HIV-1/2 Antigen/Antibody (4th Generation)

A blood test that looks for HIV antibodies and a viral protein (p24), so it can find an infection earlier than tests that only look for antibodies.

AI-verified against cited sources. Awaiting expert reviewAlso called HIV Ag/Ab, HIV Combo, HIV-1/2 Ag/AbLOINC 56888-1

What it is

This is the usual first test for HIV. It looks for two things: antibodies your body makes against HIV-1 and HIV-2, and p24, a protein from the virus itself. Because it checks for both, it can pick up an infection sooner than older antibody-only tests. The result is printed as non-reactive (negative) or reactive. A reactive result is not a final answer. Labs run more tests on the same sample to confirm it.

Why it matters

Finding HIV early lets a person get care sooner and protect partners. This test is part of many routine checkups, pregnancy visits and sexual health panels. A non-reactive result means no signs of HIV were found in that sample. A reactive result starts a set of follow-up tests that sort a true infection from a false alarm.

If it’s high

Reactive means the test found something it flags as a possible sign of HIV. On its own this is a screening result, not a diagnosis. Labs follow a reactive screen with a second test that tells HIV-1 from HIV-2 antibodies, and sometimes a test for the virus's genetic material (RNA). Those tests show whether the infection is real. A small share of reactive screens turn out to be false alarms.

Common causes

A false-positive screening result that follow-up tests do not support
HIV infection, either recent (acute) or long-standing
A specimen mix-up or labeling error (rare), which is one reason a new sample is sometimes drawn
Some autoimmune conditions, which have rarely been linked to false-positive results

What can help

Ask your clinician which follow-up tests are being run on your sample and when results will be ready
Ask whether any precautions with partners make sense while you wait for the follow-up results
If the follow-up tests are positive, ask what care and support are available

If this applies to you

HIV Ag/Ab means a little more for some people. Open the one that fits you.

Taking HIV PrEP

An HIV test comes right before starting PrEP and at follow-up visits. The CDC suggests testing at least every 3 months on daily pills and every 2 months with cabotegravir shots. With lenacapavir shots, a test is done before each 6-month injection.

Blood tests on HIV PrEP

What can affect your result

Timing: very early in an infection the test can be non-reactive
A reactive screen can be a false alarm, which follow-up testing sorts out
Age: in babies under 2 years, antibody tests can reflect the mother's antibodies
Rapid and home tests use other methods. A reactive rapid test is followed up with a lab test like this one
In the first weeks after infection the test can still be non-reactive, because there may not yet be enough virus protein or antibody to detect.
A screening result can be reactive even when there is no HIV (a false positive). CDC reports that causes have included specimen mix-ups, labeling errors and autoimmune disorders, which is why follow-up testing is built in.
In babies and children up to 2 years, antibody tests can reflect antibodies passed from the mother, so virus (RNA) tests are used to diagnose infection (Mayo Clinic Laboratories).

CDC and APHL (2014) estimate HIV-1 RNA becomes detectable about 10 days after infection. The p24 protein appears about 4 to 10 days after that, and IgM antibodies about 10 to 13 days after RNA first appears.

When to talk to a clinician

Talk with a clinician promptly about any reactive result rather than waiting for a routine visit. If you may have been exposed to HIV in the last few days, contact a clinician or urgent care right away to ask about time-sensitive preventive options.

Questions you could ask

How long after a possible exposure should I test again?
How often should I be screened, given my situation?
Which follow-up tests will you run on this sample, and when will I get those results?
Should I take any precautions with partners until the follow-up results are back?
What support is available while I wait?

Questions people ask

What makes this a 'fourth-generation' test?

It looks for HIV antibodies and also for p24, a protein from the virus itself. The protein shows up before antibodies do, so this test can detect an infection earlier than tests that only look for antibodies.

My screening test was reactive. Does that mean I have HIV?

Not by itself. It is a first step. The lab runs a second test that tells HIV-1 from HIV-2 antibodies, and sometimes a test for the virus's genetic material. CDC and APHL report that FDA-approved fourth-generation screens correctly read 99.50% to 100% of people without HIV as negative, but false alarms still happen, which is why follow-up is built in.

Can a non-reactive result be wrong if I test soon after a possible exposure?

Yes. In the first weeks after infection there may not be enough virus protein or antibody to detect. If your exposure was recent, ask your clinician when to test again. Tests for the virus's genetic material can find an infection earlier than this one.

Show the science and sources

For clinicians and researchers

Fourth-generation combination immunoassay for HIV-1/HIV-2 antibodies and HIV-1 p24 antigen. Mayo Clinic Laboratories runs an electrochemiluminescence immunoassay (ECLIA) and lists 'Negative' as its reference value; a reactive screen reflexes to an HIV-1/HIV-2 antibody confirmation/differentiation test, and then to HIV-1/HIV-2 RNA detection for some outcomes. Mayo's routine screen is not meant for people with symptoms or for pregnancy testing, which have separate orderable tests there. Many platforms also print a signal-to-cutoff ratio. Cutoffs are assay-specific and the ratio is not a viral load. The CDC/APHL algorithm (2014, with CDC's 2018 quick reference update): a nonreactive screen needs no further testing, unless a recent exposure is suspected, in which case an HIV-1 NAT or a repeat test on a new specimen is advised. A reactive screen goes to an HIV-1/HIV-2 antibody differentiation immunoassay. If that is nonreactive or indeterminate, an HIV-1 NAT is run. A reactive NAT indicates laboratory evidence of acute HIV-1 infection. A negative NAT with a nonreactive or HIV-1 indeterminate result indicates a false-positive initial immunoassay, and a negative NAT with a repeatedly HIV-2 indeterminate or HIV indeterminate result is referred for a different HIV-2 test or repeated in 2 to 4 weeks. CDC/APHL describe marker kinetics of RNA at about 10 days, p24 antigen 4 to 10 days later and IgM antibody 10 to 13 days after RNA. In their evidence review, FDA-approved fourth-generation assays had sensitivity of 99.76% to 100% for established HIV-1 infection and specificity of 99.50% to 100%. Limits: rare persons stay antibody-negative despite detectable RNA, and false positives have been attributed to specimen mix-up, mislabeling and autoimmune disorders. The 2014 report notes that acute HIV-2 infection could, in theory, give a reactive screen with a nonreactive differentiation result and a negative NAT, so HIV-2 follow-up is suggested if clinically indicated. Serologic tests cannot distinguish neonatal infection from passively acquired maternal antibody in children up to 2 years (Mayo), so virologic tests are used there; the CDC/APHL recommendations cover people aged 2 years or older.

LOINC 56888-1 (primary), 58900-2, 105080-6, 108720-4. Specimen: serum-or-plasma.

Sources

Laboratory Testing for the Diagnosis of HIV Infection: Updated Recommendations, CDC and Association of Public Health Laboratories (2014)
HIV-1 and HIV-2 Antigen and Antibody Routine Screen, Serum (test HIVSS), Mayo Clinic Laboratories (Extended Catalog)

AI-verified against cited sources. Awaiting expert review. Last reviewed 2026-10-03. How we build and check these pages.