Evaluation of GeneXpert and advanced biological laboratories UltraGene HCV diagnostic detection and performance against Roche real time PCR in Myanmar.

BACKGROUND: Developing countries experience limited access to HCV laboratory tests for different reasons. Providing near to real-time HCV testing and results especially to at-risk populations including those in rural settings for timely initiation to treatment is key. Within a rural Myanmar setting, we compared HCV diagnostic detection and quantification of the GeneXpert, and Advanced Biological Laboratories UltraGene-HCV assays against the gold standard and reference method Roche real-time HCV in Myanmar. METHODS: Blood samples from 158 high-risk individuals were assessed using three different methods at baseline. Results were checked for normality and log transformed. Log differences and bias between methods were calculated and correlated. Pearson's correlation coefficient was used to determine the association of HCV viral loads across all methods. The level of agreement with the standard method (Roche real time HCV) was assessed using Bland-Altman analyses. RESULTS: There was a strong positive correlation coefficient between all three methods with GeneXpert and Roche having the strongest, r = 0.96, (p<0.001). Compared to Roche, ABL (mean difference, 95 % limits of agreement; -0.063 and -1.4 to 1.3 Log10IU/mL) and GeneXpert (mean difference, 95 % limits of agreement; -0.28 and -0.7 to 1.8 Log10IU/mL) showed a good level of agreement with the GeneXpert being slightly superior. CONCLUSION: We demonstrate the excellent performance and no-inferiority, in terms of levels of agreements of both GeneXpert and ABL compared to the Roche platform and supporting the use of the POC assays as alternative a cost-effective methods in HCV detection and diagnosis in developing and low resource settings countries.

Person-centred, integrated non-communicable disease and HIV decentralized drug distribution in Eswatini and South Africa: outcomes and challenges.

INTRODUCTION: Non-communicable diseases (NCDs) are highly prevalent in people living with HIV above 50 years of age and account for increasing mortality. There is little published evidence supporting person-centred, integrated models of HIV care, hypertension and diabetes treatment in southern Africa, and no data demonstrating mortality reduction. Where clinical visits for NCDs and HIV cannot be combined, integrated medication delivery presents an opportunity to streamline care and reduce patient costs. We present experiences of integrated HIV and NCD medication delivery in Eswatini and South Africa, focusing on programme successes and implementation challenges. Programmatic data from Eswatini's Community Health Commodities Distribution (CHCD) from April 2020 to December 2021 and South Africa's Central Chronic Medicines Dispensing and Distribution (CCMDD) from January 2016 to December 2021 were provided by programme managers and are summarized here. DISCUSSION: Launched in 2020, Eswatini's CHCD provides over 28,000 people with and without HIV with integrated services, including HIV testing, CD4 cell count testing, antiretroviral therapy refills, viral load monitoring and pre-exposure prophylaxis alongside NCD services, including blood pressure and glucose monitoring and hypertension and diabetes medication refills.  Communities designate neighbourhood care points and central gathering places for person-centred medication dispensing.  This programme reported fewer missed medication refill appointments among clients in community settings compared to facility-based settings. South Africa's CCMDD utilizes decentralized drug distribution to provide medications for over 2.9 million people, including those living with HIV, hypertension and diabetes.  CCMDD incorporates community-based pickup points, facility "fast lanes" and adherence clubs with public sector health facilities and private sector medication collection units.  There are no out-of-pocket payments for medications or testing commodities.  Wait-times for medication refills are lower at CCMDD sites than facility-based sites.  Innovations to reduce stigma include uniformly labelled medication packages for NCD and HIV medications. CONCLUSIONS: Eswatini and South Africa demonstrate person-centred models for HIV and NCD integration through decentralized drug distribution. This approach adapts medication delivery to serve individual needs and decongest centralized health facilities while efficiently delivering NCD care.  To bolster programme uptake, additional reporting of integrated decentralized drug distribution models should include HIV and NCD outcomes and mortality trends.

Clients in Uganda accessing preferred differentiated antiretroviral therapy models achieve higher viral suppression and are less likely to miss appointments: a cross-sectional analysis.

INTRODUCTION: The Uganda Ministry of Health recommends facility- and community-based differentiated antiretroviral therapy (DART) models to support person-centred care for eligible clients receiving antiretroviral therapy (ART). Healthcare workers assess client eligibility for one of six DART models upon initial enrolment; however, client circumstances evolve, and their preferences are not routinely adjusted. We developed a tool to understand the proportion of clients accessing preferred DART models and compared the outcomes of clients accessing preferred DART models to the outcomes of clients not receiving preferred DART models. METHODS: We conducted a cross-sectional study. A sample of 6376 clients was selected from 113 referrals, general hospitals and health centres purposely selected from 74 districts. Clients receiving ART accessing care from the sampled sites were eligible for inclusion. Healthcare workers interviewed clients (caretakers of clients under 18), over a 2-week period between January and February 2022 using a client preference tool to elicit whether clients were receiving DART services through their preferred model. Treatment outcomes of viral load test, viral load suppression and missed appointment date were extracted from clients' medical files before or immediately after the interview and de-identified. The descriptive analysis determined the interaction between client preferences and predefined treatment outcomes by comparing outcomes of clients whose care aligned with their preferences to outcomes of clients whose care misaligned with their preferences. RESULTS: Of 25% (1573/6376) of clients not accessing their preferred DART model, 56% were on facility-based individual management and 35% preferred fast-track drug refills model. Viral load coverage was 87% for clients accessing preferred DART models compared to 68% among clients not accessing their preferred model. Viral load suppression was higher among clients who accessed the preferred DART model (85%) compared to (68%) clients who did not access their preferred DART model. Missed appointments were lower at 29% for clients who accessed preferred DART models compared to 40% among clients not enrolled in the DART model of their choice. CONCLUSIONS: Clients who accessed their preferred DART model have better clinical outcomes. Preferences should be integrated throughout health systems, improvement interventions, policies and research efforts to ensure client-centred care and client autonomy.

Integrating global HIV services with primary health care: a key step in sustainable HIV epidemic control.

Ending the HIV epidemic relies in part on integrating stand-alone HIV programming with primary health-care platforms to improve population-level health and ensure sustainability. Integration of HIV and primary health care services in sub-Saharan Africa improves both outcomes. Existing models support both integrating primary health care services into existing HIV services, and incorporating HIV services into primary health care platforms, with optimal programming based on local contexts and local epidemic factors. Person-centred differentiated service delivery, community-based interventions, and a well supported health workforce form the backbone of successful integration. Strategic financing to optimise HIV and primary health care integration requires well-coordinated partnerships with host governments, private sector companies, multilateral stakeholders, development banks, and non-government organisations. Programme success will require increased flexibility of international donors' implementation guidance as well as involvement of local communities and civil society organisations. As we seek to end the HIV epidemic by 2030 amidst a constrained global economic climate, integration of HIV programming with primary health care offers an avenue of opportunity and hope.

Treatment outcomes and costs of a simplified antiretroviral treatment strategy for hepatitis C among Hepatitis C Virus and Human Immuno deficiency Virus co-infected patients in Ukraine.

Background and Aim: To demonstrate the use of a standard dose of ledipasvir (LDV) and sofosbuvir (SOF), with or without ribavirin, to treat hepatitis C and hepatitis C/HIV co-infection in Ukraine. Methods: Eligible HCV viraemic adults from two clinics in Kyiv were treated with LDV/SOF with or without weight-based ribavirin for 12 weeks. Clinical assessments were performed at screening and at week 24, and as needed; treatment was dispensed every 4 weeks. The primary outcome was sustained virologic response (SVR) 12 weeks after treatment, with analysis by intention to treat. Cost per patient was estimated in USD (2018) over the 24-week period. Results: Of 868 patients included in the study and initiated on therapy, 482 (55.5%) were co-infected with HIV. The common genotypes were 1 (74.1%) and 3 (22%). Overall, SVR was achieved in 831 of the 868 patients (95.7%). SVR in patients with hepatitis C alone and hepatitis C/HIV co-infection was 98.4% and 93.6%, respectively. Adverse events were infrequent and usually mild. Using generic medication, cost per patient was estimated at US$680. Conclusion: A standard dose of LDV and SOF, with ribavirin as per protocol, resulted in good outcomes for patients with both hepatitis C alone and co-infected with hepatitis C/HIV. Program costs in Ukraine were modest using generic medication.

Treatment outcomes and costs of a simplified antiviral treatment strategy for hepatitis C among monoinfected and HIV and/or hepatitis B virus-co-infected patients in Myanmar.

Access to hepatitis C virus (HCV) testing and treatment is limited in Myanmar. We assessed an integrated HIV and viral hepatitis testing and HCV treatment strategy. Sofosbuvir/velpatasvir (SOF/VEL) ± weight-based ribavirin for 12 weeks was provided at three treatment sites in Myanmar and sustained virologic response (SVR) assessed at 12 weeks after treatment. Participants co-infected with HBV were treated concurrently with tenofovir. Cost estimates in 2018 USD were made at Yangon and Mandalay using standard micro-costing methods. 803 participants initiated SOF/VEL; 4.8% were lost to follow-up. SVR was achieved in 680/803 (84.6%) by intention-to-treat analysis. SVR amongst people who inject drugs (PWID) was 79.7% (381/497), but 92.5% among PWID on opioid substitution therapy (OST) (74/80), and 97.4% among non-PWID (298/306). Utilizing data from 492 participants, of whom 93% achieved SVR, the estimated average cost of treatment per patient initiated was $1030 (of which 54% were medication costs), with a production cost per successful outcome (SVR) of $1109 and real-world estimate of $1250. High SVR rates were achieved for non-PWID and PWID on OST. However, the estimated average cost of the intervention (under the assumption of no genotype testing and reduced real-world effectiveness) of $1250/patient is unaffordable for a national elimination strategy. Reductions in the cost of antivirals and linkage to social and behavioural health services including substance use disorder treatment to increase retention and adherence to treatment are critical to HCV elimination in this population.

PEPFAR's response to the convergence of the HIV and COVID-19 pandemics in Sub-Saharan Africa.

INTRODUCTION: The COVID-19 pandemic reached the African continent in less than three months from when the first cases were reported from mainland China. As COVID-19 preparedness and response plans were rapidly instituted across sub-Saharan Africa, many governments and donor organizations braced themselves for the unknown impact the COVID-19 pandemic would have in under-resourced settings with high burdens of PLHIV. The potential negative impact of COVID-19 in these countries is uncertain, but is estimated to contribute both directly and indirectly to the morbidity and mortality of PLHIV, requiring countries to leverage existing HIV care systems to propel COVID-19 responses, while safeguarding PLHIV and HIV programme gains. In anticipation of COVID-19-related disruptions, PEPFAR promptly established guidance to rapidly adapt HIV programmes to maintain essential HIV services while protecting recipients of care and staff from COVID-19. This commentary reviews PEPFAR's COVID-19 technical guidance and provides country-specific examples of programme adaptions in sub-Saharan Africa. DISCUSSION: The COVID-19 pandemic may pose significant risks to the continuity of HIV services, especially in countries with high HIV prevalence and weak and over-burdened health systems. Although there is currently limited understanding of how COVID-19 affects PLHIV, it is imperative that public health systems and academic centres monitor the impact of COVID-19 on PLHIV. The general principles of the HIV programme adaptation guidance from PEPFAR prioritize protecting the gains in the HIV response while minimizing in-person home and facility visits and other direct contact when COVID-19 control measures are in effect. PEPFAR-supported clinical, laboratory, supply chain, community and data reporting systems can play an important role in mitigating the impact of COVID-19 in sub-Saharan Africa. CONCLUSIONS: As community transmission of COVID-19 continues and the number of country cases rise, fragile health systems may be strained. Utilizing the adaptive, data-driven programme approaches in facilities and communities established and supported by PEPFAR provides the opportunity to strengthen the COVID-19 response while protecting the immense gains spanning HIV prevention, testing and treatment reached thus far.

Twelve-Month Outcomes of Community-Based Differentiated Models of Multimonth Dispensing of ART Among Stable HIV-Infected Adults in Lesotho: A Cluster-Randomized Noninferiority Trial.

BACKGROUND: Lesotho adopted the test-and-treat approach for HIV treatment in June 2016, which increased antiretroviral treatment (ART) clinic volume. We evaluated community-based vs. facility-based differentiated models of multimonth dispensing of ART among stable HIV-infected adults in Lesotho. METHODS: Thirty facilities were randomized to 3 arms, facility 3-monthly ART (3MF) (control), community ART groups (3MC), and 6-monthly community distribution points (6MCD). We estimated risk differences (RDs) between arms using population-averaged generalized estimating equations, controlling for baseline imbalances and specifying for clustering. The primary outcome was retention in ART care by intention-to-treat and virologic suppression as a secondary outcome (ClinicalTrials.gov: NCT03438370). RESULTS: A total of 5,336 participants were enrolled, with 1898, 1558, and 1880 in 3MF, 3MC, and 6MCD, respectively. Retention in ART care was not different across arms and achieved the prespecified noninferiority limit (-3.25%) between 3MC vs. 3MF (control); 6MCD vs. 3MF; and 6MCD vs. 3MC, adjusted RD = -0.1% [95% confidence interval (CI): -1.6% to 1.5%], adjusted RD = -1.3% (95% CI: -3.0% to 0.5%), and adjusted RD = -1.2% (95% CI: -2.9% to 0.5%), respectively. After 12 months, 98.6% (n = 1503), 98.1% (n = 1126), and 98.3% (n = 1285) were virally load (VL) suppressed in 3MF, 3MC, and 6MCD, respectively. There were no differences in VL between 3MC vs. control and 6MCD vs. control, risk ratio (RR) = 1.00 (95% CI: 0.98 to 1.01) and RR = 1.00 (95% CI: 0.98 to 1.01), respectively. CONCLUSIONS: There were no differences in retention and VL suppression for stable HIV-infected participants receiving multimonth dispensing of ART within community-based differentiated models when compared with the facility-based standard-of-care model.

The Critical Role of Supply Chains in Preventing Human Immunodeficiency Virus Drug Resistance in Low- and Middle-Income Settings.

The functioning of the supply chain may be a driving factor behind the development of human immunodeficiency virus (HIV) drug resistance (HIVDR) in many low- and middle-income countries (LMICs). Additionally, the effectiveness of supply chains will likely impact the scale-up of both viral-load monitoring and HIVDR testing. This article describes the complexities of global supply chains relevant for LMICs and presents early data on stock-outs and drug substitutions in several countries supported by the US President's Emergency Plan for AIDS Relief. Supply chain systems will need to be strengthened to minimize interruptions as new antiretroviral therapy regimens are introduced and to facilitate adoption of new laboratory technologies.

Non-communicable diseases and HIV care and treatment: models of integrated service delivery.

OBJECTIVES: Non-communicable diseases (NCD) are a growing cause of morbidity in low-income countries including in people living with human immunodeficiency virus (HIV). Integration of NCD and HIV services can build upon experience with chronic care models from HIV programmes. We describe models of NCD and HIV integration, challenges and lessons learned. METHODS: A literature review of published articles on integrated NCD and HIV programs in low-income countries and key informant interviews were conducted with leaders of identified integrated NCD and HIV programs. Information was synthesised to identify models of NCD and HIV service delivery integration. RESULTS: Three models of integration were identified as follows: NCD services integrated into centres originally providing HIV care; HIV care integrated into primary health care (PHC) already offering NCD services; and simultaneous introduction of integrated HIV and NCD services. Major challenges identified included NCD supply chain, human resources, referral systems, patient education, stigma, patient records and monitoring and evaluation. The range of HIV and NCD services varied widely within and across models. CONCLUSIONS: Regardless of model of integration, leveraging experience from HIV care models and adapting existing systems and tools is a feasible method to provide efficient care and treatment for the growing numbers of patients with NCDs. Operational research should be conducted to further study how successful models of HIV and NCD integration can be expanded in scope and scaled-up by managers and policymakers seeking to address all the chronic care needs of their patients.

Assessing the costs and effects of antiretroviral therapy task shifting from physicians to other health professionals in ethiopia.

OBJECTIVE: To evaluate the effects, costs, and cost-effectiveness of different degrees of antiretroviral therapy task shifting from physician to other health professionals in Ethiopia. DESIGN: Two-year retrospective cohort analysis on antiretroviral therapy patients coupled with cost analysis. INTERVENTIONS: Facilities with minimal or moderate task shifting compared with facilities with maximal task shifting. Maximal task shifting is defined as nonphysician clinicians handling both severe drug reactions and antiretroviral drug regimen changes. Secondary analysis compares health centers to hospitals. MAIN OUTCOME MEASURES: The primary effectiveness measure is the probability of a patient remaining actively on antiretroviral therapy for 2 years; the cost measure is the cost per patient per year. RESULTS: All facilities had some task shifting. About 89% of patients were actively on treatment 2 years after antiretroviral treatment (ART) initiation, with no statistically significant differences between facilities with maximal and minimal or moderate task shifting. It cost about $206 per patient per year for ART, with no statistically significant difference between the comparison groups. The cost-effectiveness of maximal task shifting is similar to minimal or moderate task shifting, with the same results obtained using regression to control for facility characteristics. CONCLUSIONS: Shifting the handling of both severe drug reactions and antiretroviral drug regimen changes from physicians to other clinical officers is not associated with a significant change in the 2-year treatment success rate or the costs of ART care. As an observational study, these results are tentative, and more research is needed in determining the optimal patterns of task shifting.

Implementation of a standardized HIV patient monitoring system in Guyana.

OBJECTIVE: To describe the process used to implement a comprehensive, standardized, and reliable national system for data collection for HIV care and treatment in Guyana; to provide examples of the program-level data resulting from implementation; and to highlight the monitoring benefits for national programs. METHODS: In 2007, Guyana's Ministry of Health and other key stakeholders adapted the World Health Organization's generic HIV care and antiretroviral therapy (ART) patient monitoring guidelines to fit the Guyana context, which included modifying the patient chart, patient registers, and cross-sectional and cohort reports. Following initial training and feedback from clinical staff, a national patient monitoring system (PMS) was finalized, piloted, and implemented at all care and treatment sites. Thereafter, sites received monthly supportive supervisory visits to review data collection and validate reports. RESULTS: Implementation of the PMS enabled analysis of cohort data for patients on ART. After 12 months, 79% of a combined national cohort of all 50 patients who started ART in June 2007 were alive and on first-line ART regimens. After six years, 58% of the first (April 2002) cohort of ART patients in the country were alive and on ART, with only two (8%) patients on second-line regimens. CONCLUSIONS: Implementation of a national PMS for standardized data collection and reporting across multiple clinical sites ultimately provided important and reliable information on utilization of services, patient outcomes, and survival rates on treatment. These data are used at the national level to monitor the efficacy of the HIV care and treatment program. Successful implementation requires early inclusion of all committed stakeholders and a dedicated human resource team to ensure sustainability of the system.

Implementation of a standardized HIV patient monitoring system in Guyana / Establecimiento de un sistema estandarizado de vigilancia de los pacientes infectados por el VIH en Guyana

OBJECTIVE: To describe the process used to implement a comprehensive, standardized, and reliable national system for data collection for HIV care and treatment in Guyana; to provide examples of the program-level data resulting from implementation; and to highlight the monitoring benefits for national programs. METHODS: In 2007, Guyana's Ministry of Health and other key stakeholders adapted the World Health Organization's generic HIV care and antiretroviral therapy (ART) patient monitoring guidelines to fit the Guyana context, which included modifying the patient chart, patient registers, and cross-sectional and cohort reports. Following initial training and feedback from clinical staff, a national patient monitoring system (PMS) was finalized, piloted, and implemented at all care and treatment sites. Thereafter, sites received monthly supportive supervisory visits to review data collection and validate reports. RESULTS: Implementation of the PMS enabled analysis of cohort data for patients on ART. After 12 months, 79 percent of a combined national cohort of all 50 patients who started ART in June 2007 were alive and on first-line ART regimens. After six years, 58 percent of the first (April 2002) cohort of ART patients in the country were alive and on ART, with only two (8 percent) patients on second-line regimens. CONCLUSIONS: Implementation of a national PMS for standardized data collection and reporting across multiple clinical sites ultimately provided important and reliable information on utilization of services, patient outcomes, and survival rates on treatment. These data are used at the national level to monitor the efficacy of the HIV care and treatment program. Successful implementation requires early inclusion of all committed stakeholders and a dedicated human resource team to ensure sustainability of the system.

OBJETIVO: Describir el proceso utilizado con el objeto de poner en práctica un sistema nacional integral, estandarizado y confiable de recopilación de datos sobre la atención y el tratamiento de la infección por el VIH en Guyana; suministrar ejemplos de los datos que se obtuvieron mediante el programa durante la ejecución; y subrayar las ventajas de la vigilancia para los programas nacionales. MÉTODOS: En el 2007, el Ministerio de Salud de Guyana y otros actores claves adaptaron al contexto de Guyana las directrices básicas de la Organización Mundial de la Salud sobre el seguimiento de los pacientes con VIH que reciben atención y tratamiento antirretrovírico; la adaptación implicó modificaciones en el expediente clínico, el registro de los pacientes, los informes transversales y los informes de cohortes. Después de una capacitación inicial y la retroalimentación por parte del personal médico, se finalizó un sistema nacional de seguimiento de los pacientes, que se puso a prueba y se puso en marcha en todos los centros de atención y tratamiento. Posteriormente, se realizaron visitas mensuales de supervisión y apoyo a los centros, con el fin de examinar la recopilación de los datos y validar los informes. RESULTADOS: La ejecución del programa de vigilancia de los pacientes permitió el análisis de los datos de las cohortes de pacientes en tratamiento antirretrovírico. Después de 12 meses, se encontró que 79 por ciento de una cohorte nacional combinada de los 50 pacientes que comenzaron tratamiento antirretrovírico en junio del 2007 estaban vivos y recibían tratamiento con antirretrovíricos de primera línea. Después de seis años, 58 por ciento de la primera cohorte de pacientes tratados con antirretrovíricos en el país (abril del 2002) estaban vivos, continuaban el tratamiento y solo dos pacientes (8 por ciento) recibían medicamentos de segunda línea. CONCLUSIONES: La ejecución de un programa nacional de supervisión de los pacientes con recopilación y notificación estandarizada de los datos en múltiples centros clínicos suministró en último término información importante y confiable sobre la utilización de los servicios, el desenlace clínico de los pacientes y las tasas de supervivencia con el tratamiento. Estos datos se usan a escala nacional con el fin de vigilar la eficacia del programa de atención y tratamiento de la infección por el VIH. La ejecución eficaz del programa exige la participación temprana de todos los actores claves comprometidos y un equipo de recursos humanos dedicado a velar por la sostenibilidad del sistema.

Racial differences in discrimination experiences and responses among minority substance users.

OBJECTIVES: Discrimination is associated with both mental and physical health, and may be a particularly important determinant of health among marginalized groups. This study assessed differences in discrimination experiences and responses to discrimination between Black and Latino active substance users in New York City. METHODS: 500 Black and 419 Latino active substance users were recruited through outreach workers, service agencies, and word of mouth. We collected data about different types of discrimination experienced (eg, discrimination due to race, gender, substance use), the domains in which it occurred (eg, at work, with police), and participants' responses to unfair treatment. RESULTS: Discrimination due to drug use was the most commonly reported type of discrimination among both Blacks and Latinos. Black respondents were more likely than Latinos to report discrimination due to their drug use (79% to 70%), race (39% to 23%), poverty (38% to 26%), gender (18% to 9%), and sexual orientation (38% to 6%). However, among those reporting discrimination due to drug use, Latinos experienced more rejection from family (81% to 70%), friends (73% to 60%), police (86% to 79%), employers (72% to 56%), and medical care professionals (29% to 18%). Black respondents were more likely to respond actively to discrimination, whereas Latino respondents were more likely to internalize experiences. CONCLUSIONS: Substantial differences exist in discrimination experiences and responses to discrimination between Black and Latino substance users. These differences may help explain racial and ethnic differences in health among marginalized populations, and identify avenues for effective, targeted intervention.