Assessment of the performance of the plasma separation card for HIV-1 viral load monitoring in South Africa.

Scaling up of newer innovations that address the limitations of the dried blood spot and the logistics of plasma monitoring is needed. We employed a multi-site, cross-sectional assessment of the plasma separation card (PSC) on blood specimens collected from all consenting adults, assenting young and pediatric patients living with HIV from 10 primary healthcare clinics in South Africa. Venous blood for EDTA-plasma samples was collected and analyzed according to the standard of care assay, while collected capillary blood for the PSC samples was analyzed using the Roche COBAS AmpliPrep/Cobas TaqMan (CAP/CTM) HIV-1 Test at the National Reference laboratories. McNemar tests assessed the differences in concordance between the centrifuged plasma and dried plasma spots. The usability of PSC by blood spotting, PSC preparation, and pre-analytical work was assessed by collecting seven-point Likert-scale data from healthcare and laboratory workers. We enrolled 538 patients, mostly adults [n = 515, 95.7% (95% CI: 93.7%-97.1%)] and females [n = 322, 64.2% (95% CI: 60.0%-68.1%)]. Overall, 536 paired samples were collected using both PSC- and EDTA-plasma diagnostics, and 502 paired PSC- and EDTA-plasma samples assessed. Concordance between the paired samples was obtained for 446 samples. Analysis of these 446 paired samples at 1,000 copies per milliliter threshold yielded an overall sensitivity of 87.5% [95% CI: 73.2%-95.8%] and specificity of 99.3% [95% CI: 97.9%-99.8%]. Laboratory staff reported technical difficulties in most tasks. The usability of the PSC by healthcare workers was favorable. For policymakers to consider PSC scale-up for viral load monitoring, technical challenges around using PSC at the clinic and laboratory level need to be addressed. IMPORTANCE: Findings from this manuscript emphasize the reliability of the plasma separation card (PSC), a novel diagnostic method that can be implemented in healthcare facilities in resource-constrained settings. The agreement of the PSC with the standard of care EDTA plasma for viral load monitoring is high. Since the findings showed that these tests were highly specific, we recommend a scale-up of PSC in South Africa for diagnosis of treatment failure.

How much does HIV self-testing cost in low and middle income countries? A systematic review of evidence from economic studies.

Objectives: HIV self-testing (HIVST) has been proposed as an innovative strategy to diagnose human immunodeficiency virus (HIV). While HIVST offers the potential to broaden accessibility of early HIV diagnosis and treatment initiation, this testing strategy incurs additional cost and requires confirmatory testing and treatment. We have conducted the first systematic review to summarize the current economic literature for HIVST in low- and middle-income countries (LMICs). Design: A search strategy was developed including key terms for HIV, self-testing and cost-effectiveness and was conducted in Medline and Embase databases. Studies were included that reported costs per outcome and included both cost-effectiveness and cost-utility outcome measures. The search strategy identified publications up until August 15, 2023 were included. Abstract and full text screening was conducted and a standardized data abstraction form was used for included studies. Costs are reported in USD, 2020. Results: Our search strategy identified 536 total titles from the search strategy, which were screened down to 25 relevant studies that provided both cost and outcome data on HIVST. There was significant heterogeneity in the HIVST intervention, study population, costs and outcomes reported among included studies. Cost per person tested ranged from $1.09-155. Cost per case diagnosed ranged from $20-1,277. Cost-utility estimates ranged from cost-saving to $1846 per DALY averted. Higher cost-effectiveness estimates were associated with more expensive testing algorithms with increased support for linkage to care and post-test counseling. Conclusion: All studies considered HIVST cost-effective although major drivers were identified included underlying HIV prevalence, testing cost and linkage to care. HIVST is likely to be cost-effective in a LMIC context, however policy makers should be aware of the drivers of cost-effectiveness when implementing HIVST programs as these underlying factors can impact the overall cost-effectiveness of HIVST.

Variation in HIV care and treatment outcomes by facility in South Africa, 2011-2015: A cohort study.

BACKGROUND: Despite widespread availability of HIV treatment, patient outcomes differ across facilities. We propose and evaluate an approach to measure quality of HIV care at health facilities in South Africa's national HIV program using routine laboratory data. METHODS AND FINDINGS: Data were extracted from South Africa's National Health Laboratory Service (NHLS) Corporate Data Warehouse. All CD4 counts, viral loads (VLs), and other laboratory tests used in HIV monitoring were linked, creating a validated patient identifier. We constructed longitudinal HIV care cascades for all patients in the national HIV program, excluding data from the Western Cape and very small facilities. We then estimated for each facility in each year (2011 to 2015) the following cascade measures identified a priori as reflecting quality of HIV care: median CD4 count among new patients; retention 12 months after presentation; 12-month retention among patients established in care; viral suppression; CD4 recovery; monitoring after an elevated VL. We used factor analysis to identify an underlying measure of quality of care, and we assessed the persistence of this quality measure over time. We then assessed spatiotemporal variation and facility and population predictors in a multivariable regression context. We analyzed data on 3,265 facilities with a median (IQR) annual size of 441 (189 to 988) lab-monitored HIV patients. Retention 12 months after presentation increased from 42% to 47% during the study period, and viral suppression increased from 66% to 79%, although there was substantial variability across facilities. We identified an underlying measure of quality of HIV care that correlated with all cascade measures except median CD4 count at presentation. Averaging across the 5 years of data, this quality score attained a reliability of 0.84. Quality was higher for clinics (versus hospitals), in rural (versus urban) areas, and for larger facilities. Quality was lower in high-poverty areas but was not independently associated with percent Black. Quality increased by 0.49 (95% CI 0.46 to 0.53) standard deviations from 2011 to 2015, and there was evidence of geospatial autocorrelation (p < 0.001). The study's limitations include an inability to fully adjust for underlying patient risk, reliance on laboratory data which do not capture all relevant domains of quality, potential for errors in record linkage, and the omission of Western Cape. CONCLUSIONS: We observed persistent differences in HIV care and treatment outcomes across South African facilities. Targeting low-performing facilities for additional support could reduce overall burden of disease.

Cost and Impact of Dried Blood Spot Versus Plasma Separation Card for Scale-up of Viral Load Testing in Resource-limited Settings.

BACKGROUND: Routine plasma viral load (VL) testing is recommended for monitoring human immunodeficiency virus-infected patients on antiretroviral therapy. In Zambia, VL scale-up is limited due to logistical obstacles around plasma specimen collection, storage, and transport to centralized laboratories. Dried blood spots (DBSs) could circumvent many logistical challenges at the cost of increased misclassification. Recently, plasma separation cards (PSCs) have become available and, though more expensive, have lower total misclassification than DBSs. METHODS: Using a geospatial model created for optimizing VL utilization in Zambia, we estimated the short-term cost of uptake/correct VL result using either DBSs or PSCs to increase VL access on equipment available in-country. Five scenarios were modeled: (1) plasma only (status quo); (2) plasma at high-volume sites, DBS at low-volume sites; (3) plasma at high-volume sites, PSC at low-volume sites; (4) PSC only; (5) DBS only. RESULTS: Scenario 1 resulted in 795 342 correct results due to limited patient access. When allowing for full and partial adoption of dried specimens, access increases by 19%, with scenario 3 producing the greatest number of correct results expected (929 857). The average cost per correct VL result was lowest in the plasma + DBS scenario at $30.90 compared to $31.62 in our plasma + PSC scenario. The cost per correct result of using dried specimens only was dominated in the incremental analysis, due primarily to fewer correct results. CONCLUSIONS: Adopting the partial use of dried specimens will help achieve improved VL access for patients at the lowest cost per correct result.

Persistent High Burden of Advanced HIV Disease Among Patients Seeking Care in South Africa's National HIV Program: Data From a Nationwide Laboratory Cohort.

Background: The South African national HIV program has increased antiretroviral therapy (ART) coverage over the last decade, supported by policy changes allowing for earlier ART initiation. However, many patients still enter care with advanced (<200 cells/µL) and very advanced (<100 cells/µL) HIV disease. We assessed disease progression at entry to care using nationwide laboratory data. Methods: We constructed a national HIV cohort using laboratory records containing HIV RNA loads and CD4 counts from 2004 to 2016 to determine entry into care. We estimated numbers and proportions of adults with the first CD4 count <100 cells/ µL or 100-199 cells/µL. We calculated relative risks of presenting with advanced disease associated with male sex. Results: 8.04 million first CD4 results were identified. From 2005 to 2011, the proportion of patients entering into care with CD4 count <200 cells/µL declined from 46.8% to 35.6%. From 2011 onward, the proportion of patients entering ART with advanced HIV disease has remained relatively unchanged. In 2016, we estimated that of 654 868 patients entering care, 32.9% had advanced HIV disease, and 16.8% had very advanced HIV disease. Men were almost twice as likely as women (23.1% vs 12.6% ) to enter care with very advanced HIV disease. Conclusions: The proportion of patients presenting with advanced HIV disease in South Africa remains consistently high despite ART scale-up, representing a large and avoidable burden of morbidity. Early HIV diagnosis, rapid linkage to ART and approaches to attract men into early ART initiation should be prioritized.

Scale-up of Early Infant HIV Diagnosis and Improving Access to Pediatric HIV Care in Global Plan Countries: Past and Future Perspectives.

Investment to scale-up early infant diagnosis (EID) of HIV has increased substantially in the last decade. This investment includes physical infrastructure, equipment, human resources, and specimen transportation systems as well as specialized mechanisms to deliver laboratory results to clinics. The Global Plan Towards the Elimination of New HIV Infections Among Children by 2015 and Keeping Their Mothers Alive, as well as related international initiatives to prevent mother-to-child transmission of HIV and treat children living with HIV have been important drivers of this scale-up by mobilizing resources, creating advocacy, developing normative recommendations, and providing direct technical support to countries through the global community of international stakeholders. As a result, the number of early infant diagnosis tests performed annually has increased 10-fold between 2005 and 2015, and many thousands of infants are now receiving life-saving antiretroviral therapy because of this improved access. Despite these efforts and many success stories, timely infant diagnosis remains a challenge in many Global Plan countries. The most recent data (from the end of 2015) suggest a large variation in access. Some countries report that almost 90% of HIV-exposed infants are being tested; others report that the level of access has stagnated at 30%. Still, just over half of all exposed infants in Global Plan countries receive a test in the first 2 months of life. We discuss the key factors that are responsible for this scale-up of diagnostic capacity, highlight some of the challenges that have hampered progress, and describe priorities for the future that can help maintain momentum to achieve true universal access to HIV testing for children.

Design and implementation of an external quality assessment program for HIV viral load measurements using dried blood spots.

An external quality assurance program was developed for HIV-1 RNA viral load measurements taken from dried blood spots using a reference panel and field-collected specimens. The program demonstrated that accurate and reproducible quantitation can be obtained from field-collected specimens. Residual proviral DNA may confound interpretation in virologically suppressed subjects.

[A proposal of new indices for hospital management]. / Propuesta de índices de gestión de servicios médico-quirúrgicos hospitalarios mediante técnicas estadísticas multivariantes.

BACKGROUND: Diagnosis related groups (DRGs) are the most reliable patient classification system in hospital management. When this information is unavailable, other reliable classification system must be used. AIM: To obtain useful indices for hospital management, based on descriptive multivariate techniques. MATERIAL AND METHODS: Data on admissions to a University Hospital during 2003 were analyzed. Number of discharges, lethality rate, re-admission rate, number of outpatient consultations, length of hospital stay and surgical complexity index were analyzed, using information obtained by the Operations Management Department. The Principal Components Analysis (PCA) technique was applied and the R correlation matrix was used. RESULTS: A total of 24,345 discharges were analyzed. The first two principal components were selected, accounting cumulatively for 76% of data variability (47% for the first and 29% for the second). CONCLUSIONS: The first component may be assimilated to a new index representing the difficulty of the attended cases, which we have termed Case Complexity. The second principal component would explain the number of attended persons, which we have termed Case Load. These two indices allow us to classify hospital services.

Propuesta de índices de gestión de servicios médico-quirúrgicos hospitalarios mediante técnicas estadísticas multivariantes / A proposal of new indices for hospital management

Background: Diagnosis related groups (DRGs) are the most reliable patient classification system in hospital management. When this information is unavailable, other reliable classification system must be used. Aim: To obtain useful indices for hospital management, based on descriptive multivariate techniques. Material and Methods: Data on admissions to a University Hospital during 2003 were analyzed. Number of discharges, lethality rate, re-admission rate, number of outpatient consultations, length of hospital stay and surgical complexity index were analyzed, using information obtained by the Operations Management Department. The Principal Components Analysis (PCA) technique was applied and the R correlation matrix was used. Results: A total of 24,345 discharges were analyzed. The first two principal components were selected, accounting cumulatively for 76percent of data variability (47percent for the first and 29percent for the second). Conclusions: The first component may be assimilated to a new index representing the difficulty of the attended cases, which we have termed Case Complexity. The second principal component would explain the number of attended persons, which we have termed Case Load. These two indices allow us to classify hospital services.

[Indices of public health services and resource allocation from the Health Ministry of Chile]. / Indicadores de gestión de servicios de salud públicos y asignación de recursos desde el Ministerio de Salud de Chile.

BACKGROUND: Chile has a National Health Services System, formed by 29 Health Services. An efficient resource distribution among this services is crucial for an efficient health care delivery. AIM: To obtain indices from the Chilean Public Health Services, that could improve allocation of resources. MATERIAL AND METHODS: Information from the Chilean Public Health Services, corresponding to activities during 2001 budgetary period, was collected. This is the latest complete and official information for the totality of Health Services in the country. Seventeen variables generated or monitored by the Instituto Nacional de Estadísticas (INE), the Ministerio de Salud (MINSAL), the Ministerio de Hacienda, the Ministerio de Planificación y Cooperación (MIDEPLAN) and the Fondo Nacional de Salud (FONASA) were studied. The Main Components Analysis (ACP) was used, obtained from the R correlation matrix. RESULTS: The first two main components were selected, with an accumulated percentage of explained variability of 63.05%. The first component is related to the population assigned to each Health Service. This corresponds to the number of people needed to treat in the hospitals of these Services and their answer to this demand, justified by the expenses in which each Health Service incurs. There is an inverse relation of the first component with health indicators, measured by burden of disease and death. The second main component would represent the social and economic characteristics of the population, poor and very poor populations and public health insurance beneficiaries, to take care of in each Health Service. CONCLUSIONS: Health indicators in each Health Service are not considered a priority for resource distribution among Health Services in the country. The transference is done considering the indices contained in the two main components defined.