Program Evaluation Using Routinely Collected Data.

PURPOSE OF REVIEW: HIV service delivery programs are some of the largest funded public health programs in the world. Timely, efficient evaluation of these programs can be enhanced with methodologies designed to estimate the effects of policy. We propose using the synthetic control method (SCM) as an implementation science tool to evaluate these HIV programs. RECENT FINDINGS: SCM, introduced in econometrics, shows increasing utility across fields. Key benefits of this methodology over traditional design-based approaches for evaluation stem from directly approximating pre-intervention trends by weighting of candidate non-intervention units. We demonstrate SCM to evaluate the effectiveness of a public health intervention targeting HIV health facilities with high numbers of recent infections on trends in pre-exposure prophylaxis (PrEP) enrollment. This test case demonstrates SCM's feasibility for effectiveness evaluations of site-level HIV interventions. HIV programs collecting longitudinal, routine service delivery data for many facilities, with only some receiving a time-specified intervention, are well-suited for evaluation using SCM.

Factors Associated with Having both Male and Female Recent Sexual Partnerships Among Men Who Have Sex with Men in Harare and Bulawayo, Zimbabwe.

To better understand male and female sexual partnerships among men who have sex with men (MSM), we used data from a 2019 biobehavioral survey among MSM in Harare and Bulawayo, Zimbabwe to conduct bivariate analyses and multivariable logistic regression to determine whether sociodemographic characteristics and HIV-related factors were associated with having both male and female sexual partnerships within the last 6 months. Of included MSM (N = 1143), 31% reported both male and female partnerships in the last 6 months. Being married/cohabiting (adjusted odds ratio (aOR) = 8.58, 95% confidence interval (CI) = 4.92-14.95) or separated/divorced/widowed (aOR = 1.96, 95% CI = 1.24-3.08) vs. being single, and hazardous alcohol consumption (aOR = 1.58, 95% CI 1.19-2.09) were associated with higher odds of having both male and female recent partnerships. Being aged 35 + vs. 18-24 (aOR = 0.50, 95% CI = 0.31-0.81), condomless receptive anal intercourse at last sex with the main male partner (aOR = 0.43, 95% CI = 0.26-0.74), and positive HIV status (aOR = 0.46, 95% CI = 0.31-0.67) were associated with lower odds of recent male and female partnerships. MSM in Harare who reported harassment/abuse (aOR = 3.16, 95% CI = 1.72-5.79) had higher odds of both male and female partnerships than MSM in Bulawayo reporting harassment/abuse. The prevalence of both male and female recent partnerships (31%) was lower among MSM in this survey than in other biobehavioral surveys of MSM in sub-Saharan Africa. Findings suggest that MSM with recent male and female partnerships compared to MSM with only male recent partners have lower odds of positive HIV status and participate in behaviors that lower HIV risk; however, the direction of these relationships cannot be determined due to the cross-sectional nature of the data. The findings also suggest a possible connection between experiences of stigma of MSM behavior and not having both male and female partnerships that warrants further exploration. Accessible, stigma-free HIV testing and education programming that considers the potential overlap between the MSM and general populations via both male and female partnerships and the associated behaviors could be a key component of HIV elimination in Zimbabwe.

Cross-Coupling of Amines via Photocatalytic Denitrogenation of In Situ Generated Diazenes.

A method for C(sp3)-C(sp3) cross-coupling of amines is described. Primary amines are converted to 1,2-dialkyldiazenes by treatment with O-nosylhydroxylamines in the presence of atmospheric oxygen. Denitrogenation of the diazenes with an iridium photocatalyst then forges the C-C bond. The substrate scope accommodates a broad latitude of functionality, including heteroaromatics and unprotected alcohols and acids.

Effects of the Coronavirus Disease 2019 Pandemic on Human Immunodeficiency Virus Services: Findings from 11 Sub-Saharan African Countries.

BACKGROUND: Due to concerns about the effects of the coronavirus disease 2019 (COVID-19 pandemic on health services, we examined its effects on human immunodeficiency virus (HIV) services in sub-Saharan Africa. METHODS: Quarterly data (Q1, 10/2019-12/2019; Q2, 1/2020-3/2020; Q3, 4/2020-6/2020; Q4, 7/2020-9/2020) from 1059 health facilities in 11 countries were analyzed and categorized by stringency of pandemic measures. We conducted a difference-in-differences assessment of HIV service changes from Q1-Q2 to Q3-Q4 by higher vs lower stringency. RESULTS: There was a 3.3% decrease in the number HIV tested from Q2 to Q3 (572 845 to 553 780), with the number testing HIV-positive declining by 4.9% from Q2 to Q3. From Q3 to Q4, the number tested increased by 10.6% (612 646), with an increase of 8.8% (23 457) in the number testing HIV-positive with similar yield (3.8%). New antiretroviral therapy (ART) initiations declined by 9.8% from Q2 to Q3 but increased in Q4 by 9.8%. Across all quarters, the number on ART increased (Q1, 419 028 to Q4, 476 010). The number receiving viral load (VL) testing in the prior 12 months increased (Q1, 255 290 to Q4, 312 869). No decrease was noted in VL suppression (Q1, 87.5% to Q4, 90.1%). HIV testing (P < .0001) and new ART initiations (P = .001) were inversely associated with stringency. CONCLUSIONS: After initial declines, rebound was brisk, with increases noted in the number HIV tested, newly initiated or currently on ART, VL testing, and VL suppression throughout the period, demonstrating HIV program resilience in the face of the COVID-19 crisis.

Prevalence and psychosocial factors associated with self-injurious thoughts among people living with HIV presenting for HIV testing in Mozambique.

Self-injurious thoughts have been associated with psychiatric morbidity and suicide. Little is known about psychosocial factors associated with self-injurious thoughts among people newly diagnosed with HIV in sub-Saharan Africa. This study examined whether food insufficiency, mental health symptoms, or social support were associated with recent self-injurious thoughts among people newly diagnosed with HIV in Mozambique. The sample included 2001 PLWH aged ≥ 18 newly diagnosed with HIV at 10 health clinics in Mozambique between April 2013 and June 2015. Data were collected at time of HIV diagnosis. Multivariable logistic regression modeled the association of social support, affective mental health symptom severity, somatic mental health symptom severity, and food insufficiency on recent self-injurious thoughts. Ten percent of respondents reported recent self-injurious thoughts, which was higher among women than men (11% vs 7%). In multivariable analyses, food insufficiency [adjusted odds ratio (aOR) 1.7 (95% CI 1.3, 2.2)], and low [aORvs no = 4.8, 95% CI 1.7, 13.4) and moderate/high affective symptom severity [aORvs no = 8.7, 95% CI 2.8, 27.6) were associated with greater odds of self-injurious thoughts. Interventions to address self-injurious thoughts should consider accompanying psychosocial stressors. Longitudinal research to examine mechanisms through which psychosocial stressors are associated with self-injurious thoughts is warranted.

Operationalizing influenza vaccination in an urban safety-net emergency department.

INTRODUCTION: Influenza vaccination is a recommended tool in preventing influenza-related illnesses, medical visits, and hospitalizations. With many patients remaining unvaccinated each year, the Emergency Department (ED) represents a unique opportunity to provide vaccinations to patient not yet vaccinated. However, busy urban safety-net EDs maybe challenged to safely execute such a vaccination program. The aim of this quality improvement project was to assess influenza vaccination feasibility in the ED and improve influenza vaccination rates in our community. METHODS: The quality improvement work-group, comprised of ED physicians, nurses, and pharmacists, designed and implemented an influenza vaccination protocol that aligned with the ED workflow. The outcome measure was the total number of patients vaccinated per month and per influenza season. Process measures included the type of influenza vaccine administered and type of care area within ED. Balancing measures were also included. RESULTS: Following the initiative, a total of 337 patients received influenza vaccinations in the ED between September 1, 2018 and December 31, 2020 compared to none during the previous influenza season. With each influenza season, the number of vaccinated patients increased from 61 to 134 and 142, respectively. The average age of the patients was 48.23 ± 15.29, 52.89 ± 15.91, and 44.92 ± 18.97 years old. Most patients received the vaccination while roomed in the high acuity section of the adult ED. No adverse effects or automated dispensing cabinet stockouts were observed. CONCLUSION: Our structured program indicates that influenza vaccine administration to eligible patients is feasible in a busy urban safety-net ED. Piloting new and further developing existing ED-based influenza vaccination programs have the potential to significantly benefit public health.

Optimizing Differentiated HIV Treatment Models in Urban Zimbabwe: Assessing Patient Preferences Using a Discrete Choice Experiment.

Differentiated service delivery holds great promise for streamlining the delivery of health services for HIV. This study used a discrete choice experiment to assess preferences for differentiated HIV treatment delivery model characteristics among 500 virally suppressed adults on antiretroviral therapy in Harare, Zimbabwe. Treatment model characteristics included location, consultation type, healthcare worker cadre, operation times, visit frequency and duration, and cost. A mixed effects logit model was used for parameter estimates to identify potential preference heterogeneity among participants, and interaction effects were estimated for sex and age as potential sources of divergence in preferences. Results indicated that participants preferred health facility-based services, less frequent visits, individual consultations, shorter waiting times, lower cost and, delivered by respectful and understanding healthcare workers. Some preference heterogeneity was found, particularly for location of service delivery and group vs. individual models; however, this was not fully explained by sex and age characteristics of participants. In urban areas, facility-based models, such as the Fast Track model requiring less frequent clinic visits, are likely to better align with patient preferences than some of the other community-based or group models that have been implemented. As Zimbabwe scales up differentiated treatment models for stable patients, a clear understanding of patient preferences can help in designing services that will ensure optimal utilization and improve the efficiency of service delivery.

RESUMEN: La entrega de servicios diferenciados representa una gran promesa para optimizar la prestación de servicios sanitarios para el VIH. Este estudio utilizó un experimento de elecciones discretas para evaluar las preferencias en cuanto a las características de los modelos diferenciados de prestación de tratamiento para el VIH entre 500 adultos con supresión viral bajo tratamiento antirretroviral en Harare, Zimbabue. Las características de los modelos de tratamientos incluyeron el lugar, el tipo de consulta, la estructura en la que estaba inserto el trabajador sanitario, los tiempos operativos, la frecuencia y duración de las visitas y los costos. Se utilizó un modelo de probabilidad de efectos mixtos para las estimaciones de los parámetros para identificar una posible heterogeneidad en las preferencias entre los participantes, y se estimaron los efectos de las interacciones por el sexo y la edad como fuentes potenciales de diferencia en las preferencias. Los resultados indicaron que los participantes preferían servicios basados en centros de salud, visitas menos frecuentes, consultas individuales, tiempos de espera más cortos y menores costos, proporcionados por trabajadores sanitarios respetuosos y comprensivos. Se hallaron algunas heterogeneidades en las preferencias, particularmente para el lugar de la prestación del servicio y para los modelos grupales frente a individuales; sin embargo, esto no se explicó totalmente por las características de sexo y edad de los participantes. En áreas urbanas, los modelos basados en los centros, como el modelo de atención rápida (Fast Track), que requieren visitas menos frecuentes a la clínica, probablemente concuerden mejor con las preferencias de los pacientes que los otros modelos grupales o comunitarios que se han propuesto. A medida que en Zimbabue se amplíen los modelos de tratamiento diferenciado para los pacientes estables, un claro conocimiento de las preferencias de los pacientes puede ayudar a diseñar servicios que garantizarán una utilización óptima y mejorarán la eficiencia de la prestación de servicios.

A combination intervention strategy to improve linkage to and retention in HIV care following diagnosis in Mozambique: A cluster-randomized study.

BACKGROUND: Concerning gaps in the HIV care continuum compromise individual and population health. We evaluated a combination intervention strategy (CIS) targeting prevalent barriers to timely linkage and sustained retention in HIV care in Mozambique. METHODS AND FINDINGS: In this cluster-randomized trial, 10 primary health facilities in the city of Maputo and Inhambane Province were randomly assigned to provide the CIS or the standard of care (SOC). The CIS included point-of-care CD4 testing at the time of diagnosis, accelerated ART initiation, and short message service (SMS) health messages and appointment reminders. A pre-post intervention 2-sample design was nested within the CIS arm to assess the effectiveness of CIS+, an enhanced version of the CIS that additionally included conditional non-cash financial incentives for linkage and retention. The primary outcome was a combined outcome of linkage to care within 1 month and retention at 12 months after diagnosis. From April 22, 2013, to June 30, 2015, we enrolled 2,004 out of 5,327 adults ≥18 years of age diagnosed with HIV in the voluntary counseling and testing clinics of participating health facilities: 744 (37%) in the CIS group, 493 (25%) in the CIS+ group, and 767 (38%) in the SOC group. Fifty-seven percent of the CIS group achieved the primary outcome versus 35% in the SOC group (relative risk [RR]CIS vs SOC = 1.58, 95% CI 1.05-2.39). Eighty-nine percent of the CIS group linked to care on the day of diagnosis versus 16% of the SOC group (RRCIS vs SOC = 9.13, 95% CI 1.65-50.40). There was no significant benefit of adding financial incentives to the CIS in terms of the combined outcome (55% of the CIS+ group achieved the primary outcome, RRCIS+ vs CIS = 0.96, 95% CI 0.81-1.16). Key limitations include the use of existing medical records to assess outcomes, the inability to isolate the effect of each component of the CIS, non-concurrent enrollment of the CIS+ group, and exclusion of many patients newly diagnosed with HIV. CONCLUSIONS: The CIS showed promise for making much needed gains in the HIV care continuum in our study, particularly in the critical first step of timely linkage to care following diagnosis. TRIAL REGISTRATION: ClinicalTrials.gov NCT01930084.

Effectiveness of a combination strategy for linkage and retention in adult HIV care in Swaziland: The Link4Health cluster randomized trial.

BACKGROUND: Gaps in the HIV care continuum contribute to poor health outcomes and increase HIV transmission. A combination of interventions targeting multiple steps in the continuum is needed to achieve the full beneficial impact of HIV treatment. METHODS AND FINDINGS: Link4Health, a cluster-randomized controlled trial, evaluated the effectiveness of a combination intervention strategy (CIS) versus the standard of care (SOC) on the primary outcome of linkage to care within 1 month plus retention in care at 12 months after HIV-positive testing. Ten clusters of HIV clinics in Swaziland were randomized 1:1 to CIS versus SOC. The CIS included point-of-care CD4+ testing at the time of an HIV-positive test, accelerated antiretroviral therapy (ART) initiation for treatment-eligible participants, mobile phone appointment reminders, health educational packages, and noncash financial incentives. Secondary outcomes included each component of the primary outcome, mean time to linkage, assessment for ART eligibility, ART initiation and time to ART initiation, viral suppression defined as HIV-1 RNA < 1,000 copies/mL at 12 months after HIV testing among patients on ART ≥6 months, and loss to follow-up and death at 12 months after HIV testing. A total of 2,197 adults aged ≥18 years, newly tested HIV positive, were enrolled from 19 August 2013 to 21 November 2014 (1,096 CIS arm; 1,101 SOC arm) and followed for 12 months. The median participant age was 31 years (IQR 26-39), and 59% were women. In an intention-to-treat analysis, 64% (705/1,096) of participants at the CIS sites achieved the primary outcome versus 43% (477/1,101) at the SOC sites (adjusted relative risk [RR] 1.52, 95% CI 1.19-1.96, p = 0.002). Participants in the CIS arm versus the SOC arm had the following secondary outcomes: linkage to care regardless of retention at 12 months (RR 1.08, 95% CI 0.97-1.21, p = 0.13), mean time to linkage (2.5 days versus 7.5 days, p = 0.189), retention in care at 12 months regardless of time to linkage (RR 1.48, 95% CI 1.18-1.86, p = 0.002), assessment for ART eligibility (RR 1.20, 95% CI 1.07-1.34, p = 0.004), ART initiation (RR 1.16, 95% CI 0.96-1.40, p = 0.12), mean time to ART initiation from time of HIV testing (7 days versus 14 days, p < 0.001), viral suppression among those on ART for ≥6 months (RR 0.97, 95% CI 0.88-1.07, p = 0.55), loss to follow-up at 12 months after HIV testing (RR 0.56, 95% CI 0.40-0.79, p = 0.002), and death (N = 78) within 12 months of HIV testing (RR 0.80, 95% CI 0.46-1.35, p = 0.41). Limitations of this study include a small number of clusters and the inability to evaluate the incremental effectiveness of individual components of the combination strategy. CONCLUSIONS: A combination strategy inclusive of 5 evidence-based interventions aimed at multiple steps in the HIV care continuum was associated with significant increase in linkage to care plus 12-month retention. This strategy offers promise of enhanced outcomes for HIV-positive patients. TRIAL REGISTRATION: ClinicalTrials.gov NCT01904994.

Nurse-led HIV services and quality of care at health facilities in Kenya, 2014-2016.

OBJECTIVE: To develop a novel measure to characterize human immunodeficiency virus (HIV) programme quality at health facilities in Kenya and explore its associations with patient- and facility-level characteristics. METHODS: We developed a composite indicator to measure quality of HIV care, comprising: assessment of eligibility for antiretroviral therapy (ART); initiation of ART; and retention on ART or in care, if ineligible for ART, for 12 months. We applied the comprehensive retention indicator to routinely collected clinical data from 13 331 patients enrolled in HIV care and treatment at 63 health facilities in the Eastern and Nyanza regions of Kenya from 1 January 2014 to 31 March 2016. We explored the association between facility- and patient-level characteristics and the primary outcome: appropriate staging and management of HIV, and retention in care over 12 months. FINDINGS: Of the enrolled patients, 8404 (63%) achieved comprehensive retention 12 months after enrolment in care. In univariate analyses, patients at facilities where nurses delivered HIV treatment services (including eligibility assessment, initiation and follow up of ART) had significantly higher comprehensive retention rates at 12 months. In multivariate analyses, after adjusting for both facility- and patient-level characteristics, patients at facilities where nurses initiated ART had significantly higher comprehensive retention in care at 12 months (relative risk, RR: 1.22; 95% confidence interval, CI: 1.00-1.48). CONCLUSION: Nurse-led HIV services were significantly associated with quality of care, confirming the central role of nurses in the achievement of global health goals, and the need for further investment in nursing education, training and mentoring.

Outcomes among HIV-infected children initiating HIV care and antiretroviral treatment in Ethiopia.

OBJECTIVE: To describe pediatric ART scale-up in Ethiopia, one of the 21 global priority countries for elimination of pediatric HIV infection. METHODS: A descriptive analysis of routinely collected HIV care and treatment data on HIV-infected children (<15 years) enrolled at 70 health facilities in four regions in Ethiopia, January 2006-September 2013. Characteristics at enrollment and ART initiation are described along with outcomes at 1 year after enrollment. Among children who initiated ART, cumulative incidence of death and loss to follow-up (LTF) were estimated using survival analysis. RESULTS: 11 695 children 0-14 years were enrolled in HIV care and 6815 (58.3%) initiated ART. At enrollment, 31.2% were WHO stage III and 6.3% stage IV. The majority (87.9%) were enrolled in secondary or tertiary facilities. At 1 year after enrollment, 17.9% of children were LTF prior to ART initiation. Among children initiating ART, cumulative incidence of death was 3.4%, 4.1% and 4.8%, and cumulative incidence of LTF was 7.7%, 11.8% and 16.6% at 6, 12 and 24 months, respectively. Children <2 years had higher risk of LTF and death than older children (P < 0.0001). Children with more advanced disease and those enrolled in rural settings were more likely to die. Children enrolled in more recent years were less likely to die but more likely to be LTF. CONCLUSIONS: Over the last decade large numbers of HIV-infected children have been successfully enrolled in HIV care and initiated on ART in Ethiopia. Retention prior to and after ART initiation remains a major challenge.

Informing efforts to reach UNAIDS' 90-90-90 targets: a comparison of characteristics of people diagnosed with HIV in health facilities to the general population of people living with HIV in Mozambique.

Global targets aim to increase the number of people living with HIV (PLWH) who know their status. Using data from Mozambican facility-based HIV testing and counseling (HTC) and a population-based survey, we compared characteristics of PLWH diagnosed in HTC to the general population of PLWH to identify subgroups that are missing from the health system and may be undiagnosed. Male and female PLWH aged 50+ (PPR = 0.47, p = .0001) and with higher HIV knowledge (PPR = 0.52, p = .004) were underrepresented in HTC. A higher proportion of patients diagnosed in health facilities were aged 25-39 (PPR = 1.23, p = .02). Female PLWH with lower economic (PPR = 0.70, p = .04) and educational status (PPR = 0.86, p = .02) and male PLWH aged 18-24 (PPR = 0.47, p = .03) were underrepresented in HTC. Comparing HTC data to population-based data can inform efforts to increase HIV diagnoses and to ensure that all PLWH know their status.

Characteristics and outcomes of adult Ethiopian patients enrolled in HIV care and treatment: a multi-clinic observational study.

BACKGROUND: We describe trends in characteristics and outcomes among adults initiating HIV care and treatment in Ethiopia from 2006-2011. METHODS: We conducted a retrospective longitudinal analysis of HIV-positive adults (≥ 15 years) enrolling at 56 Ethiopian health facilities from 2006-2011. We investigated trends over time in the proportion enrolling through provider-initiated counseling and testing (PITC), baseline CD4+ cell counts and WHO stage. Additionally, we assessed outcomes (recorded death, loss to follow-up (LTF), transfer, and total attrition (recorded death plus LTF)) before and after ART initiation. Kaplan-Meier techniques estimated cumulative incidence of these outcomes through 36 months after ART initiation. Factors associated with LTF and death after ART initiation were estimated using Hazard Ratios accounting for within-clinic correlation. RESULTS: 93,418 adults enrolled into HIV care; 53,300 (57%) initiated ART. The proportion enrolled through PITC increased from 27.6% (2006-2007) to 44.8% (2010-2011) (p < .0001). Concurrently, median enrollment CD4+ cell count increased from 158 to 208 cells/mm(3) (p < .0001), and patients initiating ART with advanced WHO stage decreased from 56.6% (stage III) and 15.0% (IV) in 2006-2007 to 47.6% (stage III) and 8.5% (IV) in 2010-2011. Median CD4+ cell count at ART initiation remained stable over time. 24% of patients were LTF before ART initiation. Among those initiating ART, attrition was 30% after 36 months, with most occurring within the first 6 months. Recorded death after ART initiation was 6.4% and 9.2% at 6 and 36 months, respectively, and decreased over time. Younger age, male gender, never being married, no formal education, low CD4+ cell count, and advanced WHO stage were associated with increased LTF. Recorded death was lower among younger adults, females, married individuals, those with higher CD4+ cell counts and lower WHO stage at ART initiation. CONCLUSIONS: Over time, enrollment in HIV care through outpatient PITC increased and patients enrolled into HIV care at earlier disease stages across all HIV testing points. However, median CD4+ cell count at ART initiation remained steady. Pre- and post-ART attrition (particularly in the first 6 months) have remained major challenges in ensuring prompt ART initiation and retention on ART.

A combination strategy for enhancing linkage to and retention in HIV care among adults newly diagnosed with HIV in Mozambique: study protocol for a site-randomized implementation science study.

BACKGROUND: Despite the extraordinary scale up of HIV prevention, care and treatment services in sub-Saharan Africa (SSA) over the past decade, the overall effectiveness of HIV programs has been significantly hindered by high levels of attrition across the HIV care continuum. Data from "real-life" settings are needed on the effectiveness of an easy to deliver package of services that can improve overall performance of the HIV care continuum. METHODS/DESIGN: We are conducting an implementation science study using a two-arm cluster site-randomized design to determine the effectiveness of a combination intervention strategy (CIS) using feasible, evidence-based, and practical interventions-including (1) point-of-care (POC) CD4 count testing, (2) accelerated antiretroviral therapy initiation for eligible individuals, and (3) SMS reminders for linkage to and retention in care-as compared to the standard of care (SOC) in Mozambique in improving linkage and retention among adults following HIV diagnosis. A pre-post intervention two-sample design is nested within the CIS arm to assess the incremental effectiveness of the CIS plus financial incentives (CIS + FI) compared to the CIS without FI on study outcomes. Randomization is done at the level of the study site, defined as a primary health facility. Five sites are included from the City of Maputo and five from Inhambane Province. Target enrollment is a total of 2,250 adults: 750 in the SOC arm, 750 in the CIS cohort of the intervention arm and 750 in the CIS + FI cohort of the intervention arm (average of 150 participants per site). Participants are followed for 12 months from time of HIV testing to ascertain a combined endpoint of linkage to care within 1 month after testing and retention in care 12 months from HIV test. Cost-effectiveness analyses of CIS compared to SOC and CIS + FI compared to CIS will also be conducted. DISCUSSION: Study findings will provide evidence on the effectiveness of a CIS and the incremental effectiveness of a CIS + FI in a "real-life" service delivery system in a SSA country severely impacted by HIV. TRIAL REGISTRATION: Clinicaltrials.gov, NCT01930084.

Maximizing Adherence and Minimizing Time to Antibiotics: A Multidisciplinary Institutional Trauma Bay Protocol for Single Antibiotic Prophylaxis in Open Fractures.

OBJECTIVES: To determine if a multidisciplinary institutional protocol can optimize the time to antibiotic (Abx) administration for open fractures (openFx) and improve compliance with the administration of Abx prophylaxis during trauma activation. DESIGN: Retrospective pre-post study design. SETTING: Single Level II Trauma Center. PATIENT SELECTION CRITERIA: All patients who triggered a trauma activation with suspected openFx and were treated according to the institutional single antibiotic regimen were eligible for inclusion. Patients were excluded if fractures did not involve the appendicular skeleton. Patients treated before implementation of a standardized institutional protocol where premixed IV bags of antibiotics were stocked in automated dispensing systems within ED trauma bays (January 2021-October 2022) were defined as the "pre" group and those treated following implementation the "post" group. OUTCOME MEASURES AND COMPARISONS: The primary outcome was time from trauma bay arrival to antibiotic aministration, measured in minutes, with comparisons made between preprotocol and postprotocol implementation. Secondary outcomes for comparison included rates (%) of time to Abx <60 minutes, allergic reactions, acute kidney injury, ototoxicity, surgical site infection, multi-drug-resistant organisms identified in blood or biopsy cultures in cases requiring reoperation, and Clostridium difficile infection in the gastrointestinal system, confirmed by stool test results, within 30 days. RESULTS: Twenty-four patients (mean age 39.5 ± 16.3 years) met the criteria after protocol implementation compared with 72 patients (mean age 34.3 ± 14.8 years) before implementation. Implementation of the institutional protocol resulted in a significant reduction in the time to Abx administration for openFx from 87.9 ± 104.6 minutes to 22.2 ± 12.8 minutes in the postprotocol group ( P < 0.001). In addition, only 53% in the preprotocol group received Abx within 60 minutes compared with 96% in postprotocol group ( P < 0.001). Post hoc power analysis revealed that the study was powered at 92% (effect size = 0.72) to detect a significant difference between the preprotocol and postprotocol groups. CONCLUSION: This study provides evidence that a multidisciplinary institutional protocol for the administration of Abx prophylaxis can be an effective strategy for optimizing the time to Abx administration in cases of suspected openFx. This protocol may be implemented in other trauma centers to optimize time to Abx administration for openFx. LEVEL OF EVIDENCE: Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.

Hepatitis B virus infection (HBV) and HIV-HBV coinfection among men who have sex with men, transgender women, and genderqueer individuals in Harare and Bulawayo Zimbabwe, 2019.

Objectives: To measure HIV and Hepatitis B virus (HBV) prevalence and associated risk behaviors among men who have sex with men (MSM) and transgender women/genderqueer individuals (TGW/GQ) in Zimbabwe. Methods: We conducted a biobehavioral survey using respondent-driven sampling (RDS) among adult MSM and TGW/GQ in Harare and Bulawayo, Zimbabwe in 2019. Participants completed a questionnaire and underwent testing for HIV and HBV. Results: Overall, 1,510 (Harare: 694, Bulawayo 816) participants were enrolled and consented to testing; 3.8 % (58) tested positive for HBV, 22.5 % (339) tested positive for HIV, and 2.2 % (33) tested positive for both HIV and HBV. HBV prevalence was higher among participants with HIV compared to HIV-negative participants (9.7 % vs. 2.1 %, p < 0.0001). Overall, HBV prevalence was not statistically different between MSM and TGW/GQ (3.7 % vs 4.5 %, p = 0.49) nor between Harare and Bulawayo (3.3 % vs 4.3 %, p = 0.33). Conclusions: Our survey demonstrates the prevalence of HBV among MSM and TGW/GQ is lower than other estimates of HBV among MSM in Africa but remains high among our survey population living with HIV highlighting the need to expand HBV testing and treatment services, especially among people with HIV in Zimbabwe.

Reviewing progress: 7 year trends in characteristics of adults and children enrolled at HIV care and treatment clinics in the United Republic of Tanzania.

BACKGROUND: To evaluate the on-going scale-up of HIV programs, we assessed trends in patient characteristics at enrolment and ART initiation over 7 years of implementation. METHODS: Data were from Optimal Models, a prospective open cohort study of HIV-infected (HIV+) adults (≥15 years) and children (<15 years) enrolled from January 2005 to December 2011 at 44 HIV clinics in 3 regions of mainland Tanzania (Kagera, Kigoma, Pwani) and Zanzibar. Comparative statistics for trends in characteristics of patients enrolled in 2005-2007, 2008-2009 and 2010-2011 were examined. RESULTS: Overall 62,801 HIV + patients were enrolled: 58,102(92.5%) adults, (66.5% female); 4,699(7.5%) children.Among adults, pregnant women enrolment increased: 6.8%, 2005-2007; 12.1%, 2008-2009; 17.2%, 2010-2011; as did entry into care from prevention of mother-to-child HIV transmission (PMTCT) programs: 6.6%, 2005-2007; 9.5%, 2008-2009; 12.6%, 2010-2011. WHO stage IV at enrolment declined: 27.1%, 2005-2007; 20.2%, 2008-2009; 11.1% 2010-2011. Of the 42.5% and 29.5% with CD4+ data at enrolment and ART initiation respectively, median CD4+ count increased: 210 cells/µL, 2005-2007; 262 cells/µL, 2008-2009; 266 cells/µL 2010-2011; but median CD4+ at ART initiation did not change (148 cells/µL overall). Stavudine initiation declined: 84.9%, 2005-2007; 43.1%, 2008-2009; 19.7%, 2010-2011.Among children, median age (years) at enrolment decreased from 6.1(IQR:2.7-10.0) in 2005-2007 to 4.8(IQR:1.9-8.6) in 2008-2009, and 4.1(IQR:1.5-8.1) in 2010-2011 and children <24 months increased from 18.5% to 26.1% and 31.5% respectively. Entry from PMTCT was 7.0%, 2005-2007; 10.7%, 2008-2009; 15.0%, 2010-2011. WHO stage IV at enrolment declined from 22.9%, 2005-2007, to 18.3%, 2008-2009 to 13.9%, 2010-2011. Proportion initiating stavudine was 39.8% 2005-2007; 39.5%, 2008-2009; 26.1%, 2010-2011. Median age at ART initiation also declined significantly. CONCLUSIONS: Over time, the proportion of pregnant women and of adults and children enrolled from PMTCT programs increased. There was a decline in adults and children with advanced HIV disease at enrolment and initiation of stavudine. Pediatric age at enrolment and ART initiation declined. Results suggest HIV program maturation from an emergency response.

A Clinician's Guide to Running Custom Machine-Learning Models in an Electronic Health Record Environment.

We recently brought an internally developed machine-learning model for predicting which patients in the emergency department would require hospital admission into the live electronic health record environment. Doing so involved navigating several engineering challenges that required the expertise of multiple parties across our institution. Our team of physician data scientists developed, validated, and implemented the model. We recognize a broad interest and need to adopt machine-learning models into clinical practice and seek to share our experience to enable other clinician-led initiatives. This Brief Report covers the entire model deployment process, starting once a team has trained and validated a model they wish to deploy in live clinical operations.

HIV care cascade and associated factors among men who have sex with men, transgender women, and genderqueer individuals in Zimbabwe: findings from a biobehavioural survey using respondent-driven sampling.

BACKGROUND: Globally, men who have sex with men (MSM), transgender women, and genderqueer individuals are at greater risk for HIV than the general population although little data are available from these groups in Zimbabwe, a country with a national adult HIV prevalence of 12·9%. We aimed to examine progress towards the UNAIDS 90-90-90 treatment targets and factors associated with meeting the targets among a sample of MSM, transgender women, and genderqueer individuals in Zimbabwe. METHODS: In this cross-sectional survey in 2019, we used respondent-driven sampling to identify MSM, transgender women, and genderqueer individuals aged at least 18 years to participate in a biobehavioural survey in Harare and Bulawayo, Zimbabwe. Participants were eligible to participate if they were assigned male at birth; had engaged in anal or oral sex with a man in the past 12 months; resided in Harare or Bulawayo for at least 1 month; spoke English, Shona, or Ndebele; provided written informed consent; and were in possession of a valid recruitment coupon if applicable. Enrolled participants completed a questionnaire and underwent HIV testing, and off-site viral load testing was done on all HIV-positive samples. Unweighted bivariate analyses and multivariable logistic regression models were used to evaluate the association of sociodemographic, behavioural, and other factors with HIV-positive status awareness among MSM, transgender women, and genderqueer individuals, and with viral load suppression among MSM. Analyses were done firstly using self-reported information and then by classifying those with a viral load of less than 200 copies per mL as being aware of their status and on treatment (viral load recategorisation). FINDINGS: Among MSM, 248 (21%; 95% CI 19-24) of 1176 tested positive for HIV. Of those who tested positive, based on self-report, 119 (48%; 95% CI 42-54) reported knowing their HIV status, of whom 112 (94%; 88-98) reported using antiretroviral therapy (ART), of whom 89 (79%; 71-87) had viral load suppression. Based on viral load recategorisation, 180 (73%; 67-78) of 248 MSM testing HIV positive reported knowing their HIV status, of whom 174 (97%; 93-99) reported using ART, of whom 151 (87%; 81-91) had viral load suppression. 92 (28%; 23-33) of 335 transgender women and genderqueer individuals tested positive for HIV. Based on self-reports from these individuals 34 (37%; 27-48) of 92 participants reported knowing their HIV status, of whom 31 (91%; 76-98) reported using ART, of whom 27 (87%; 70-96%) had viral load suppression. Based on viral load recategorisation of data from transgender women and genderqueer participants, 53 (58%; 47-58) of 92 reported awareness of their HIV status, of whom 50 (94%; 84-99) reported using ART, of whom 46 (92%; 81-98) had viral load suppression. HIV-positive MSM aged 18-24 years had lower odds of being aware of their status than those aged at least 35 years (adjusted odds ratio [aOR] 0·34; 95% CI 0·13-0·92), as did HIV-positive MSM aged 25-34 years (aOR 0·26; 0·12-0·56). HIV-positive MSM aged 18-24 years also had a lower odds of having viral load suppression than those aged 35 years and older (aOR 0·35; 0·16-0·78), as did those aged 25-34 years (aOR 0·36; 0·19-0·67). No factors were significantly associated with awareness among transgender women and genderqueer individuals in multivariable models. INTERPRETATION: Our survey showed that HIV prevalence was high and the largest difference between our results and the 90-90-90 treatment targets was in HIV status awareness, indicating the need for improvements in engaging MSM (especially young MSM), transgender women, and genderqueer individuals in HIV testing services. FUNDING: US President's Emergency Plan for AIDS Relief through the US Centers for Disease Control and Prevention.

MPrEP+ study protocol: a prospective cohort study assessing the feasibility and acceptability of an HIV pre-exposure prophylaxis (PrEP) strategy for male clients of female sex workers in Kisumu, Kenya.

INTRODUCTION: Male clients (MCs) are integral to sex work-driven HIV transmission dynamics as sexual partners of female sex worker (FSW). MCs contribute disproportionately to incident HIV globally and in sub-Saharan Africa, with 27% of new infections attributed to MCs of FSW and other partners of key populations. Gaps in coverage of HIV testing and prevention services for men, including MCs, are well-documented, yet research and innovative interventions to improve MC uptake of effective prevention services, including pre-exposure prophylaxis (PrEP), are scarce. METHODS AND ANALYSIS: MPrEP+ is a cohort study designed to assess the feasibility and acceptability of a PrEP-focused HIV prevention strategy providing daily oral tenofovir/emtricitabine (TDF/FTC) in combination with three adherence self-management interventions: (1) use of a validated point-of-care urine drug-level assay with real-time feedback and tailored self-management counselling; (2) frequent HIV self-testing; and (3) weekly one-way text messaging. This package of interventions is being delivered to 120 MCs enrolled in the study in Kisumu, Kenya over a 6-month period. The primary outcome is PrEP adherence at 6 months as measured by PrEP drug levels. Bivariate and multivariable regression models will be used to identify predictors of PrEP adherence. We will also explore associations of sociodemographic characteristics and PrEP beliefs with PrEP adherence. ETHICS AND DISSEMINATION: The study was approved by the Columbia University Irving Medical Center Institutional Review Board and the Maseno University Ethical Review Committee. Study enrolment was initiated in November 2021 with participant follow-up planned through August 2022. Study results will be submitted for publication in peer-reviewed journals. Summaries and infographics of study findings will be developed and distributed to MC, FSW and stakeholders working in HIV prevention and support for people who sell and buy sex, including Kenya's Ministry of Health. TRIAL REGISTRATION NUMBER: NCT04898699; Registered on 24 May 2021.