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Investigation of the Pathophysiology and Diagnostic Methods Through a Case of Acute HIV Infection in which the Western Blot Method Remained Negative Over the Long Term and the 4th Generation Screening Assay Became Negative for a Certain Period of Time after Initiating Antiretroviral Therapy
1)Department of Laboratory Medicine, Tokyo Medical University Hospital, 2)Department of Infection Control, Kanto Rosai Hospital, 3)Department of Infectious Diseases, Toranomon Hospital, 4)Department of Infectious Diseases and Applied Immunology, The University of Tokyo IMSUT Hospital of The Institute of Medical Science, 5)Department of Microbiology and Immunology, Keio University, 6)Department of Infection and Immunology, Nagoya Medical Center Clinical Research Center, 7)Infectious Disease and Immunology Development and Medical Affairs Division, GlaxoSmithKline K.K.
Kazuki NIWA1)2), Yasuyuki YAMAMOTO1), Mihoko YOTSUMOTO1), Yushi CHIKASAWA1), Masato BINGO1), Takashi MURAMATSU1), Ikuo SEITA1), Manabu OTAKI1), Kyoichi OGATA1), Tsuyoshi HAGIWARA1), Takashi SUZUKI1), Kagehiro AMANO1), Muneyoshi KIMURA3), Akiko YONEYAMA3), Saho TAKAYA4), Tomohiko KOIBUCHI4), Shingo KATO5), Reiko OKAZAKI6), Atsuko HACHIYA6), Wataru SUGIURA7) & Katsuyuki FUKUTAKE1)
(Received January 12, 2016)
(Accepted October 12, 2016)
Key words: HIV, Western blot assay, HIV1/2 fourth-generation immunoassay, diagnosis, guideline

Confirmatory tests using Western blot (WB) and HIV-1 nucleic acid testing (HIV-1 RNA) following a positive screening test are required for the diagnosis of HIV-1 infection according to the current Japanese guidelines for HIV-1/2 diagnosis. We report herein on a rare case in a patient who remained negative for WB over 10 months in spite of being positive by fourth-generation immunoassays (4thGIA) and who subsequently seroreverted by 4thGIA for three months after initiating antiretroviral therapy.

Case: A man in his early twenties previously visited a hospital because of fever in October 2012. Laboratory data revealed leukocytopenia, thrombocytopenia and increased serum ferritin, suggesting hemophagocytic syndrome (HPS). During that visit, he tested positive for a 4thGIA, but negative for HIV-1 WB and his result of HIV-1 RNA result was detected invalid because of the presence of some inhibitory material in his RNA preparation. Thereafter, he was diagnosed as having cytomegalovirus-associated HPS treatment was for which initiated. In January 2013, he developed Pneumocystis jirovecii pneumonia, and his HIV-1 RNA viral load was 7.7 × 105 copies/mL in February 2013. Acute HIV infection was suspected, because the HIV-1 WB remained negative. He was started on antiretroviral therapy in April 2013. His 4thGIA was converted to negative in May 2013 and was reconverted to positive in August 2013. HIV-1 WB, however, continued to be indeterminant until February 2014, in which it turned positive for the first time according to the CDC criteria.

Methods and Results: The genetic analyses of HIV-1 were done on the gag, env, nef and pol region of the HIV-1 gene from the patient. There was no clear element to delay antibody production on the virus side. Preserved specimens of the patient were measured with eight kinds of HIV screening assay. It was thought that the fourth generation assay was positive only by the presence of the antigen until March 2013 because the antibody had not been detected.

Discussion: We encountered a case of acute HIV infection in which the WB result was negative for 10 months after the first positive response of the 4thGIA. The 4thGIA is essential for the early diagnosis and early treatment of HIV infection; therefore, the 4thGIA should be strictly recommended to avoid the use of older generations of immunoassay in the diagnostic guidelines. The role of the WB test should be examined closely from various aspects for use as a confirmatory test under recent laboratory situations in which highly sensitive and specific methods, e.g. the 4th GIA, have become available. In addition, unnecessary confusion due to the diversities of antibody formation should be avoided. The antibody detection tests for HIV are still necessary and indispensable for the confirmation of the disease or the diagnosis of the acute infection stage. Therefore development of a newer antibody measuring method which could achieve an easier operation and should have a higher sensitivity and specificity for HIV confirmation is strongly expected.

[ Kansenshogaku Zasshi 91: 7-13, 2017 ]

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