Point‐of‐care tests detecting HIV nucleic acids for diagnosis of HIV‐1 or HIV‐2 infection in infants and children aged 18 months or less

Abstract Background The standard method of diagnosing HIV in infants and children less than 18 months is with a nucleic acid amplification test reverse transcriptase polymerase chain reaction test (NAT RT‐PCR) detecting viral ribonucleic acid (RNA). Laboratory testing using the RT‐PCR platform for HIV infection is limited by poor access, logistical support, and delays in relaying test results and initiating therapy in low‐resource settings. The use of rapid diagnostic tests at or near the point‐of‐care (POC) can increase access to early diagnosis of HIV infection in infants and children less than 18 months of age and timely initiation of antiretroviral therapy (ART). Objectives To summarize the diagnostic accuracy of point‐of‐care nucleic acid‐based testing (POC NAT) to detect HIV‐1/HIV‐2 infection in infants and children aged 18 months or less exposed to HIV infection. Search methods We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (until 2 February 2021), MEDLINE and Embase (until 1 February 2021), and LILACS and Web of Science (until 2 February 2021) with no language or publication status restriction. We also searched conference websites and clinical trial registries, tracked reference lists of included studies and relevant systematic reviews, and consulted experts for potentially eligible studies. Selection criteria We defined POC tests as rapid diagnostic tests conducted at or near the patient site. We included any primary study that compared the results of a POC NAT to a reference standard of laboratory NAT RT‐PCR or total nucleic acid testing to detect the presence or absence of HIV infection denoted by HIV viral nucleic acids in infants and children aged 18 months or less who were exposed to HIV‐1/HIV‐2 infection. We included cross‐sectional, prospective, and retrospective study designs and those that provided sufficient data to create the 2 × 2 table to calculate sensitivity and specificity. We excluded diagnostic case control studies with healthy controls. Data collection and analysis We extracted information on study characteristics using a pretested standardized data extraction form. We used the QUADAS‐2 (Quality Assessment of Diagnostic Accuracy Studies) tool to assess the risk of bias and applicability concerns of the included studies. Two review authors independently selected and assessed the included studies, resolving any disagreements by consensus. The unit of analysis was the participant. We first conducted preliminary exploratory analyses by plotting estimates of sensitivity and specificity from each study on forest plots and in receiver operating characteristic (ROC) space. For the overall meta‐analyses, we pooled estimates of sensitivity and specificity using the bivariate meta‐analysis model at a common threshold (presence or absence of infection). Main results We identified a total of 12 studies (15 evaluations, 15,120 participants). All studies were conducted in sub‐Saharan Africa. The ages of included infants and children in the evaluations were as follows: at birth (n = 6), ≤ 12 months (n = 3), ≤ 18 months (n = 5), and ≤ 24 months (n = 1). Ten evaluations were field evaluations of the POC NAT test at the point of care, and five were laboratory evaluations of the POC NAT tests.The POC NAT tests evaluated included Alere q HIV‐1/2 Detect qualitative test (recently renamed m‐PIMA q HIV‐1/2 Detect qualitative test) (n = 6), Xpert HIV‐1 qualitative test (n = 6), and SAMBA HIV‐1 qualitative test (n = 3). POC NAT pooled sensitivity and specificity (95% confidence interval (CI)) against laboratory reference standard tests were 98.6% (96.1 to 99.5) (15 evaluations, 1728 participants) and 99.9% (99.7 to 99.9) (15 evaluations, 13,392 participants) in infants and children ≤ 18 months. Risk of bias in the included studies was mostly low or unclear due to poor reporting. Five evaluations had some concerns for applicability for the index test, as they were POC tests evaluated in a laboratory setting, but there was no difference detected between settings in sensitivity (−1.3% (95% CI −4.1 to 1.5)); and specificity results were similar. Authors' conclusions For the diagnosis of HIV‐1/HIV‐2 infection, we found the sensitivity and specificity of POC NAT tests to be high in infants and children aged 18 months or less who were exposed to HIV infection.