As no scientific evaluation was provided by these websites or found in literature, we wished to determine the performance of such tests, which are not CE-marked, FDA-approved, or WHO prequalified, on our extensive panel. or primary infection, was highly variable, depending on the test. One of the two 4G tests allowed detection of additional positive samples from early stages of infection, whereas the second (sold as Ipragliflozin a 4G test on a website) corresponded in reality to a 3G test. Interpretation Our study showed that not all tests are equal for the detection of major HIV variants or early stages of HIV infection; adding the detection of specific p24Ag improved the latter point. This study also showed, for the first time, that buying through web-based vendors can be risky, due to the varying performance of the tests and questionable sales Ipragliflozin practices. Our results are of particular importance in the context of the increasing use of rapid tests in an outside laboratory settings. Fund Sant Publique France, COREVIH C Normandie, and Rouen University Hospital. Research in context Evidence before this study HIV rapid tests are unitary assays used in clinical and non-clinical settings; they facilitate screening of HIV infection due to their technical simplicity and rapid results. The World Health Organisation (WHO) encourages more widespread use of these tests, in particular to extend HIV self-testing. Real-life surveillance of test performance has shown it to be affected by the clinical status of the patient, the genetic nature of the variant responsible for the infection, or the tested population. Many tests are available which may be CE-marked, FDA-approved, WHO prequalified, or not. It is thus essential to continuously control the performance of current and new tests. Former evidence was identified by searches of MEDLINE/PubMed references from relevant articles using the search terms rapid diagnostic test, and HIV diagnosis. Abstracts and reports from meetings were included only when they related directly to previously published work. The recommendations and opinions of numerous national and international health organizations and agencies, including the WHO, UNAIDS, ANRS, CDC, ECDC, NIH, and FDA were included. Documents published in English and Ipragliflozin French between 1983 and 2018 were included. Added value of this study We evaluated numerous tests (diagnostic medical devices are essential, particularly for helping nonprofessionals to decide which RSTs/STs to use. For the commercialisation and use of HIV RSTs/STs CE-marking (in Europe), FDA approval (in the US), or WHO prequalification requires performance that matches criteria [[9], [10], [11], [12]] of high sensitivity [100% (CE), 99% (FDA-WHO)] and specificity [(99% (CE-FDA), 98% (WHO)] to avoid a missed diagnosis due to a false-negative result, or an unacceptable false-positive result. Such performance can be guaranteed in the context of these qualifications, but real-life surveillance of test performance has shown it to be affected by the clinical status of the patient, the genetic nature of the variant responsible for the infection, or the tested population, especially in sub-Saharan regions [[13], [14], [15]]. Thus, differences in the sensitivity of 3rd generation (3G) tests, which only detect HIV-1/2 antibodies, have been demonstrated in the early phase of HIV infection [[15], [16], [17]]. Ipragliflozin The development of 4th generation (4G) RSTs, which detect both HIV-1/2 antibodies and HIV-1 p24 antigen (p24Ag), should improve the screening of such infections [18]. However, the first CE-marked/FDA-approved 4G RST, the Determine PIK3R1 HIV-1/2 Ag/Ac Combo assay (Alere/Abbott Chicago Ill), showed limited performance for the specific detection of p24Ag, leading to insufficient added value relative to 3G tests [[19], [20], [21], [22]]. It has also been shown that viral diversity, especially major variants, such as HIV-1 group.