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. 1997 Mar;35(3):631–635. doi: 10.1128/jcm.35.3.631-635.1997

Deterioration of detectable human immunodeficiency virus serum p24 antigen in samples stored for batch testing.

J L Lathey 1, I C Marschner 1, B Kabat 1, S A Spector 1
PMCID: PMC229640  PMID: 9041402

Abstract

Virologic measurements are becoming important surrogate markers for therapeutic efficacy in clinical trials with human immunodeficiency virus (HIV)-infected subjects. One such marker which is inexpensive and easily evaluated is the HIV p-24 antigen. To determine the storage stability of p24 antigen assayed by enzyme-linked immunosorbent assay of serum collected during clinical trials, a retrospective analysis was performed. The p24 antigen results were available from four Adult or Pediatric AIDS Clinical Trials Group protocols: studies 047, 050, 128, and 213. Paired samples (n = 930) which were assayed by ELISA for p24 antigen both in real time and in batch were analyzed for agreement. Batch and real-time values were correlated; however, there was a lack of agreement which increased with prolonged storage time of batched samples and greater p24 antigen levels. The p24 antigen values were significantly lower in the batched samples, which had a maximum storage time of 1,548 days. The degradation rate of p24 antigen per year was 0.052 log10 for samples with less than 30 pg/ml, 0.197 log10 for those with 30 to 100 pg/ml, and 0.245 log10 for those with > 100 pg/ml. Due to degradation over time, use of p24 antigen values from batch assays with long-term storage could bias study results toward a lack of treatment effect. On the basis of these results we make the following recommendations. (i) Samples should be assayed either in real time by laboratories undergoing quality assurance or in batch with short-term storage (less than 1 year). (ii) When real-time assays are to be performed, the serum samples should not be stored at 4 degrees C, but should be frozen immediately after processing and stored frozen until tested.

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Selected References

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  1. Aboulker J. P., Swart A. M. Preliminary analysis of the Concorde trial. Concorde Coordinating Committee. Lancet. 1993 Apr 3;341(8849):889–890. doi: 10.1016/0140-6736(93)93096-j. [DOI] [PubMed] [Google Scholar]
  2. Bozzette S. A., Richman D. D. Salvage therapy for zidovudine-intolerant HIV-infected patients with alternating and intermittent regimens of zidovudine and dideoxycytidine. Am J Med. 1990 May 21;88(5B):24S–26S. doi: 10.1016/0002-9343(90)90418-d. [DOI] [PubMed] [Google Scholar]
  3. Brady M. T., McGrath N., Brouwers P., Gelber R., Fowler M. G., Yogev R., Hutton N., Bryson Y. J., Mitchell C. D., Fikrig S. Randomized study of the tolerance and efficacy of high- versus low-dose zidovudine in human immunodeficiency virus-infected children with mild to moderate symptoms (AIDS Clinical Trials Group 128). Pediatric AIDS Clinical Trials Group. J Infect Dis. 1996 May;173(5):1097–1106. doi: 10.1093/infdis/173.5.1097. [DOI] [PubMed] [Google Scholar]
  4. Cheeseman S. H., Havlir D., McLaughlin M. M., Greenough T. C., Sullivan J. L., Hall D., Hattox S. E., Spector S. A., Stein D. S., Myers M. Phase I/II evaluation of nevirapine alone and in combination with zidovudine for infection with human immunodeficiency virus. J Acquir Immune Defic Syndr Hum Retrovirol. 1995 Feb 1;8(2):141–151. [PubMed] [Google Scholar]
  5. DeGruttola V., Beckett L. A., Coombs R. W., Arduino J. M., Balfour H. H., Jr, Rasheed S., Hollinger F. B., Fischl M. A., Volberding P. Serum p24 antigen level as an intermediate end point in clinical trials of zidovudine in people infected with human immunodeficiency virus type 1. Aids Clinical Trials Group Virology Laboratories. J Infect Dis. 1994 Apr;169(4):713–721. doi: 10.1093/infdis/169.4.713. [DOI] [PubMed] [Google Scholar]
  6. Eron J. J., Benoit S. L., Jemsek J., MacArthur R. D., Santana J., Quinn J. B., Kuritzkes D. R., Fallon M. A., Rubin M. Treatment with lamivudine, zidovudine, or both in HIV-positive patients with 200 to 500 CD4+ cells per cubic millimeter. North American HIV Working Party. N Engl J Med. 1995 Dec 21;333(25):1662–1669. doi: 10.1056/NEJM199512213332502. [DOI] [PubMed] [Google Scholar]
  7. Fiscus S. A., DeGruttola V., Gupta P., Katzenstein D. A., Meyer W. A., 3rd, LoFaro M. L., Katzman M., Ragni M. V., Reichelderfer P. S., Coombs R. W. Human immunodeficiency virus type 1 quantitative cell microculture as a measure of antiviral efficacy in a multicenter clinical trial. J Infect Dis. 1995 Feb;171(2):305–311. doi: 10.1093/infdis/171.2.305. [DOI] [PubMed] [Google Scholar]
  8. Griffith B. P., Brett-Smith H., Kim G., Mellors J. W., Chacko T. M., Garner R. B., Cheng Y. C., Alcabes P., Friedland G. Effect of stavudine on human immunodeficiency virus type 1 virus load as measured by quantitative mononuclear cell culture, plasma RNA, and immune complex-dissociated antigenemia. J Infect Dis. 1996 May;173(5):1252–1255. doi: 10.1093/infdis/173.5.1252. [DOI] [PubMed] [Google Scholar]
  9. Griffith B. P., Garner R. B., Chacko T. M. Stability of free and complexed human immunodeficiency virus type 1 antigen at 4 degrees C and at room temperature. J Clin Microbiol. 1995 May;33(5):1348–1350. doi: 10.1128/jcm.33.5.1348-1350.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Hammer S., Crumpacker C., D'Aquila R., Jackson B., Lathey J., Livnat D., Reichelderfer P. Use of virologic assays for detection of human immunodeficiency virus in clinical trials: recommendations of the AIDS Clinical Trials Group Virology Committee. J Clin Microbiol. 1993 Oct;31(10):2557–2564. doi: 10.1128/jcm.31.10.2557-2564.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Haubrich R. H., Flexner C., Lederman M. M., Hirsch M., Pettinelli C. P., Ginsberg R., Lietman P., Hamzeh F. M., Spector S. A., Richman D. D. A randomized trial of the activity and safety of Ro 24-7429 (Tat antagonist) versus nucleoside for human immunodeficiency virus infection. The AIDS Clinical Trials Group 213 Team. J Infect Dis. 1995 Nov;172(5):1246–1252. doi: 10.1093/infdis/172.5.1246. [DOI] [PubMed] [Google Scholar]
  12. Kappes J. C., Saag M. S., Shaw G. M., Hahn B. H., Chopra P., Chen S., Emini E. A., McFarland R., Yang L. C., Piatak M., Jr Assessment of antiretroviral therapy by plasma viral load testing: standard and ICD HIV-1 p24 antigen and viral RNA (QC-PCR) assays compared. J Acquir Immune Defic Syndr Hum Retrovirol. 1995 Oct 1;10(2):139–149. doi: 10.1097/00042560-199510020-00005. [DOI] [PubMed] [Google Scholar]
  13. Shepp D. H., Ashraf A. Effect of didanosine on human immunodeficiency virus viremia and antigenemia in patients with advanced disease: correlation with clinical response. J Infect Dis. 1993 Jan;167(1):30–35. doi: 10.1093/infdis/167.1.30. [DOI] [PubMed] [Google Scholar]
  14. Skowron G., Bozzette S. A., Lim L., Pettinelli C. B., Schaumburg H. H., Arezzo J., Fischl M. A., Powderly W. G., Gocke D. J., Richman D. D. Alternating and intermittent regimens of zidovudine and dideoxycytidine in patients with AIDS or AIDS-related complex. Ann Intern Med. 1993 Mar 1;118(5):321–330. doi: 10.7326/0003-4819-118-5-199303010-00001. [DOI] [PubMed] [Google Scholar]
  15. Spector S. A., Kennedy C., McCutchan J. A., Bozzette S. A., Straube R. G., Connor J. D., Richman D. D. The antiviral effect of zidovudine and ribavirin in clinical trials and the use of p24 antigen levels as a virologic marker. J Infect Dis. 1989 May;159(5):822–828. doi: 10.1093/infdis/159.5.822. [DOI] [PubMed] [Google Scholar]

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