Point-of-care viral load tests to detect high HIV viral load in people living with HIV/AIDS attending health facilities.

BACKGROUND: Viral load (VL) testing in people living with HIV (PLHIV) helps to monitor antiretroviral therapy (ART). VL is still largely tested using central laboratory-based platforms, which have long test turnaround times and involve sophisticated equipment. VL tests with point-of-care (POC) platforms capable of being used near the patient are potentially easy to use, give quick results, are cost-effective, and could replace central or reference VL testing platforms. OBJECTIVES: To estimate the diagnostic accuracy of POC tests to detect high viral load levels in PLHIV attending healthcare facilities. SEARCH METHODS: We searched eight electronic databases using standard, extensive Cochrane search methods, and did not use any language, document type, or publication status limitations. We also searched the reference lists of included studies and relevant systematic reviews, and consulted an expert in the field from the World Health Organization (WHO) HIV Department for potentially relevant studies. The latest search was 23 November 2020. SELECTION CRITERIA: We included any primary study that compared the results of a VL test with a POC platform to that of a central laboratory-based reference test to detect high viral load in PLHIV on HIV/AIDS care or follow-up. We included all forms of POC tests for VL as defined by study authors, regardless of the healthcare facility in which the test was conducted. We excluded diagnostic case-control studies with healthy controls and studies that did not provide sufficient data to create the 2 × 2 tables to calculate sensitivity and specificity. We did not limit our study inclusion to age, gender, or geographical setting. DATA COLLECTION AND ANALYSIS: Two review authors independently screened the titles, abstracts, and full texts of the search results to identify eligible articles. They also independently extracted data using a standardized data extraction form and conducted risk of bias assessment using the Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) tool. Using participants as the unit of analysis, we fitted simplified univariable models for sensitivity and specificity separately, employing a random-effects model to estimate the summary sensitivity and specificity at the current and commonly reported World Health Organization (WHO) threshold (≥ 1000 copies/mL). The bivariate models did not converge to give a model estimate. MAIN RESULTS: We identified 18 studies (24 evaluations, 10,034 participants) defining high viral loads at main thresholds ≥ 1000 copies/mL (n = 20), ≥ 5000 copies/mL (n = 1), and ≥ 40 copies/mL (n = 3). All evaluations were done on samples from PLHIV retrieved from routine HIV/AIDS care centres or health facilities. For clinical applicability, we included 14 studies (20 evaluations, 8659 participants) assessing high viral load at the clinical threshold of ≥ 1000 copies/mL in the meta-analyses. Of these, sub-Saharan Africa, Europe, and Asia contributed 16, three, and one evaluation respectively. All included participants were on ART in only nine evaluations; in the other 11 evaluations the proportion of participants on ART was either partial or not clearly stated. Thirteen evaluations included adults only (n = 13), five mixed populations of adults and children, whilst in the remaining two the age of included populations was not clearly stated. The majority of evaluations included commercially available tests (n = 18). Ten evaluations were POC VL tests conducted near the patient in a peripheral or onsite laboratory, whilst the other 10 were evaluations of POC VL tests in a central or reference laboratory setting. The test types evaluated as POC VL tests included Xpert HIV-1 Viral Load test (n = 8), SAMBA HIV-1 Semi-Q Test (n = 9), Alere Q NAT prototype assay for HIV-1 (n = 2) and m-PIMA HIV-1/2 Viral Load test (n = 1). The majority of evaluations (n = 17) used plasma samples, whilst the rest (n = 3) utilized whole blood samples. Pooled sensitivity (95% confidence interval (CI)) of POC VL at a threshold of ≥ 1000 copies/mL was 96.6% (94.8 to 97.8) (20 evaluations, 2522 participants), and pooled specificity (95% CI) was 95.7% (90.8 to 98.0) (20 evaluations, 6137 participants). Median prevalence for high viral load (≥ 1000 copies/mL) (n = 20) was 33.4% (range 6.9% to 88.5%). Limitations The risk of bias was mostly assessed as unclear across the four domains due to incomplete reporting. AUTHORS' CONCLUSIONS: We found POC VL to have high sensitivity and high specificity for the diagnosis of high HIV viral load in PLHIV attending healthcare facilities at a clinical threshold of ≥ 1000 copies/mL.

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.

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.

At what times during infection is SARS-CoV-2 detectable and no longer detectable using RT-PCR-based tests? A systematic review of individual participant data.

BACKGROUND: Tests for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral ribonucleic acid (RNA) using reverse transcription polymerase chain reaction (RT-PCR) are pivotal to detecting current coronavirus disease (COVID-19) and duration of detectable virus indicating potential for infectivity. METHODS: We conducted an individual participant data (IPD) systematic review of longitudinal studies of RT-PCR test results in symptomatic SARS-CoV-2. We searched PubMed, LitCOVID, medRxiv, and COVID-19 Living Evidence databases. We assessed risk of bias using a QUADAS-2 adaptation. Outcomes were the percentage of positive test results by time and the duration of detectable virus, by anatomical sampling sites. RESULTS: Of 5078 studies screened, we included 32 studies with 1023 SARS-CoV-2 infected participants and 1619 test results, from - 6 to 66 days post-symptom onset and hospitalisation. The highest percentage virus detection was from nasopharyngeal sampling between 0 and 4 days post-symptom onset at 89% (95% confidence interval (CI) 83 to 93) dropping to 54% (95% CI 47 to 61) after 10 to 14 days. On average, duration of detectable virus was longer with lower respiratory tract (LRT) sampling than upper respiratory tract (URT). Duration of faecal and respiratory tract virus detection varied greatly within individual participants. In some participants, virus was still detectable at 46 days post-symptom onset. CONCLUSIONS: RT-PCR misses detection of people with SARS-CoV-2 infection; early sampling minimises false negative diagnoses. Beyond 10 days post-symptom onset, lower RT or faecal testing may be preferred sampling sites. The included studies are open to substantial risk of bias, so the positivity rates are probably overestimated.