Laboratory Evaluation of the Alere q Point-of-Care System for Early Infant HIV Diagnosis

Abstract

IntroductionEarly infant diagnosis (EID) and prompt linkage to care are critical to minimise the high morbidity and mortality associated with infant HIV infection. Attrition in the “EID cascade” is common; however, point-of-care (POC) EID assays with same-day result could facilitate prompt linkage of HIV-infected infant to treatment. Despite a number of POC EID assays in development, few have been independently evaluated and data on new technologies are urgently needed to inform policy.MethodsWe compared Alere q 1/2 Detect POC system laboratory test characteristics with the local standard of care (SOC), Roche CAP/CTM HIV-1 qualitative PCR in an independent laboratory-based evaluation in Cape Town, South Africa. Routinely EID samples collected between November 2013 and September 2014 were each tested by both SOC and POC systems. Repeat testing was done to troubleshoot any discrepancy between POC and SOC results.ResultsOverall, 1098 children with a median age of 47 days (IQR, 42–117) were included. Birth PCR (age <7 days) comprised of 8% (n = 92) tests while 56% (n = 620) of children tested as part of routine EID (ages 6–14 weeks). In the overall direct comparison, Alere q Detect achieved sensitivity of 95.5% (95% CI, 91.7–97.9%) and a specificity of 99.8% (95% CI, 99.1–100%). Following repeat testing of discordant samples and exclusion of any inconclusive results, the POC assay sensitivity and specificity were 96.9% (95% CI 93.4–98.9%) and 100% (lower 95% CI 98%) respectively. Among birth PCR tests the POC assay had slightly lower sensitivity (93.3% vs 96.5% in routine EID) and higher assay error rate (10% vs 5% in samples of older children, p = 0.04).ConclusionOur results indicate this POC assay performs well for EID in the laboratory. The high specificity and thus high positive predictive value would suggest a positive POC result may be adequate for immediate infant ART initiation. While POC testing for EID may have particular utility for birth testing at delivery facilities, the lower sensitivity and error rate requires further attention, as does field implementation of POC EID technologies in other clinical care settings.

Xpert HIV-1 point-of-care test for neonatal diagnosis of HIV in the birth testing programme of a maternity hospital: a field evaluation study

“…16 Repeating the POCT on the same sample reduced the error rate to 0.5%. Closer analysis of the POCT errors revealed many modifiable factors.…”

“…While there is some laboratory evaluation data available, 11–14 field evaluations of POCT platforms for EID, particularly at birth, are required prior to implementation. The Alere Q NAT test (Alere Technologies, Jena, Germany) has been shown to perform at a sensitivity of 98.5% (Jani et al, no neonates) 15 and 96.5% overall (93.3% in 92 neonates, Hsiao et al; 99% in 291 neonates, Kroon et al) 16,17 with specificity >99.5% and there are few published data for Cepheid EID POCT in infants or neonates including the EID consortium which gathers data on neonates and infants. 18 …”

Brief Report: High Sensitivity and Specificity of the Cepheid Xpert HIV-1 Qualitative Point-of-Care Test Among Newborns in Botswana

“…10,11 Nevertheless, our slightly reduced sensitivity at birth to 93.3% is consistent with similarly reduced sensitivities of other POC platforms in children less than 3 days of age. 15,16 …”

Detection and differentiation of HIV-2 using the point-of-care Alere q HIV-1/2 Detect nucleic acid test

“…The Alere Detect test was first investigated for early infant detection (EID) in Mozambique and South Africa (19, 20). In these two studies, heel-stick blood samples were tested by the Alere Detect test and the Roche COBAS® AmpliPrep/COBAS® TaqMan® HIV-1 Qualitative Test (Roche HIV-1 qualitative test).…”

“…The Alere q HIV-1/-2 Detect (Alere Detect) test is a rapid point-of-care (POC) nucleic acid test (NAT) providing several advantageous characteristics for HIV diagnosis: 1) the requirement for only 25 microliters plasma or whole blood per test; 2) test completion within one hour; 3) detection and differentiation of HIV-1 Group M/N, HIV-1 Group O and HIV-2 nucleic acid; and 4) the only currently available POC NAT able to detect HIV-2 (18). Two studies have demonstrated the feasibility of the Alere Detect test to diagnose HIV-1 infection for HIV-1-exposed infants in South Africa and Mozambique (19, 20). Here, we evaluated the performance of the Alere Detect test for the detection of HIV-1 and HIV-2 in plasma samples collected from HIV-1, HIV-2 and differentiation of HIV-1 from HIV-2, in dually-seropositive patients.…”