Next-generation point-of-care testing in pediatric human immunodeficiency virus infection facilitates diagnosis and monitoring of treatment

Abstract

Point-of-care (PoC) testing facilitates early infant diagnosis (EID) and treatment initiation, which improves outcome. We present a field evaluation of a new PoC test (Cepheid Xpert® HIV-1 Qual XC RUO) to determine whether this test improves EID and assists the management of children living with human immunodeficiency virus (HIV) infection. We compared 2 PoC tests with the standard-of-care (SoC) test used to detect HIV infection from dry blood spots in newborn infants at high risk of in utero infection. We also evaluated the ability of the PoC tests to detect HIV total nucleic acid (TNA) in children living with HIV infection who had maintained undetectable plasma viremia following very early combination antiretroviral therapy (cART) initiation. Qualitative (Qual) detection of HIV using the Xpert® HIV-1 Qual XC RUO ("RUO") and Xpert® HIV-1 Qual ("Qual") PoC tests was compared in 224 infants with the SoC DBS Roche COBAS® HIV-1/HIV-2 qualitative test. The same 2 PoC tests were also evaluated in 35 older children who had initiated cART before 21 days of age and maintained undetectable plasma viremia for a mean of 25 months. No discrepancies were observed in detection of HIV infection via the 2 PoC tests or the SoC test in the 224 neonates studied, but only 95% of the SoC test results were generated compared with 100% of the PoC test results (P = .0009). The cycle threshold values for the research use only (RUO) assay were the lowest of the 3 assays (P < .0001 in each case). In 6 of the 35 early-treated aviremic children, HIV TNA was detected by RUO but not Qual. The RUO assay outperforms Qual in detecting HIV-1 infection. RUO would therefore potentially improve EID and assist in identifying cART-adherent early-treated children with the lowest HIV TNA levels and the highest HIV cure potential.

Figure 1.

Comparison of 2 PoC assays with the SoC dried blood spot assay for early infant diagnosis of HIV infection. (A) Study design. Not done*: the reasons why these tests were not done are detailed in the text. (B) Ct values for the 6 infants of 210 infants tested at birth (SoC) or at a median of 20 h of age who tested positive for the 2 PoC assays, Xpert® HIV-1 Qual (“Qual”), Xpert® HIV-1 Qual XC RUO (“RUO”), and the SoC dried blood spot DBS Cobas HIV-1/HIV-2 qualitative test. (C) Ct values for the 12 children who had previously tested positive or indeterminate on the birth DBS assay and who now tested positive at a median of 9.5 days on all 3 assays. In the case of the DBS assay, only 11 of these 12 infants were tested. Ct = cycle threshold, DBS = dry blood spot, HIV = human immunodeficiency virus, PoC = point of care, RUO = research use only, SoC = standard of care.

Figure 2.

Evaluation of PoC testing in early ART-treated children maintaining aviremia for a mean of >24 mo. (A) Ct values for the 2 PoC assays, Xpert® HIV-1 Qual (“Qual”), Xpert® HIV-1 Qual XC RUO (“RUO”), in 22 children who tested positive for both assays. (B) Initial (baseline) DNA viral loads (cpm pbmc: copies per million peripheral blood mononuclear cells) in children who tested positive for the Xpert® HIV-1 Qual XC RUO assay (“positive by RUO test”) versus those who tested negative on the Xpert® HIV-1 Qual XC RUO assay (“positive by RUO test”). (C–E) Three children tested using both PoC assays at consecutive clinic visits 4-mo apart. Gray lines indicate the normal-for-age 10th, 50th, and 90th centiles for absolute CD4 counts in HIV-uninfected children.^[10,11] (C and D) Two children who tested positive on both tests at the first visit and then negative on the Qual test, but still positive on the RUO test, at the next visit. RUO Ct values increased from 38.0 to 40.1 and from 36.7 to 38.7, respectively, between the 2 clinic visits. (E) One child who tested negative on both tests on the first visit and then positive on the RUO test only at the next visit (Ct value 39.2). HIV = human immunodeficiency virus, PoC = point of care, Qual = qualitative, RUO = research use only, SoC = standard of care.