|Title / Titel||Alternative, HIV-1 p24 based viral load test for resource-poor setting — towards a universally usable HIV-1 Viral Protein Load Assay|
|Abstract (PDF, 14 KB)|
|Summary / Zusammenfassung||Measurement of HIV-1 RNA concentration is considered the gold standard for monitoring antiretroviral therapies. Tests are, however, expensive and require technically advanced infrastructure and equipment and highly trained personnel. The increasing availability of antiretroviral treatment in resource-poor settings calls for simple and inexpensive virus tests.
HIV-1 p24 antigen tests were frequently used before the availability of nucleic acid tests (NAT). Three simple modifications, including (i) use of an efficient virus disruption buffer for sample pretreatment, (ii) heat-mediated destruction of antibodies that interfere with the test and (iii) an increased sensitivity achieved by a signal amplification step, have shaped the p24 antigen test into a tool that rivals the performance of NAT in several aspects. All these improvements were first introduced by our group.
Thus, HIV-1 p24 antigen test rivals the PCR for HIV-1 DNA or RNA in HIV-1 subtype B or C settings. In these, the ultrasensitive HIV-1 p24 assay detects pediatric HIV-1 infection as sensitively as does PCR for HIV-1 DNA. The HIV-1 p24 concentration is as predictive of CD4+ T-cell decline, clinical progression and survival in adult patients as is the concentration of HIV-1 RNA. It can be used for viral load monitoring in both adults and children and the HIV-1 p24 concentrations
The goals of this long-term project are
(1) to improve this assay further with respect to its detection limit, its specificity, its capability to detect all the diverse HIV-1 isolates, its precision and ease of handling.
(2) to assess the HIV-1 p24 and HIV-1 RNA (or DNA) in side-by-side comparisons with respect to their suitability for diagnosing pediatric HIV-1 infection, predicting CD4+ changes and disease progression, to monitor the effects of antiretroviral treatment and to detect relevant viral failures.
In these tasks we are collaborating with several other groups, as indicated by the authors and coauthors of our publications.
|Publications / Publikationen||Schüpbach J and Böni J. Quantitative and sensitive detection of immune-complexed and free HIV antigen after boiling of serum. J Virol Methods 1993; 43:247-256.Schüpbach J, Böni J, Tomasik Z, Jendis J, Seger R, Kind C, and the Swiss Neonatal HIV Study Group. Sensitive detection and early prognostic significance of antigen p24 in heat-denatured plasma of human immunodeficiency virus type 1-infected infants. J Infect Dis 1994; 170:318-324.Schüpbach J, Flepp M, Pontelli D, Tomasik Z, Lüthy R, Böni J. Heat-mediated immune complex dissociation and ELISA signal amplification render antigen p24 detection in plasma as sensitive as HIV-1 RNA detection by polymerase chain reaction. AIDS 1996; 10:1085-1090.Böni J, Opravil M, Tomasik Z, Rothen M, Bisset L, Grob PJ, Lüthy R, Schüpbach J. Simple monitoring of antiretroviral therapy with a signal-amplification–boosted human immunodeficiency virus type 1 p24 antigen assay with heat-denatured plasma. AIDS 1997; 11:F47-F52.Schüpbach J, Böni J. Sensitivity of heat-denatured p24 antigen in the diagnosis of pediatric HIV infection. J AIDS Hum Retrovirol 1998;18:399-400.Nadal D, Böni J, Kind C, Varnier OE, Steiner F, Tomasik Z, Schüpbach J. Prospective evaluation of amplification–boosted ELISA for heat-denatured p24 antigen for diagnosis and monitoring of paediatric HIV-1 infection. J Infect Dis 1999;180:1089-1095.Schüpbach J and Varnier OE. HIV-1 p24 antigen — a sensitive and precise, yet inexpensive alternative to PCR for viral DNA or RNA. International AIDS Society Newsletter Nr. 15, April 2000, 9-10.Schüpbach J, Tomasik Z, Nadal D, Flepp M, Ledergerber B, Opravil M, Böni J. Use of HIV-1 p24 as a sensitive, precise and inexpensive marker for infection, disease progression and treatment failure. Int. J. Antimicrob. Agents 2000; 16: 441-445.Ledergerber B, Flepp M, Böni J, Tomasik Z, Lüthy R and Schüpbach J. HIV-1 p24 concentration measured by boosted ELISA of heat-denatured plasma correlates with CD4+ decline, progression to AIDS and survival: Comparison with viral RNA. J Infect Dis 2000; 181:1280-1288.Schüpbach J, Böni J, Flepp M, Tomasik Z, Joller H, Opravil M. Antiretroviral treatment monitoring with an improved HIV-1 p24 antigen test: an inexpensive alternative to tests for viral RNA. J. Med. Virol 2001; 65:225-232.Schüpbach J. Measurement of HIV-1 p24 antigen by signal-amplification-boosted ELISA of heat-denatured plasma is a simple and inexpensive alternative to tests for viral RNA. AIDS Rev 2002;4(2):83-92.Sterling TR, Hoover DR, Astemborski J, Vlahov D, Bartlett JG, Schüpbach J. Prognostic value of heat-denatured HIV-1 p24 antigen and correlation with plasma HIV-1 viral load and CD4+ T-lymphocyte level in adults. J Infect. Dis 2002; 186:1181-1185.Schüpbach J, Böni J, Bisset LR, Tomasik Z, Fischer M, Günthard H, Ledergerber B, Opravil M for the Swiss HIV Cohort Study. HIV-1 p24 antigen is an independent correlate of CD4 T-cell change in patients on successful long-term antiretroviral therapy. J Acquir Imm Defic Syndr 2003; 33:292-299.García Ribas S, Ondoa P, Schüpbach J, van der Groen G, Fransen K. Performance of a quantitative human immunodeficiency virus type 1 p24 antigen assay on various HIV-1 subtypes for the follow-up of human immunodeficiency type 1 seropositive individuals. J. Virol. Methods 2003; 113: 29-34Schüpbach J. Viral RNA and p24 antigen as markers of HIV disease and antiretroviral treatment success. Int Arch Allergy Immunol 2003; 132:196-209.Schüpbach J, Günthard H, Joos B, Fischer M, Böni J, Tomasik Z, Yerly S, Perrin L, Battegay M, Furrer H, Vernazza P, Bernasconi E, Hirschel B, and the Swiss HIV Cohort Study. HIV-1 p24 may persist during long-term HAART, increases little during short treatment breaks, and its rebound after treatment stop correlates with the CD4+ loss. J Acquir Imm Defic Syndr 2005; 40:250-256.Jennings C, Fiscus SA, Crowe SM, Danilovic AD, Morack RJ, Scianna S, Cachafeiro A, Brambilla DJ, Schupbach J, Dunne A, Stevens W, Respess R, Varnier OE, Corrigan G, Gronowitz JS, Ussery MA, and Bremer JW. A Comparison of two HIV RNA surrogate assays for use in monitoring HIV-infected patients in resource-limited countries. J Clin Microbiol 2005; 43:5950-5956.Brinkhof MWG, Böni J, Steiner F, Tomasik Z, Nadal D, Schüpbach J and the Swiss
HIV Cohort Study (SHCS) and the Swiss HIV Mother + Child Cohort Study
(MoCHiV). Evaluation of p24-based antiretroviral treatment monitoring in
pediatric HIV-1 infection: prediction of the CD4+ T cell changes between
consecutive visits. J Acquir Immune Defic Syndr 2006; 41: 557-562.Knuchel MC, Tomasik Z, Speck RF, Lüthy R, and Schüpbach J. Ultrasensitive
quantitative HIV-1 p24 antigen assay adapted to dried plasma spots to improve
treatment monitoring in low-resource settings. J Clin Virol 2006; 36:64–67.Schüpbach J, Tomasik Z, Knuchel M, Opravil M, Günthard HF, Nadal D, Böni J and
the Swiss HIV Cohort Study (SHCS) and the Swiss HIV Mother + Child Cohort
Study (MoCHiV). Optimized virus disruption improves detection of HIV-1 p24 and
uncovers a p24 reactivity in patients with undetectable HIV-1 RNA under long-
term HAART. J Med Virol 2006; 78:1003–1010.Knuchel MC, Jullu B, Shah C, Tomasik Z, Böni J, Speck RF, Nadal D, Mshinda H, Stöckle MP, Tanner M and Schüpbach J. Adaptation of the Ultrasensitive HIV-1 p24 Antigen Assay to Dried Blood Spot Testing. J Acquir Imm Defic Syndr 2007; 44:247-253.Erikstrup C, Kallestrup P, Zinyama R, Gomo E, Lüneborg-Nielsen M, Jan Gerstoft, Ullum H, Schüpbach J, Katzenstein TL. p24 as a predictor of mortality in a cohort of HIV-1-infected adults in rural Africa. J Acquir Imm Defic Syndr 2008;48:345-349.Weitere Informationen
|Keywords / Suchbegriffe||HIV, AIDS, antigen test, PCR, diagnosis, antiretroviral treatment, patient monitoring, virus load, prognosis, drug resistance, resource-poor settings, North-South collaboration|
|Project leadership and contacts /
Projektleitung und Kontakte
|Other links to external web pages||http://onlinelibrary.wiley.com/doi/10.1002/jmv.20655/abstract;jsessionid=9B63F00D0F83B7B54886367F4979BBD9.d01t02|
|Funding source(s) /
|SNF (Personen- und Projektförderung), Other Public Sources (e.g. Federal or Cantonal Agencies), Foundation, Private Sector (e.g. Industry)
|In collaboration with /
In Zusammenarbeit mit
|Duration of Project / Projektdauer||Jan 1993 to Dec 2015|