A case study of delayed HIV-1 seroconversion highlights the need for Combo assays

Skidmore, Susan J.; Devendra, Senan; Weaver, Janelle; Short, J. A.; Osman, Husam; Smit, Erasmus

doi:10.1258/ijsa.2008.008263

Cited by 6 publications

(5 citation statements)

References 6 publications

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“…1 Indeterminate Western blot profiles are described as late as 12 months following infection confirmed by direct detection of HIV-1 proviral DNA. 2 Delayed HIV-1 Western blot positivity is rare and has been associated with malnutrition, 3 profound immunosuppression, 4 opportunistic infection, 4 early ART, 5 HIV-1 elite controllers, 6 humoral immunodeficiency 2 and HIV-2 infection. 7 In our patient two of these features, namely malnutrition and profound immunodeficiency, were present.…”

Section: Discussionmentioning

confidence: 99%

A case of HIV-1 slow seroconversion: diagnostic implications

et al. 2013

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Section: Discussionmentioning

confidence: 99%

A case of HIV-1 slow seroconversion: diagnostic implications

et al. 2013

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“…Branson [10] and Skidmore et al [37] also recommend the use of this assay for improved HIV screening outcomes and earlier detection of HIV, especially of acute cases and in settings of delayed seroconversion. These assays are therefore an appropriate tool for HIV screening in clinical trials.…”

Section: Discussionmentioning

confidence: 99%

“…Unusual diagnostic results of HIV infection have been previously described, including delayed seroconversion and negative HIV PCR results [37]–[41].…”

Section: Discussionmentioning

confidence: 99%

The Implementation and Appraisal of a Novel Confirmatory HIV-1 Testing Algorithm in the Microbicides Development Programme 301 Trial (MDP301)

et al. 2012

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We describe the application of a novel HIV confirmatory testing algorithm to determine the primary efficacy endpoint in a large Phase III microbicide trial. 9385 women were enrolled between 2005 and 2009. Of these women, 537 (6%) had at least one positive HIV rapid test after enrolment. This triggered the use of the algorithm which made use of archived serum and Buffy Coat samples. The overall sample set was >95% complete. 419 (78%) of the rapid test positive samples were confirmed as primary endpoints using a combination of assays for the detection of HIV-specific antibodies (EIA's and Western Blot), and for components of the virus itself (PCR for the detection of nucleic acids and EIA for p24 antigen). 63 (12%) cases were confirmed as being HIV-positive at screening or enrolment and 55 (10%) were confirmed as HIV negative. The testing algorithm confirmed the endpoint at the same visit as that of the first positive rapid test in 90% of cases and at the time of the preceding visit in 10% of cases. Of the 63 cases which were subsequently confirmed to be HIV-1 positive at or before enrolment, 54 specimens contained no detectable HIV antibodies at screening or enrolment. However, 43 were positive using an EIA which detects both HIV antigen and antibody and also had a positive p24 antigen or HIV PCR test, which was highly suggestive of acute infection. There were 6 unusual cases which had undetectable HIV-1 DNA or RNA. In 4 of the 6 cases the presence of HIV-1-specific antibodies was confirmed by Western Blot. One of these cases with an indeterminate Western Blot was a previous vaccine trial participant. The algorithm served the objectives of the study well and can be recommended for use in determining HIV as an endpoint in clinical trials.Trial RegistrationISRCTN.org ISRCTN 64716212

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“…[21] have demonstrated equivalent analytical sensitivities for the HCV NS3 antigen assay and MP‐NAT. For HIV‐1, there is still a small difference of approximately 10 days in the diagnostic window period between the HIV combination assays [22,23] and MP‐NAT.…”

Section: Blood Donor Screening At the German Red Cross Blood Donor Sementioning

confidence: 99%

Current concepts in serological testing – TTID

Schmidt

Seifried

2011

ISBT Science Series

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Introduction Blood components play a major part in a huge number of therapeutic interventions in oncology, haematology, surgery and other medicine disciplines. Therefore, the supply of safe blood products is a major ongoing challenge for blood transfusion services. Serology screening tests were developed to improve blood safety. As screening for antibodies reflects an immune reaction in response to infection, the diagnostic window period is longer for antibody tests than for direct screening assays, such as nucleic amplification tests (NAT). The introduction of mini-pool NAT (MP-NAT) and individual donation NAT (ID-NAT) as well as the development of antigen screening assays, such as the hepatitis C virus antigen test (which detects the NS3 antigen) and the p24 antigen assay for HIV-1, have been able to reduce the diagnostic window period.Methods Currently, blood donor screening for HBsAg, anti-HBc, anti-HCV, anti-HIV-1 ⁄ 2 and syphilis antibodies is mandated by the German authority (the Paul Ehrlich Institute). All blood donations must also be screened for HCV and HIV-1 using MP-NAT. The German Red Cross Blood Donor Services Baden-Wü rttembergHessen has implemented additional blood donor screening for anti-CMV (for platelet products from repeat donors) and MP-NAT screening for HBV, HAV and Parvovirus B19 on a voluntary basis.Results The epidemiology data within the last 4 years have found that 98% and 89% of hepatitis B and hepatitis C positive donors belonged to the first time donor population. Between 1997 and 2005, the German Red Cross Blood Donor Services detected hepatitis B, hepatitis C and HIV-1 in 43, 23 and 7 donors, respectively, using NAT. About 50% (22 out of 43) of these HBV-infected donors were in the acute phase of infection, while 21 were in the occult phase. Improvements in NAT technology, especially the introduction of full-automated extraction robot systems (e.g. the Zelos · 100), have been able to reduce the diagnostic window period, especially for hepatitis B, by improving the 95% level of detection. Nevertheless, five cases of NAT failures in detecting HIV-1 have been reported to the Paul-Ehrlich-Institute within the last decade. In 2010 in particular, three cases occurred in Germany due to mutations in the primer and probe binding regions. These cases restarted a discussion about risk analysis for NAT screening tests and serology methods in general.Conclusion In Germany, blood donor screening is performed using parallel serological assays (antigen and antibody detection) and by MP-NAT for hepatitis B, hepatitis C and HIV-1. The risk of false-negative test results due to mutations in primer and probe binding regions is higher for NAT systems than for antibody ⁄ antigen detection tests. Therefore, the manufactures of the NAT systems are advised to improve their systems by utilising amplification in at least two conserved regions (dual-or triple-targeting). The diagnostic window period for new screening strategies (e.g., antigen screening for HCV) is equal to that of MP-NAT. Improving the per...

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A case study of delayed HIV-1 seroconversion highlights the need for Combo assays

Cited by 6 publications

References 6 publications

A case of HIV-1 slow seroconversion: diagnostic implications

A case of HIV-1 slow seroconversion: diagnostic implications

The Implementation and Appraisal of a Novel Confirmatory HIV-1 Testing Algorithm in the Microbicides Development Programme 301 Trial (MDP301)

Current concepts in serological testing – TTID

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