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HIV檢測

维基百科,自由的百科全书

这是本页的一个历史版本,由Yst1107留言 | 贡献2007年12月29日 (六) 12:18编辑。这可能和当前版本存在着巨大的差异。

HIV(人類免疫缺陷病毒)檢測用来診斷治療追蹤感染人類免疫缺陷病毒的人。在美國檢測工作由美國食品藥物管理局主管,在台灣則由衛生署主管。

HIV檢測是偵測血漿血清唾液乾血點尿液之中的抗體抗原、或是RNA

名詞解釋

空窗期: 從被HIV感染之後到可以檢測出病毒所需之時間。使用抗體檢測之方式平均之空窗期為22天。使用抗原檢測方法則可縮減空窗期至16天,而使用核酸檢測法(NAT)則可使空窗期減至12天。[1]

而一個醫學檢測的效果通常使用以下術語描述︰

  • 靈敏度: 如感染HIV時,檢驗結果為陽性的百分比(真陽性/陽性)
  • 特異度: 如未感染HIV時,檢驗結果為陰性的百分比(真陰性/陰性)

所有的診斷檢查都有侷限性,有時候,它們可能會產生錯誤或有疑問的結果。

  • 假陽性: 當一個人沒有感染HIV時,但檢驗結果卻顯示為陽性。
  • 假陰性: 當一個人感染HIV時,但檢驗結果卻顯示為陰性。

非特異性反應高伽瑪球蛋白血症或存在針對其他病原體而類似HIV病毒抗原的抗體可能產生假陽性結果。自體免疫性疾病,如系統性紅斑狼瘡 ,也可能造成假陽性的結果。


原則

用在捐贈血液或細胞產品篩檢之時

被選為篩選捐贈血液或組織的HIV測試必須對於其中不存在HIV提供足夠高的信心(也就是要能提供高靈敏度)。在西方國家,血庫會一起併用抗體抗原核酸之測試。世界衛生組織預估在2000年時,全世界因不當的血液篩選造成了一百萬新的HIV感染病例。

美國,大部份的捐贈血液使用酵素免疫分析法(ELISA)和核酸測試來篩選HIV-1和HIV-2的存在。這一些檢驗也和一些細心的捐贈者篩選一併進行。在2001年時,在美國因每次輸血感染HIV的風險約為2千5百萬分之一。[2]

用在HIV感染診斷之時

用在診斷特定某一人是否感染HIV時之檢測會同時需要很高的敏感度特異度。在美國,為達到此一目標,HIV檢測使用了一種演算法來結合兩種HIV抗體測試。如果在一開始使用一種以ELISA為基礎的檢測方法發現到了HIV抗體,再來使用西方墨點法做第二次檢測以檢驗和該抗體結合之抗原分子量大小。此種結合方法可以提供較高的準確度(詳下文)。

關於人權

聯合國愛滋病規劃署(UNAIDS)及世界衛生組織對於HIV篩選的政策聲明為,對於進行HIV檢測的人,必須立足於一個人權的原則下以尊重醫學倫理[3]跟據這些原則,進行HIV檢測的人必須要:

  • 保密
  • 伴隨著諮詢(對於那些試驗陽性的個案)
  • 經過知情同意才進行測試

抗體測試

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HIV antibody tests are specifically designed for routine diagnostic testing of adults; these tests are inexpensive and extremely accurate.

空窗期

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Antibody tests may give false negative results during the window period, an interval of three weeks to six months between the time of HIV infection and the production of measurable antibodies to HIV (so-called seroconversion). Most people develop detectable antibodies approximately 30 days after infection, although some seroconvert later. The vast majority of people (99%) have detectable antibodies by three months after HIV infection; a six-month window is extremely rare with modern antibody testing.[4] During the window period, an infected person can transmit HIV to others although their HIV infection may not be detectable with an antibody test. Antiretroviral therapy during the window period can delay the formation of antibodies and extend the window period beyond 12 months.[5] Antibody tests may also yield false negative results in patients with X-linked agammaglobulinemia; other diagnostic tests should be used in such patients.

Three instances of delayed HIV seroconversion occurring in Health-care workers have been reported;[6] in these instances, the Health-care workers[7] tested negative for HIV antibodies greater than 6 months postexposure but were seropositive within 12 months after the exposure.[8] DNA sequencing confirmed the source of infection in one instance. Two of the delayed seroconversions were associated with simultaneous exposure to hepatitis C virus (HCV). In one case, co-infection was associated with a rapidly fatal HCV disease course; however, it is not known whether HCV directly influences the risk for or course of HIV infection or is a marker for other exposure-related factors.

酵素免疫分析法(ELISA)

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The ELISA test, or the enzyme immunoassay (EIA), was the first screening test commonly employed for HIV. It has a high sensitivity.

In an ELISA test, a person's serum is diluted 400-fold and applied to a plate to which HIV antigens have been attached. If antibodies to HIV are present in the serum, they may bind to these HIV antigens. The plate is then washed to remove all other components of the serum. A specially prepared "secondary antibody" — an antibody that binds to human antibodies — is then applied to the plate, followed by another wash. This secondary antibody is chemically linked in advance to an enzyme. Thus the plate will contain enzyme in proportion to the amount of secondary antibody bound to the plate. A substrate for the enzyme is applied, and catalysis by the enzyme leads to a change in color or fluorescence. ELISA results are reported as a number; the most controversial aspect of this test is determining the "cut-off" point between a positive and negative result.

西方墨點法(Western blot)

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In the Western blot procedure, cells that may be HIV-infected are opened and the proteins within are placed into a slab of gel, to which an electrical current is applied. Different proteins will move with different velocities in this field, depending on their size, while their electrical charge is leveled by a surfactant called sodium lauryl sulfate. Once the proteins are well-separated, they are transferred to a membrane and the procedure continues similar to an ELISA: the person's diluted serum is applied to the membrane and antibodies in the serum may attach to some of the HIV proteins. Antibodies which do not attach are washed away, and enzyme-linked antibodies with the capability to attach to the person's antibodies determine to which HIV proteins the person has antibodies.

There are no universal criteria for interpreting the Western blot test: the number of viral bands which must be present may vary. If no viral bands are detected, the result is negative. If at least one viral band for each of the GAG, POL, and ENV gene-product groups are present, the result is positive. The three-gene-product approach to Western blot interpretation has not been adopted for public health or clinical practice. Tests in which less than the required number of viral bands are detected are reported as indeterminate: a person who has an indeterminate result should be retested, as later tests may be more conclusive. Almost all HIV-infected persons with indeterminate Western-Blot results will develop a positive result when tested in one month; persistently indeterminate results over a period of six months suggests the results are not due to HIV infection. In a generally healthy low-risk population, indeterminate results on Western blot occur on the order of 1 in 5,000 patients.[9]

快速檢驗或重點照護檢驗

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A woman demonstrates the use of the OraQuick rapid HIV test

Rapid Antibody Tests are qualitative immunoassays intended for use as a point-of-care test to aid in the diagnosis of HIV infection. These tests should be used in conjunction with the clinical status, history, and risk factors of the person being tested. The specificity of Rapid Antibody Tests in low-risk populations has not been evaluated. These tests should be used in appropriate multi-test algorithms designed for statistical validation of rapid HIV test results.

If no antibodies to HIV are detected, this does not mean the person has not been infected with HIV. It may take several months after HIV infection for the antibody response to reach detectable levels, during which time rapid testing for antibodies to HIV will not be indicative of true infection status. A comprehensive risk history and clinical judgement should be considered before concluding that an individual is not infected with HIV.

OraQuick is an antibody test that provides results in 20 minutes. The blood, plasma or oral fluid is mixed in a vial with developing solution, and the results are read from a sticklike testing device.

Orasure is an HIV test which uses mucosal transudate from the tissues of cheeks and gums. It is an antibody test which first employs ELISA, then Western Blot.

There is also a urine test; it employs both the ELISA and the Western Blot method.

Home Access Express HIV-1 Test is a FDA-approved home test: the patient collects a drop of blood and mails the sample to a laboratory; results and counseling are obtained over the phone.

There have been a number of cases of fraudulent tests being sold via mail order or the Internet to the general public. In 1997, a California man was indicted on mail fraud and wire charges for selling supposed home test kits. In 2004, the US Federal Trade Commission asked Federal Express and US Customs to confiscate shipments of the Discreet home HIV test kits, produced by Gregory Stephen Wong of Vancouver, BC. In February 2005, the US FDA issued a warning against using the rapid HIV test kits and other home use kits marketed by Globus Media of Montreal Canada.

解析式抗體檢驗(Interpreting antibody tests)

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ELISA testing alone cannot be used to diagnose HIV, even if the test suggests a high probability that antibody to HIV-1 is present. In the United States, such ELISA results are not reported as "positive" unless confirmed by a Western Blot.

The ELISA antibody tests were developed to provide a high level of confidence that donated blood was NOT infected with HIV. It is therefore not possible to conclude that blood rejected for transfusion because of a positive ELISA antibody test is in fact infected with HIV. Sometimes, retesting the donor in several months will produce a negative ELISA antibody test. This is why a confirmatory Western Blot is always used before reporting a "positive" HIV test result.

False positive results due to factors unrelated to exposure to HIV are found more often with the ELISA test than with the Western Blot. False positives can be caused by antibodies to viruses other than HIV, antibodies produced by pregnancy, and other medical conditions such as recent acute illnesses, influenza vaccinations and allergies[10]. A false positive result does not indicate a condition of significant risk to health. When the ELISA test is combined with Western Blot, the rate of false positives is extremely low, and diagnostic accuracy is very high (see below).

HIV檢驗的精確度

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The evidence regarding the risks and benefits of HIV screening was reviewed in July 2005 by the U.S. Preventive Services Task Force.[11] The authors concluded that:

...the use of repeatedly reactive enzyme immunoassay followed by confirmatory Western blot or immunofluorescent assay remains the standard method for diagnosing HIV-1 infection. A large study of HIV testing in 752 U.S. laboratories reported a sensitivity of 99.7% and specificity of 98.5% for enzyme immunoassay, and studies in U.S. blood donors reported specificities of 99.8% and greater than 99.99%. With confirmatory Western blot, the chance of a false-positive identification in a low-prevalence setting is about 1 in 250 000 (95% CI, 1 in 173 000 to 1 in 379 000).

Other studies have confirmed the accuracy of current methods of HIV testing in the United States, reporting false-positive rates of 0.0004% to 0.0007% and false-negative rates of 0.003% in the general population.[12][13][14][15][16][17][18][19]

抗體測試

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The p24 antigen test detects the presence of the p24 protein of HIV (also known as CA), a major core protein of the virus. Monoclonal antibodies specific to the p24 protein are mixed with the person's blood. Any p24 protein in the person's blood will stick to the monoclonal antibody and enzyme-linked antibody to the monoclonal antibodies to p24 causes a color change if p24 was present in the sample.

This test is no longer used routinely in the US[2] or the EU [3] to screen blood donations since the objective was to reduce the risk of false negatives in the window period. Nucleic acid testing (NAT) is more effective for this purpose, and p24 antigen testing is no longer indicated if a NAT test is performed. The p24 antigen test is not useful for general diagnostics, as it has very low sensitivity and only works during a certain time period after infection before the body produces antibodies to the p24 protein.

核酸測試(NAT)

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Nucleic-acid-based tests amplify and detect a 142-base target sequence located in a highly conserved region of the HIV gag gene [來源請求]. Since 2001, donated blood in the United States has been screened with nucleic-acid-based tests, shortening the window period between infection and detectability of disease to about 12 days. Since these tests are relatively expensive, the blood is screened by first pooling some 10-20 samples and testing these together; if the pool tests positive, each sample is retested individually. A different version of this test is intended for use in conjunction with clinical presentation and other laboratory markers of disease progress for the management of HIV-1-infected patients.

In the RT-PCR test, viral RNA is extracted from the patient's plasma and is treated with reverse transcriptase so that the RNA of the virus is transcribed into DNA. The polymerase chain reaction (PCR) is then applied, using two primers thought to be unique to the virus's genome. After the PCR amplification process is complete, the resulting amplified segments bind to specific oligonucleotides bound to the vessel wall and are then made visible with a probe bound to an enzyme. The amount of virus in the sample can be quantified with sufficient accuracy to detect three-fold changes.

In the Quantiplex bDNA or branched DNA test, plasma is centrifugated to concentrate the virus, which is then opened to release its RNA. Special oligonucleotides are added which bind to viral RNA and to certain oligonucleotides bound to the wall of the vessel. In this way, viral RNA is fastened to the wall. Then new oligonucleotides are added which bind at several locations to this RNA; and other oligonucelotides which bind at several locations to those oligonucleotides. This is done to amplify the signal. Finally, oligonucleotides that bind to the last set of oligonucleotides and that are bound to an enzyme are added; the enzyme action causes a color reaction which allows quantification of the viral RNA in the original sample. Monitoring the effects of antiretroviral therapy by serial measurements of plasma HIV-1 RNA with this test has been validated for patients with viral loads greater than 25,000 copies per milliliter.[20]

其它HIV/AIDS之檢驗

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The CD4 T-cell count is not an HIV test, but rather a procedure where the number of CD4 T-cells in the blood is determined.

A CD4 count does not check for the presence of HIV. It is used to monitor immune system function in HIV-positive people. Declining CD4 T-cell counts are considered to be a marker of progression of HIV infection. In HIV-positive people, AIDS is officially diagnosed when the count drops below 200 cells/μL or when certain opportunistic infections occur. This use of a CD4 count as an AIDS criterion was introduced in 1992; the value of 200 was chosen because it corresponded with a greatly increased likelihood of opportunistic infection. Lower CD4 counts in people with AIDS are indicators that prophylaxis against certain types of opportunistic infections should be instituted.

Low CD4 T-cell counts are associated with a variety of conditions, including many viral infections, bacterial infections, parasitic infections, sepsis, tuberculosis, coccidioidomycosis, burns, trauma, intravenous injections of foreign proteins, malnutrition, over-exercising, pregnancy, normal daily variation, psychological stress, and social isolation.[來源請求]

This test is also used occasionally to estimate immune system function for people whose CD4 T cells are impaired for reasons other than HIV infection, which include several blood diseases, several genetic disorders, and the side effects of many chemotherapy drugs.

Generally speaking, the lower the number of T cells, the lower the immune system's function will be. Normal CD4 counts are between 500 and 1500 CD4+ T cells/microliter, and the counts may fluctuate in healthy people depending on recent infection status, nutrition, exercise and other factors. Women tend to have somewhat lower counts than men.

Duo/combined tests are also available which combine antigen and antibody testing, thereby making earlier detection possible.[21]

HIV檢驗的爭議

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HIV tests have been criticized by a number of AIDS dissidents (people who reject the scientific consensus that HIV causes AIDS), including the Perth Group of scientists (led by Eleni Papadopulos-Eleopulos) who question the very existence of HIV. Their arguments rest on issues of specificity, standardisation, reproducibility, and validation.[22]

According to scientific consensus, the accuracy of serologic testing has been verified by isolation and culture of HIV and by detection of HIV RNA by PCR, which are widely accepted "gold standards" in microbiology.[23][24] While the AIDS dissidents focus on individual components of HIV testing, it is generally believed that the combination of ELISA and Western Blot used for the diagnosis of HIV is remarkably accurate, with very low false-positive and -negative rates as described above. The vast majority of scientists believe that the views of AIDS dissidents are based on highly selective analysis of mostly outdated scientific papers; there is broad scientific consensus that HIV is the cause of AIDS.[25][26][27]

參考資料

(皆為英文)

  1. ^ http://www.fda.gov/bbs/topics/ANSWERS/2001/ANS01103.html
  2. ^ Adverse reactions associated with blood transfusion. From the Puget Sound Blood Center. Accessed 5 Oct 2006.
  3. ^ UNAIDS/WHO policy statement on HIV Testing (PDF), accessed 5 Oct 2006.
  4. ^ Update on the HIV Antibody Test Window Period, from the Seattle and King County Public Health Department. Accessed 21 Feb 2007.
  5. ^ C B Hare, B L Pappalardo, M P Busch, B Phelps, S S Alexander, C Ramstead, J A Levy, F M Hecht. Negative HIV antibody test results among individuals treated with antiretroviral therapy (ART) during acute/early infection. The XV International AIDS Conference: Abstract no. MoPeB3107. 2004. 
  6. ^ Ridzon R, Gallagher K, Ciesielski C, et al. Simultaneous transmission of human immunodeficiency virus and hepatitis C virus from a needle-stick injury. N Engl J Med 1997;336:919-22.
  7. ^ HIV Seroconversion in HEALTH-CARE WORKERS
  8. ^ J.L. Gerberding, San Francisco General Hospital, unpublished data, May 1997
  9. ^ Bartlett, JG. Serologic tests for the diagnosis of HIV infection, in UpToDate. Accessed 5 Oct 2006.
  10. ^ Simonsen et al: "Multiple False Reactions in Viral Antibody Screening Assays after Influenza Vaccination", American Journal of Epidemiology Vol. 141, No. 11: 1089-1096
  11. ^ "Screening for HIV: A Review of the Evidence for the U.S. Preventive Services Task Force", Annals of Internal Medicine, Chou et. al, Volume 143 Issue 1, pp. 55-73. [1]
  12. ^ Kleinman S, Busch M, Hall L, Thomson R, Glynn S, Gallahan D, Ownby H, Williams A. False-positive HIV-1 test results in a low-risk screening setting of voluntary blood donation. Retrovirus Epidemiology Donor Study.. JAMA. 1998, 280 (12): 1080–5. PMID 9757856. 
  13. ^ Burke D, Brundage J, Redfield R, Damato J, Schable C, Putman P, Visintine R, Kim H. Measurement of the false positive rate in a screening program for human immunodeficiency virus infections.. N Engl J Med. 1988, 319 (15): 961–4. PMID 3419477. 
  14. ^ MacDonald K, Jackson J, Bowman R, Polesky H, Rhame F, Balfour H, Osterholm M. Performance characteristics of serologic tests for human immunodeficiency virus type 1 (HIV-1) antibody among Minnesota blood donors. Public health and clinical implications.. Ann Intern Med. 1989, 110 (8): 617–21. PMID 2648922. 
  15. ^ Busch M, Eble B, Khayam-Bashi H, Heilbron D, Murphy E, Kwok S, Sninsky J, Perkins H, Vyas G. Evaluation of screened blood donations for human immunodeficiency virus type 1 infection by culture and DNA amplification of pooled cells.. N Engl J Med. 1991, 325 (1): 1–5. PMID 2046708. 
  16. ^ Van de Perre P, Simonon A, Msellati P, Hitimana D, Vaira D, Bazubagira A, Van Goethem C, Stevens A, Karita E, Sondag-Thull D. Postnatal transmission of human immunodeficiency virus type 1 from mother to infant. A prospective cohort study in Kigali, Rwanda.. N Engl J Med. 1991, 325 (9): 593–8. PMID 1812850. 
  17. ^ Update: serologic testing for HIV-1 antibody--United States, 1988 and 1989. MMWR Morb Mortal Wkly Rep 1990; 39:380.
  18. ^ Urnovitz H, Sturge J, Gottfried T. Increased sensitivity of HIV-1 antibody detection.. Nat Med. 1997, 3 (11): 1258. PMID 9359701. 
  19. ^ Farzadegan H, Vlahov D, Solomon L, Muñoz A, Astemborski J, Taylor E, Burnley A, Nelson K. Detection of human immunodeficiency virus type 1 infection by polymerase chain reaction in a cohort of seronegative intravenous drug users.. J Infect Dis. 1993, 168 (2): 327–31. PMID 8335969. 
  20. ^ FDA summary of branched DNA test, accessed 5 Oct 2006.
  21. ^ http://hivinsite.ucsf.edu/InSite?page=kb-02-02-01-a
  22. ^ Papadopulos-Eleopulos E, Turner V, Papadimitriou J. Is a positive western blot proof of HIV infection?. Biotechnology (N Y). 1993, 11 (6): 696–707. PMID 7763673. 
  23. ^ Busch M, Eble B, Khayam-Bashi H, Heilbron D, Murphy E, Kwok S, Sninsky J, Perkins H, Vyas G. Evaluation of screened blood donations for human immunodeficiency virus type 1 infection by culture and DNA amplification of pooled cells.. N Engl J Med. 1991, 325 (1): 1–5. PMID 2046708. 
  24. ^ MacDonald K, Jackson J, Bowman R, Polesky H, Rhame F, Balfour H, Osterholm M. Performance characteristics of serologic tests for human immunodeficiency virus type 1 (HIV-1) antibody among Minnesota blood donors. Public health and clinical implications.. Ann Intern Med. 1989, 110 (8): 617–21. PMID 2648922. 
  25. ^ AIDSTruth.org, site focused on examining AIDS dissident claims. Accessed 5 Oct 2006.
  26. ^ National Institutes of Health fact sheet on the connection between HIV and AIDS. Accessed 5 Oct 2006.
  27. ^ Series of articles from Science magazine, debunking the claims of AIDS dissidents. Accessed 5 Oct 2006.

外部連結

(皆為英文)