In this prospective, real-world cohort study nested within a national screening program for tuberculosis, Lesley Scott and colleagues compare the performance of Xpert MTB/RIF on a single sputum sample with different TB sputum detection technologies.

Improved access to anti-retroviral therapy increases the need for affordable monitoring using assays such as CD4 and/or viral load in resource-limited settings. Barriers to accessing treatment, high rates of loss to initiation and poor retention in care are prompting the need to find alternatives to conventional centralized laboratory testing in certain countries. Strong advocacy has led to a rapidly expanding repertoire of point-of-care tests for HIV. point-of-care testing is not without its challenges: poor regulatory control, lack of guidelines, absence of quality monitoring and lack of industry standards for connectivity, to name a few. The management of HIV increasingly requires a multidisciplinary testing approach involving hematology, chemistry, and tests associated with the management of non-communicable diseases, thus added expertise is needed. This is further complicated by additional human resource requirements and the need for continuous training, a sustainable supply chain, and reimbursement strategies. It is clear that to ensure appropriate national implementation either in a tiered laboratory model or a total decentralized model, clear country-specific assessments need to be conducted.

BackgroundExpansion of HIV viral load (VL) testing services are required to meet increased targets for monitoring patients on antiretroviral treatment. South Africa currently tests >4million VLs per annum in 16 highly centralised, automated high-throughput laboratories. The Xpert HIV-1 VL assay (Cepheid) was evaluated against in-country predicates, the Roche Cobas Taqmanv2 and Abbott HIV-1RT, to investigate options for expanding VL testing using GeneXpert’s random access, polyvalent capabilities and already established footprint in South Africa with the Xpert MTB/RIF assay (207 sites). Additionally, the performance of Xpert HIV-1VL on alternative, off-label specimen types, Dried Blood Spots (DBS) and whole blood, was investigated.MethodPrecision, accuracy (agreement) and clinical misclassification (1000cp/ml) of Xpert HIV-1VL plasma was compared to Taqmanv2 (n = 155) and Abbott HIV-1 RT (n = 145). Misclassification of Xpert HIV-1VL was further tested on DBS (n = 145) and whole blood (n = 147).ResultsXpert HIV-1VL demonstrated 100% concordance with predicate platforms on a standardised frozen, plasma panel (n = 42) and low overall percentage similarity CV of 1.5% and 0.9% compared to Taqmanv2 and Abbott HIV-1 RT, respectively. On paired plasma clinical specimens, Xpert HIV-1VL had low bias (SD 0.32–0.37logcp/ml) and 3% misclassification at the 1000cp/ml threshold compared to Taqmanv2 (fresh) and Abbott HIV-1 RT (frozen), respectively. Xpert HIV-1VL on whole blood and DBS increased misclassification (upward) by up to 14% with increased invalid rate. All specimen testing was easy to perform and compatible with concurrent Xpert MTB/RIF Tuberculosis testing on the same instrument.ConclusionThe Xpert HIV-1VL on plasma can be used interchangeably with existing predicate platforms in South Africa. Whole blood and DBS testing requires further investigation, but polyvalency of the GeneXpert offers a solution to extending VL testing services.

Implementation of Xpert MTB/RIF requires quality assessment. A pilot program using dried culture spots (DCSs) of inactivated Mycobacterium tuberculosis is described. Of 274 DCS results received, 2.19% generated errors; the remainder yielded 100% correct Mycobacterium tuberculosis detection. The probe A cycle threshold (C T ) variability of three DCS batches was <3.47. The study of longer-term DCS stability is ongoing.The Xpert MTB/RIF assay (Cepheid, Sunnyvale, CA) (1, 3-5, 9, 12, 13, 15, 19, 25) for the diagnosis of Mycobacterium tuberculosis has recently been endorsed by the WHO (28), and recommendations for data collection to quantify the impact of this GeneXpert (GX) technology are provided (26). Guidance, however, with respect to appropriate external quality assessment (EQA) programs is lacking (17). Current international tuberculosis (TB) EQA programs focus on microscopy, culture, and susceptibility testing laboratories (24) and highlight the difficulties in expansion due to labor-intensive preparatory work and the high cost and regulations associated with shipping drug-resistant isolates (27).Criteria for a verification ("fit for purpose") and EQA program suited to the characteristics of the Xpert MTB/RIF assay (3, 8) will require the following elements. (i) The testing material must contain whole M. tuberculosis (8).(ii) Transportation of EQA material needs to be safe. (iii) The testing procedure needs to be safe and compatible with the Xpert MTB/ RIF current testing protocol. (iv) Health care workers who do not have laboratory skills must be able to perform the testing in nonlaboratory settings. (v) Finally, the programs will need to be cost-effective and sustainable. Such a program using whole inactivated M. tuberculosis spotted onto filter paper was developed and piloted in South Africa as part of the National Health Laboratory Service (NHLS) GX rollout. H37Ra]) and well-characterized local clinical strain MYCTU 15, and (iii) the ATCC 25618 (H37Rv) laboratory strain grown for single-cell-organism suspensions (11). The MGIT cultures S-MYCTU-02-P2 and MYCTU 15 and clinical isolates were pooled in their respective batches (with strains kept separate and not mixed), centrifuged (3,000 ϫ g for 15 min at 4°C) to pellet cells, and resuspended in 40 ml phosphate-buffered saline (PBS) followed by addition of 80 ml (2:1 ratio of buffer to culture) of the Xpert sample reagent (SR) buffer. For the H37Rv strain, 200 ml of culture was harvested (by centrifugation at 3,500 ϫ g) at room temperature for 10 min, and cells were resuspended in PBS to 40 ml followed by addition of 80 ml SR buffer (2:1 ratio of buffer to cells). Both MGIT-grown and H37Rv strain cultures were inactivated in SR buffer for 2 h at room temperature, with intermittent mixing. The inactivated material was washed twice with sterile PBS and resuspended in final volumes of 10 ml (S-MYCTU-02-P2 and MYCTU 15) and 40 ml (H37Rv) PBS. For confirmation of inactivation, washed cultures (0.5 ml) were reinoculated into new MGIT tubes in Bactec cabinets fo...

Adoption of POCT accelerated ART initiation but once on treatment, there was unexpectedly higher loss to follow-up on POC and no improvement in outcomes at 12 months over SOC.

The high LTBI incidence and the association of incident LTBI with annual TB caseload among HCWs indicate that more effective TB infection control should be implemented in South African health care facilities.

Background: Human immunodeficiency virus self-testing (HIVST) reduces barriers associated with facility-based testing; however, no formal mechanism exists for users to self-report results or link to care. The AspectTM HIVST mobile application (app) was developed for use in South Africa.Objectives: This study evaluated the acceptability and feasibility of the AspectTM HIVST app for individuals from the inner city of Johannesburg.Method: This cross-sectional pilot, with a convenience sample of 300 adults, was conducted in July 2018. Participants were provided an OraQuick HIVST kit and a smartphone preloaded with the app, then asked to follow the in-app instructions for use (IFU) to complete the HIVST and upload results. Trained healthcare workers (HCWs) observed and recorded any deviations from the IFU, and conducted a post-test survey to assess acceptability. Feasibility was evaluated by the number of participants who agreed to participate, completed the self-test, and uploaded all information onto the app correctly.Results: Most participants (98.7%) found the app easy to use. To reduce difficulties related to the IFU (26; 8.7%), participants suggested multimedia supplements (4; 1.3%), additional languages (4; 1.3%) and simplified instructions (5; 1.7%). All individuals approached, agreed to participate, 267 (89.0%) correctly completed all steps and 210 (78.7%) successfully captured all information on the app. Most errors (26; 8.7%) were testing errors and 1 (0.3%) was from the app sequence. Twelve (4.5%) errors were with test strip imaging and 72 (27.0%) discordances were with demographic information.Conclusion: Despite some challenges with IFU interpretation and data capture via the app, this pilot showed that the AspectTM HIVST app is an acceptable way to upload mobile HIVST results and demographic information to a central database.

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