Explanation

HIV-1/2 combination test (antigen and antibodies): what is measured?

This is a fourth-generation combination test. It looks for two things at the same time: the p24 antigen, a protein of HIV-1 (human immunodeficiency virus) that enters the blood shortly after infection, and antibodies that the body makes against HIV-1 and HIV-2. Because the test also looks for the virus itself, an infection is found earlier than with a test for antibodies only. The time between infection and a positive test is called the window period.

What can it detect?

An HIV infection (HIV-1 or HIV-2), even if it causes no symptoms (yet)
A recently caught HIV infection, usually from a few weeks after infection

Result

What does the result mean?

Positive result

A positive (reactive) result means that the test has found p24 antigen or antibodies against HIV. This is not yet a diagnosis: a small share of reactive results is false-positive. The laboratory therefore does a confirmation test (immunoblot) itself on the same blood, as the LCI guideline (RIVM) prescribes; this also shows whether it is HIV-1 or HIV-2. Only a positive confirmation test proves an HIV infection. HIV cannot be cured, but with HIV inhibitors and timely treatment, life expectancy is almost the same as that of people without HIV. Someone who is treated well and has an undetectable amount of virus can no longer pass on HIV through sex (undetectable means untransmittable).

Negative result

A negative result means that no p24 antigen and no HIV antibodies have been found. According to the LCI guideline (RIVM), a combination test like this one can become positive from about 2 weeks after infection, and 6 weeks after infection it is positive in 99 out of 100 infected people. A negative result 12 weeks or longer after the last risk contact rules out an HIV infection. If the contact was more recent, a repeat test is needed. When using PrEP or PEP (HIV inhibitors to prevent infection), the window period can be longer.

After an abnormal result

The laboratory confirms a reactive result itself with an immunoblot on the same blood. If that is also positive, the amount of virus (HIV RNA) is usually measured in a second blood sample. If the combination test is reactive but the immunoblot is negative, it may be a very early infection; with a high risk, the LCI guideline (RIVM) then advises a test for HIV RNA. With a confirmed infection, a quick referral to an HIV treatment center follows, along with a test for other STIs and a discussion about warning sexual partners. HIV is not notifiable; new diagnoses are, however, registered by Stichting HIV Monitoring.

Reliability

How reliable is the test?

According to the LCI guideline (RIVM), fourth-generation combination tests have a very high sensitivity and specificity, and measuring the p24 antigen has shortened the window period to 2 to 4 weeks after infection. False-positive results occur to a small extent; the laboratory itself confirms every reactive result with an immunoblot. The main cause of a false-negative result is testing within the window period; according to the guideline, only a negative test 12 weeks after the last risk contact rules out HIV.

What can affect the result?

Within 12 weeks after the last risk contact, a negative result does not fully rule out HIV, and within 2 weeks it says little; with symptoms of an acute infection or a recent high risk, the doctor can order a test for the virus itself (HIV RNA).
Using PrEP or PEP suppresses the virus and can lengthen the window period or give an unusual pattern of antigen and antibodies.
A reactive result can be false-positive due to cross-reactivity or a nonspecific immune reaction; only the confirmation test gives a definite answer.
In children younger than 18 months whose mother has HIV, antibodies from the mother can be present; this test is not suitable for them.
The p24 antigen test in this combination test is aimed at HIV-1; an infection with HIV-2 is only found through the antibodies.

Who it is for

Who is the test useful for?

Useful for

Useful after sex without a condom with a new or changing partner, for men and transgender people who have sex with men, sex workers, people who inject drugs, people from (or with a partner from) an area where HIV is common, if a partner has HIV, and with symptoms or conditions that may fit HIV (such as another STI or hepatitis B or C). If the risk contact was less than 72 hours ago, quick contact with the GP or the GGD (municipal public health service) about PEP is more important than a test. Pregnant women are already tested as standard by their midwife.

How common is it?

At the end of 2024, 23,105 people with HIV were registered with the HIV treatment centers in the Netherlands; in 2024, 1,013 new registrations were added. In the Netherlands, HIV mainly occurs in men who have sex with men. In heterosexual men and women who get tested at the sexual health centers, HIV is found in about 1 in 1000 or fewer.

RIVM based on Stichting HIV Monitoring (2024); LCI guideline on HIV infection (detection rates at sexual health centers)

Drawbacks and risks

A reactive result that turns out to be false-positive in the confirmation test can cause a lot of worry until then.
Testing within 12 weeks after a risk contact can give false reassurance if no repeat test follows.

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