Laboratory Reflex and Clinic-based Point-of-care Cryptococcal Antigen Screening for Preventing Meningitis and Mortality among People Living with HIV.

Abstract

INTRODUCTION\nCryptococcosis remains a leading cause of meningitis and mortality among people living with HIV (PLHIV) worldwide. We sought to evaluate laboratory-based cryptococcal antigen (CrAg) reflex testing and a clinic-based point-of-care (POC) CrAg screening intervention for preventing meningitis and mortality among PLHIV in South Africa.\n\n\nMETHODS\nWe conducted a prospective pre-post intervention study of adults presenting for HIV testing in Umlazi Township, South Africa over a six-year period (2013-2019). Participants were enrolled during three phases of CrAg testing - CrAg testing ordered by a clinician ( Clinician-directed testing ; 2013-2015); routine lab-based CrAg reflex testing for blood samples with CD4 ≤100 cells/mm3 ( Lab reflex testing ; 2015-2017), and a clinic-based intervention with POC CD4 testing and POC CrAg testing for PLHIV with CD4 ≤200 cells/mm3 with continued standard-of-care routine lab-reflex testing among those with CD4 ≤100 cells/mm3 ( Clinic-based testing ; 2017-2019). The laboratory and clinical teams performed serum CrAg by enzyme immunoassay and lateral flow assay (Immy Diagnostics, Norman, USA). We followed participants for up to 14 months to compare associations between baseline CrAg positivity, ART and fluconazole treatment initiation, and outcomes of cryptococcal meningitis, hospitalization and mortality.\n\n\nRESULTS\n3,105 (39.4%) of 7,877 people screened were HIV-positive, of whom 908 had CD4 ≤200 cells/mm3 and were included in analyses. Lab reflex and clinic-based testing increased CrAg screening (p<0.001) and diagnosis of CrAg-positive PLHIV (p=0.011). As compared to clinician-directed testing, clinic-based CrAg testing increased the number of PLHIV diagnosed with cryptococcal meningitis (4.5% compared to 1.5%; p=0.059), initiation of fluconazole pre-emptive therapy (7.2% compared to 2.5%; p=0.010), and initiation of ART (96.8% compared to 91.3%; p=0.012). Comparing clinic-based testing to lab reflex testing, there was no significant difference in the cumulative incidence of cryptococcal meningitis (4.5% compared to 4.1%; p=0.836) or mortality (8.1% compared to 9.9%; p=0.557).\n\n\nCONCLUSIONS\nLab reflex and clinic-based CrAg testing facilitated diagnosis of HIV-associated cryptococcosis and fluconazole initiation, but did not reduce cryptococcal meningitis or mortality. In this non-randomized cohort, clinical outcomes were similar between lab reflex testing and clinic-based point-of-care CrAg testing.