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Window PeriodThe window period is the time after HIV infection during which a specific test (usually an antibody test) is negative. This is believed to be a few weeks for antibody tests and shorter or longer for genetic tests (PCR, Viral Load) depending on which research you believe. One problem is, in the absence of artificial infection tests (i.e. infecting a human being with pure virus so the date of infection is known) how could you know for sure what the date of infection was?Immune responses are activated, but neutralizing HIV antibodies do not occur before 4 months after primary infection and insufficient to eradicate infection. The discoveries of human papilloma viruses that cause cervical cancer and of human immunodeficiency virus. Nobel Prize Committee. 2008 Oct 6 http://nobelprize.org/nobel_prizes/medicine/laureates/2008/adv.pdf The [new] Genscreen Plus HIV AntigenAntibody is an EIA [Enzyme Immuno-Assay or ELISA] for the detection of HIV infection based on the detection (sandwich technique) of antibodies to HIV-1 and HIV-2, as well as the HIV-1 p24 antigen in human serum or plasma. These assays become valuable in diagnosing early HIV infection, reducing the window period by 45 days compared with third-generation assays
Using this assay in 18 infants with three consecutive negative HIV-DNA PCR we found that
10 were positive (age range 1920 months). Of the 10 infants positive by the fourth generation assay, nine were negative by our previous third-generation HIV assay (performed simultaneously). Repeat fourth-generation EIA testing was negative for nine infants within a few months, confirming waning levels of maternal antibody and not emerging infection. In one infant it was not possible to obtain a repeat sample but it shows no clinical evidence of HIV infection [although a positive HIV test with no symptoms is usually accepted as a genuine infection]. Nastouli E et al. False-positive HIV antibody results with ultrasensitive serological assays in uninfected infants born to mothers with HIV. AIDS. 2007 May 31;21(9):1222-1223. HIV EIAs have become increasingly more sensitive and specific since HIV testing began in the early 1980s. This has shortened the window period, or the time from exposure to seroconversion, from up to 12 weeks or more in the early days of diagnostic testing to the current window period of less than three weeks in most cases. The small disadvantage of such a highly sensitive test is that the test produces false positives, the number and type of which vary with the assay used and the HIV prevalence in the tested population. Fearon M. The laboratory diagnosis of HIV infections. Can J Infect Dis Med Microbiol. 2005 Jan;16(1):26-30. Although unproven, the presumed mechanism for HIV PEP comes from animal and human work suggesting that shortly after an exposure to HIV, a window period exists during which the viral load is small enough to be controlled by the body's immune system. Merchant RC, Keshavarz R. Human Immunodeficiency Virus Postexposure Prophylaxis for adolescents and children. Pediatrics. 2001 Aug;108(2):e38. http://www.pediatrics.org/cgi/reprint/108/2/e38.pdf In June 1997, whole blood was collected from a repeat blood donor at the Singapore Blood Transfusion Service, Singapore, after the donor denied having any HIV-related risk factors. At that time, serum from the donor tested negative for both HIV antibodies and p24 antigen. When returning in October 1997, the donor was found to be HIV antibody positive. Two recipients of platelets and red blood cells derived from the June 1997 donation also tested positive for HIV
The 2 commercial quantitative RNA assays failed to detect HIV RNA during the window period [the time after infection in which antibodies are already believed not to be present] Ling AE et al. Failure of routine HIV-1 tests in a case involving transmission with preseroconversion blood components during the infectious window period. JAMA. 2000 Jul 12;284(2):210-4. In two-thirds (64) of the 94 cases [of documented HIV infection], the time of the first positive test for antibodies to HIV was reported. Seroconversion within 6 months of exposure was documented in 57 case patients (89%); of these, 42 had been tested and found to be seropositive by 3 months following exposure. Of the 15 first found to seropositive at 6 months post-exposure, only two (cases 9 and 31) had been tested at 104 days and 42 days post-exposure, respectively. In eight cases, antibodies to HIV were first detected at more than 6 months post-exposure; one (case 18) had been tested at 3 but not 6 months following exposure, and four (cases 47, 52, 61, and 66) had a documented negative test HIV antibodies at 6 months post-exposure. One (case 66) was retested on presentation with an AIDS-defining illness months after exposure
An acute retroviral illness occurred in 42 case patients
In 33 (79%) of these, the onset of symptoms occurred within 6 weeks of exposure. Ippolito G et al. Occupational human immunodeficiency virus infection in health care workers: worldwide cases through September 1997. Clin Infect Dis. 1999 Feb;28(2):365-83. 225 cultures of peripheral-blood lymphocytes from 133 seronegative men were performed, and HIV-1 was isolated [actually, detected indirectly using non-specific markers] in cultures from 31 men (23%). Of these men, four have seroconverted after being seronegative for 11 to 17 months after the initial isolation of the virus. The virus was not always isolated at every visit after the first successful isolation Imagawa DT et al. Human immunodeficiency virus type I infection in homosexual men who remain seronegative for prolonged periods. N Engl J Med. 1989 Jun 1;320(22):1458-62. The recently recognized cases of virus transmission by blood transfusion are due to donors being missed by current antibody screening tests during the window of seroconversion. There is a period of about 4 to 8 weeks in which newly HIV-infected persons are capable of transmitting HIV, but have not yet developed antibodies. Blattner W, Gallo RC, Temin HM. HIV Causes AIDS (with response by Peter Duesberg). Science. 1988 Jul 29;241:515,517. recent research has indicated that infection may precede seroconversion by as much as several years in some individuals Detels R et al. Patterns of CD4+ cell changes after HIV-1 infection indicate the existence of a codeterminant of AIDS. J Acquir Immune Defic Syndr. 1988;1(4):390-5. A donor who became HIV+ was investigated, and one person who had received his blood before his seroconversion (among 26 other units) was found to be positive by ELISA and WB 4 months after transfusion van der Poel CL et al. Transmission of HIV by transfusion of ELISA-negative blood. Vox Sang. 1988;54(4):247. Free HIV antigen and/or low-titre antibodies to recombinant structural or non-structural proteins were seen 6-14 months before seroconversion in all 9 subjects who seroconverted [so, isnt the window period 6-14 months then?] Ranki A et al. Long latency precedes overt seroconversion in sexually transmitted human-immunodeficiency-virus infection. Lancet. 1987 Sep 12;2:589-93. | ||||||||||||||
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