Should Urine-LAM Tests Be Used in TB Symptomatic HIV-Positive Patients When No CD4 Count Is Available? A Prospective Observational Cohort Study From Malawi.

BACKGROUND: Current eligibility criteria for urine lateral-flow lipoarabinomannan assay (LF-LAM) in ambulatory, HIV-positive patients rely on the CD4 count. We investigated the diagnostic yield of LF-LAM and the 6-month mortality in ambulatory, TB symptomatic, HIV-positive patients regardless of their CD4 count. METHODS: We conducted a prospective, observational study that included all ambulatory, ≥15-year-old, TB symptomatic (cough, weight loss, fever, or night sweats) HIV-positive patients presenting at 4 health facilities in Malawi. Patients received a clinical examination and were requested urine LF-LAM, sputum microscopy, and Xpert MTB/RIF. TB was defined as bacteriologically confirmed if Xpert was positive. RESULTS: Of 485 patients included, 171 (35.3%) had a CD4 <200 and 32 (7.2%) were seriously ill. Median CD4 count was 341 cells/µL (interquartile range: 129-546). LAM was positive in 24.9% patients with CD4 < 200 (50% LAM grades 2-4) and 12.5% with CD4 ≥ 200 (12.8% LAM grades 2-4). Xpert was positive in 14.1% (44/312). Among Xpert-positive patients, LAM positivity was 56.7% (CD4 < 200) and 42.9% (CD4 ≥ 200), P = 0.393. Of the patients without an Xpert result, 13.4% (23/172) were LAM positive (ie, potentially missed patients). Overall, mortality was 9.2% (44/478). More pronounced LAM-positive patients had higher mortality than LAM-negative (grades 2-4: 36.0%; grade 1: 9.1%; negative: 7.4%; P < 0.001). LAM-positive patients with CD4 <200 cells/µL had higher risk of mortality than LAM negatives (adjusted hazard ratio: 3.2, 95% confidence interval: 1.4 to 7.2, P = 0.006), particularly those with LAM grades 2-4 (adjusted hazard ratio: 4.9, 95% confidence interval: 1.8 to 13.3, P = 0.002). CONCLUSIONS: Urine-LAM testing can be useful for TB diagnosis in HIV-positive TB-symptomatic patients with no CD4 cell count. LAM grade can identify patients at higher risk of death in this situation.

Point-of-care viral load monitoring: outcomes from a decentralized HIV programme in Malawi.

INTRODUCTION: Routinely monitoring the HIV viral load (VL) of people living with HIV (PLHIV) on anti-retroviral therapy (ART) facilitates intensive adherence counselling and faster ART regimen switch when treatment failure is indicated. Yet standard VL-testing in centralized laboratories can be time-intensive and logistically difficult in low-resource settings. This paper evaluates the outcomes of the first four years of routine VL-monitoring using Point-of-Care technology, implemented by Médecins Sans Frontières (MSF) in rural clinics in Malawi. METHODS: We conducted a retrospective cohort analysis of patients eligible for routine VL- testing between 2013 and 2017 in four decentralized ART-clinics and the district hospital in Chiradzulu, Malawi. We assessed VL-testing coverage and the treatment failure cascade (from suspected failure (first VL>1000 copies/mL) to VL suppression post regimen switch). We used descriptive statistics and multivariate logistic regression to assess factors associated with suspected failure. RESULTS AND DISCUSSION: Among 21,400 eligible patients, VL-testing coverage was 85% and VL suppression was found in 89% of those tested. In the decentralized clinics, 88% of test results were reviewed on the same day as blood collection, whereas in the district hospital the median turnaround-time for results was 85 days. Among first-line ART patients with suspected failure (N = 1544), 30% suppressed (VL<1000 copies/mL), 35% were treatment failures (confirmed by subsequent VL-testing) and 35% had incomplete VL follow-up. Among treatment failures, 80% (N = 540) were switched to a second-line regimen, with a higher switching rate in the decentralized clinics than in the district hospital (86% vs. 67%, p < 0.01) and a shorter median time-to-switch (6.8 months vs. 9.7 months, p < 0.01). Similarly, the post-switch VL-testing rate was markedly higher in the decentralized clinics (61% vs. 26%, p < 0.01). Overall, 79% of patients with a post-switch VL-test were suppressed. CONCLUSIONS: Viral load testing at the point-of-care in Chiradzulu, Malawi achieved high coverage and good drug regimen switch rates among those identified as treatment failures. In decentralized clinics, same-day test results and shorter time-to-switch illustrated the game-changing potential of POC-based VL-testing. Nevertheless, gaps were identified along all steps of the failure cascade. Regular staff training, continuous monitoring and creating demand are essential to the success of routine VL-testing.

Diagnostic value of the urine lipoarabinomannan assay in HIV-positive, ambulatory patients with CD4 below 200 cells/µl in 2 low-resource settings: A prospective observational study.

BACKGROUND: Current guidelines recommend the use of the lateral flow urine lipoarabinomannan assay (LAM) in HIV-positive, ambulatory patients with signs and symptoms of tuberculosis (TB) only if they are seriously ill or have CD4 count ≤ 100 cells/µl. We assessed the diagnostic yield of including LAM in TB diagnostic algorithms in HIV-positive, ambulatory patients with CD4 < 200 cells/µl, as well as the risk of mortality in LAM-positive patients who were not diagnosed using other diagnostic tools and not treated for TB. METHODS AND FINDINGS: We conducted a prospective observational study including HIV-positive adult patients with signs and symptoms of TB and CD4 < 200 cells/µl attending 6 health facilities in Malawi and Mozambique. Patients were included consecutively from 18 September 2015 to 27 October 2016 in Malawi and from 3 December 2014 to 22 August 2016 in Mozambique. All patients had a clinical exam and LAM, chest X-ray, sputum microscopy, and Xpert MTB/RIF assay (Xpert) requested. Culture in sputum was done for a subset of patients. The diagnostic yield was defined as the proportion of patients with a positive assay result among those with laboratory-confirmed TB. For the 456 patients included in the study, the median age was 36 years (IQR 31-43) and the median CD4 count was 50 cells/µl (IQR 21-108). Forty-five percent (205/456) of the patients had laboratory-confirmed TB. The diagnostic yields of LAM, microscopy, and Xpert were 82.4% (169/205), 33.7% (69/205), and 40.0% (84/205), respectively. In total, 50.2% (103/205) of the patients with laboratory-confirmed TB were diagnosed only through LAM. Overall, the use of LAM in diagnostic algorithms increased the yield of algorithms with microscopy and with Xpert by 38.0% (78/205) and 34.6% (71/205), respectively, and, specifically among patients with CD4 100-199 cells/µl, by 27.5% (14/51) and 29.4% (15/51), respectively. LAM-positive patients not diagnosed through other tools and not treated for TB had a significantly higher risk of mortality than LAM-positive patients who received treatment (adjusted risk ratio 2.57, 95% CI 1.27-5.19, p = 0.009). Although the TB diagnostic conditions in the study sites were similar to those in other resource-limited settings, the added value of LAM may depend on the availability of microscopy or Xpert results. CONCLUSIONS: LAM has diagnostic value for identifying TB in HIV-positive patients with signs and symptoms of TB and advanced immunodeficiency, including those with a CD4 count of 100-199 cells/µl. In this study, the use of LAM enabled the diagnosis of TB in half of the patients with confirmed TB disease; without LAM, these patients would have been missed. The rapid identification and treatment of TB enabled by LAM may decrease overall mortality risk for these patients.

The Development of a Multilingual Tool for Facilitating the Primary-Specialty Care Interface in Low Resource Settings: the MSF Tele-Expertise System.

In 2009, Médecins Sans Frontières (MSF) started a pilot trial of store-and-forward telemedicine to support field workers. One network was operated in French and one in English; a third, Spanish network was brought into operation in 2012. The three telemedicine pilots were then combined to form a single multilingual tele-expertise system, tailored to support MSF field staff. We conducted a retrospective analysis of all telemedicine cases referred from April 2010 to March 2014. We also carried out a survey of all users in December 2013. A total of 1039 referrals were received from 41 countries, of which 89% were in English, 10% in French, and 1% in Spanish. The cases covered a very wide range of medical and surgical specialties. The median delay in providing the first specialist response to the referrer was 5.3 h (interquartile range 1.8, 16.4). The survey was sent to 294 referrers and 254 specialists. Of these, 224 were considered as active users (41%). Out of the 548 users, 163 (30%) answered the survey. The majority of referrers (79%) reported that the advice received via the system improved their management of the patient. The main concerns raised by referrers and specialists were the lack of support or promotion of system at headquarters' level and the lack of feedback about patient follow-up. Because of the size of the MSF organization, it is clear that there is potential for further organizational adoption.