Window periods

  • The window period is the time during which markers of infection are not detectable.
  • The length of the window period varies between individuals; UK guidelines state that for a fourth-generation test the window period is one month.
  • Testing during this period can result in false negative results.
  • People seeking testing may be confused or uncertain about the significance and length of window periods.

The window period refers to the time after infection and before seroconversion, during which markers of infection (HIV-specific antigen and antibodies) are still absent or too scarce to be detectable. Standard screening tests cannot reliably detect HIV infection until after the window period has passed.

Testing guidelines therefore recommend that a person who may have been recently infected should have a repeat test some weeks or months after the possible date of infection. But as there is a natural variation in the time it takes different individuals to produce detectable antigen and antibodies, definitive statements about the length of window periods are difficult to make.

Older recommendations were to defer testing until as much as three months after exposure.1

However, the effective window period has grown shorter with more sensitive, newer-generation assays. Current UK testing guidelines2,3 state that the time between infection and testing positive is typically one month. Many sources agree that, in many cases, the effective window period is probably shorter still: as little as one to three weeks.

However, messages around window periods may not always reflect these newer realities, and may not be consistent or clearly communicated. Some experts have expressed concerns that people may unnecessarily defer or avoid testing due to concerns or confusion about the window period.4,5

(The window period also depends on the type of assay used, which may also add some confusion: the figures stated here refer to the fourth-generation, antibody/antigen assays in standard use, while community-based, point-of-care tests used outside the medical clinic setting still have a suggested window period of twelve weeks.)

While testing during the window period should not necessarily be discouraged, it should be made clear that a negative result is not necessarily reliable (see False negatives), and that the person should return to the clinic to be retested.6 7 8

The British Association for Sexual Health and HIV issued a statement on window periods in 2010, noting that fourth-generation tests will detect the great majority of individuals who have been infected with HIV four weeks after exposure.

Moreover:

“Patients attending for HIV testing who identify a specific risk occurring more than 4 weeks previously, should not be made to wait 3 months (12 weeks) before HIV testing. They should be offered a 4th generation laboratory HIV test and advised that a negative result at 4 weeks post exposure is very reassuring / highly likely to exclude HIV infection. An additional HIV test should be offered to all persons at 3 months (12 weeks) to definitively exclude HIV infection. Patients at lower risk may opt to wait until 3 months to avoid the need for HIV testing twice.”3

Calculating window periods

Precise figures for the duration of the window period are difficult to come by, for a number of reasons:

  • There are individual variations in its duration.
  • People infrequently present to healthcare and have multiple plasma samples taken during this period, making this a difficult topic to investigate.
  • A single, precise date of exposure is rarely known.

To be calculated accurately, researchers would have to know the precise date that a person was exposed to HIV, and then have multiple plasma samples to test with different assays (for RNA, antigen or antibodies). From these results, it would be possible to give an average number of days during which tests were not able to detect the infection.

It is more common to be able to identify the first date on which HIV RNA was detectable, and then to calculate the number of days before which other assays are reactive. It is therefore possible to say HIV RNA becomes detectable approximately eleven days before antibodies (or that use of an HIV RNA test reduces the window period by eleven days). It is more challenging to say how many days after exposure HIV RNA is detectable, or what the total length of the window period is.

One way of calculating window periods9 therefore uses the first detection of HIV RNA as ‘day zero’:

  • First detection of p24 approximately five days later (typical range three to eight days).
  • First detection of antibodies approximately ten days after detection of RNA (typical range seven to thirteen days).

Nonetheless, there is also a gap between exposure and the first detection of HIV RNA. This is sometimes referred to as the eclipse phase, and refers to the time during which there is viral replication principally at the site of infection, before widespread dissemination of virus in the body (as observed in animal models). This time period has been thought by some to vary between four and eleven days,10,11 or by others to be between one and two weeks, but occasionally longer.12 13

Based on the assumption that HIV RNA is first detected approximately ten days after exposure, researchers have estimated11 window periods to be as follows.

  • First detection of HIV RNA: approximately ten days after exposure (typical range 7 to 21 days).
  • First detection of p24: approximately 17 days after exposure (typical range 13 to 28 days).
  • First detection of antibodies: approximately 22 days after exposure (typical range 18 to 34 days).

However, these are averages, and if the period between exposure and detectable viraemia is as variable as some authors suggest, these periods will occasionally be several weeks longer.

Moreover, the information we have is based on studies of the HIV subtype that is most commonly found in Europe and the United States (group M, clade B). Equivalent data are not available for HIV subtypes more commonly found in sub-Saharan Africa and in other parts of the world.

References

  1. Stekler JD et al. Learning from missed opportunities for HIV testing. Sex Transm Infect 85: 2-3, 2009
  2. BHIVA, BASHH and BIS UK national guidelines for HIV testing. September, 2008
  3. BASHH Statement on HIV window period. Available at www.bashh.org/guidelines, 15 March 2010
  4. Brenner BG et al. High rates of forward transmission events after acute/early HIV-1 infection. J Infect Dis 195: 951-959, 2007
  5. Malarelli F 'Diagnosis of Human Immunodeficiency Virus infection' in: Mandell, Bennett and Dolin, eds. Principles and practice of infectious diseases, 6th ed (online version), chapter 115. Philadelphia: Churchill Livingstone, 2007
  6. Wawer MJ et al. Declines in HIV Prevalence in Uganda: Not as Simple as ABC. Twelfth Conference on Retroviruses and Opportunistic Infections, Boston, abstract LB27, 2005
  7. Yerly S et al. The contribution of individuals with recent infection to the spread of HIV-1 in Switzerland: a 10-year survey. Fifteenth Conference on Retroviruses and Opportunistic Infections, Boston, abstract 512, 2008
  8. Hughes G et al. Recent phylodynamics of the HIV epidemic among MSM in the UK. Fifteenth Conference on Retroviruses and Opportunistic Infections, Boston, abstract 13, 2008
  9. Fiebig EW et al. Dynamics of HIV viremia and antibody seroconversion in plasma donors: implications for diagnosis and staging of primary HIV infection. AIDS 17:1871-9, 2003
  10. Kahn JO et al. Acute Human Immunodeficiency Virus Type 1 infection. NEJM 339:33-39, 1998
  11. Cohen MS et al. The detection of acute HIV infection. Journal of Infectious Diseases 202: S270-S277, 2010
  12. Busch MP et al. Time course of viremia and antibody seroconversion following human immunodeficiency virus exposure. Am J Med 102(5B):117-126, 1997
  13. Coombs RW Clinical laboratory diagnosis of HIV-1 and use of viral RNA to monitor infection. In Holmes KK (editor), Sexually Transmitted Diseases. New York: McGraw-Hill, 2008
This content was checked for accuracy at the time it was written. It may have been superseded by more recent developments. NAM recommends checking whether this is the most current information when making decisions that may affect your health.