HIV and AIDS

False Negative Results On HIV Tests

Key points

False negative results most often occur when people test in the first few weeks after infection, during the 'window period'.

After this, they are extremely rare.

In most settings, the probability of a negative result being accurate is over 99.9%.

The ideal HIV screening test would correctly identify all HIV-positive and HIV-negative individuals 100% of the time. While many HIV tests are extremely accurate, they do not achieve 100% accuracy.

A false negative is a test result that says a person does not have HIV when, in fact, they do.

False negative results most often occur when people test in the first few weeks after infection, during the 'window period' of a test. At this time, the markers of infection (p24 antigen and antibodies) that tests look for may be absent or scarce. Tests cannot reliably pick up all cases of infection during the window period. For more information, read our page on window periods.

The chances of having a false negative result therefore depend on the rate of new HIV infections (incidence) in a community. In a low incidence setting, with very little ongoing transmission of HIV, most of the HIV infections which tests need to pick up will be infections that people have had for several months or years. For these long-standing infections, tests are extremely accurate and false negatives are therefore extremely rare. 

However, in a community with a higher HIV incidence and ongoing transmission of HIV, a higher proportion of the HIV infections which tests need to pick up will be recent infections (that people have only had for a few weeks). For these, tests are less reliable and false negatives may occur.

False negatives have also been reported in people taking antiretroviral medicines, whether as HIV treatment, pre-exposure prophylaxis (PrEP) or post-exposure prophylaxis (PEP).

False negatives after the window period

After the window period, in people who aren't taking antiretrovirals, false negative results are extremely rare.

The accuracy of a single HIV test depends in part on characteristics known as sensitivity and specificity. Sensitivity is an indication of test performance when testing people who do have HIV, whereas specificity reflects test performance in relation to people who do not have HIV. Many modern HIV testing devices are extremely sensitive (over 99%) and extremely specific (over 99%) in relation to long-standing HIV infection. There's more information on sensitivity and specificity on another page.

To some extent, the chances of having a false negative result also depend on how common HIV is in your community. When very few people among those testing actually have HIV, it is even more likely that a negative HIV test result is accurate. This is expressed by something known to healthcare workers as the 'negative predictive value'.

Glossary window period

In HIV testing, the period of time after infection and before seroconversion during which markers of infection are still absent or too scarce to be detectable. All tests have a window period, the length of which depends on the marker of infection (HIV RNA, p24 antigen or HIV antibodies) and the specific test used. During the window period, a person can have a negative result on an HIV test despite having HIV.

false negative

When a person has a medical condition but is diagnosed as not having it.

specificity

When using a diagnostic test, the probability that a person without a medical condition will receive the correct test result (i.E. Negative).

sensitivity

When using a diagnostic test, the probability that a person who does have a medical condition will receive the correct test result (i.E. Positive). 

incidence

The proportion of people who acquire an infection or develop a condition during a specified period of time. Incidence reflects newly acquired infections and conditions. See also 'prevalence'.

For example, take a test with 99.5% sensitivity and 99.5% specificity. If this test is used in a setting where 0.2% of people have HIV (for example, among the general population in the UK), the probability of a negative result being correct is 99.998%.

If the same test is used in a setting with a much higher HIV prevalence of 25% (for example, in the most heavily affected regions of southern Africa), the probability of a negative result being correct is marginally lower, at 99.832%.

Once the window period has elapsed (two months after possible exposure to HIV), if you test twice, using a different test device on each occasion, and both tests give a negative result, you can be confident that the result is accurate.

Find out more about the accuracy of HIV testing

For more information about HIV test accuracy, read our pages on sensitivity and specificity and on window periods. Our research briefings contain detailed information about the accuracy of fourth-generation combination tests, rapid point-of-care tests and self tests.

6 Abnormal Pap Smear Causes And What They Mean

The Pap smear, also called the Pap test, is the gold standard in cervical cancer screening. It detects precancerous cells and allow an opportunity to intervene, and it has helped to drastically reduce cervical cancer deaths since it started being used in the 1940s.

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During a Pap test, a healthcare professional will gently collect a few cells from your cervix with a tiny brush and then send them off to the lab for analysis. There, the cervical cells will be checked for any changes that may indicate cancer, or that may cause cancer later on.

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If the lab results show abnormalities in the cells, your doctor may wish to investigate further — but not always. Sometimes abnormal results are nothing to worry about. Many things can influence your Pap smear results, including where you are in your menstrual cycle or if you've recently had sex.

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Also, Pap smear abnormalities can be caused by a few other things besides cancer, like a sexually transmitted infection (STI) or a bacterial infection. If you get an abnormal Pap smear result, your doctor will explain what it indicates and what further testing or treatment you need, if any.

Here are six abnormal Pap smear causes and what they might mean.

1. Human Papillomavirus (HPV) According to the Centers for Disease Control and Prevention (CDC), the human papillomavirus is a common virus that is transmitted through sexual activity.

[4] In fact, HPV infection is the most common sexually transmitted infection (STI).

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A lot of the time, HPV infection can go away on its own, but in some cases, it may lead to cancer.

[5] There's a strong link between HPV and Pap smear abnormalities: Almost 70 percent of abnormal Pap smears are caused by HPV.

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There are many types of HPV. Some types of HPV can cause health problems, like genital warts, whereas other types can cause several cancers, including cervical cancer. HPV can cause cancer even if it doesn't show any symptoms.

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"Sometimes we need to understand what type of HPV is present to understand the next steps," explains Aparna Sridhar, MD, associate clinical professor of obstetrics and gynecology at the David Geffen School of Medicine in Los Angeles.

HPV infection can affect anyone who's sexually active, and generally it doesn't show any signs or symptoms. This is why, if you're diagnosed with the virus, it is important to discuss it with your sexual partner.

There is no treatment for the virus in itself, but there are treatments for the problems it causes. For example, if the biopsy reveals precancerous cells in your cervix, there are several options to remove them.

[7] In the case of genital warts, your doctor will prescribe medication or a surgical ablation procedure to get rid of them. Your healthcare provider will explain your options to you, depending on your situation.

The HPV vaccine protects against genital warts and most cases of cervical cancer. It is recommended for teens and young adults between ages 15 and 26. Although less beneficial, the HPV vaccine might be recommended for some adults between ages 27 and 45 who were not already vaccinated.

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The HPV vaccine may also be given to help with treatment for moderate or severe CIN.

2. Cervical Dysplasia (CIN) Cervical dysplasia is not cancer but an abnormality in the cells which, if left untreated, can lead to cervical cancer.

[8] Cervical dysplasia is also called "cervical intraepithelial neoplasia," or CIN for short.

There are many stages of cervical dysplasia. If you have mild or low-grade dysplasia, your doctor may simply choose to monitor you for the time being with follow-up exams until any further changes occur. "Early detection is key for identifying precancerous cells in the cervix and offering treatment or more surveillance," she adds.

For more advanced stages of dysplasia, your doctor will likely recommend removing the cells.

There are several ways to do so, including:

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Cryotherapy — a procedure that kills off the abnormal cells by freezing them

Minimally invasive surgery, which can involve cauterizing the cells with electricity or laser therapy

3. Cervical Cancer According to the National Cancer Institute (NCI), Cervical cancer is "cancer that starts in the cells of the cervix," the lower end of the uterus.

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Cervical cancer doesn't tend to cause any symptoms until it gets to more advanced stages, which is why screening is so important. And according to the World Health Organization (WHO), you should see your doctor if you experience any of the following:

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Unusual bleeding (which includes bleeding between periods, after menopause, or after you've had sex)

Unusual vaginal discharge or vaginal discomfort

Pain that won't go away in the back, legs, or pelvic area

Weight loss, fatigue, or loss of appetite

Swelling in the legs

Cervical cancer is a slow-growing cancer. It can take years, or sometimes even decades to develop. This is why, as long as you have routine exams, your healthcare professional will be able to detect abnormal or precancerous cells early enough to remove them before they develop into cancer.

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If you do get diagnosed with cervical cancer, remember that there are many treatment options available, ranging from minimally invasive surgery and immunotherapy (like for cervical dysplasia), to radiation therapy and chemotherapy.

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4. Trichomoniasis and Other STIs Pap smear abnormalities can also be caused by trichomoniasis, an STI caused by the parasite Trichomonas vaginalis. In women, trichomoniasis causes symptoms such as:

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Pain during sex

Vaginal discharge with a foul smell

Symptoms of a urinary tract infection, like pain or a burning sensation when you pee

Vaginal itching

Pelvic pain

If you're experiencing any of these symptoms, your doctor will likely take a sample of your vaginal fluid and examine it under a microscope. This is called a "wet prep microscopy."

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If you have trichomoniasis, you will need to take an antibiotic. This STI affects people of all genders, but it usually doesn't cause any symptoms in men. So, be sure to discuss your results with your sexual partner, as they will need treatment as well.

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5. Vaginal Infection An abnormal Pap test result can also indicate that you have a vaginal infection. But a vaginal infection doesn't necessarily mean an STI. For example, you may have an infection from bacteria (like in the case of bacterial vaginosis) or a fungus (like Candidiasis).

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Vaginal itching

Foul-smelling discharge

Pelvic pain

Bleeding between periods

Your doctor will recommend a form of treatment depending on the type of infection that you have. For example, if your infection is bacterial, you will have to take an antibiotic, but if it's fungal, an antifungal treatment is most likely.

Your doctor may also perform a follow-up screening test to rule out any additional problems.

6. Harmless Abnormal Pap Smear Causes There are many harmless reasons that a Pap smear can come back abnormal. If you have recently had sexual intercourse, this can affect the cells of the cervix. Having recently menstruated or being close to the start of your period can also cause cervix changes. Using tampons can affect the results, too.

[3] It is best to avoid these things before a Pap smear.

Most often, Dr. Sridhar says, "false results are due to lab errors." In fact, one study estimates that about 15 percent of all abnormal Pap test results are false positives.

[15]

According to the American Cancer Society, there are a few things you can do to make sure your Pap smear test is as accurate as possible:

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Schedule your test at least five days after your menstruation has stopped.

Avoid using tampons, spermicide gels, lubricants, or other vaginal creams or moisturizers for up to seven days before your test.

Avoid vaginal sex in the 48 hours leading up to your test.

The Takeaway

Pap smears are crucial for detecting cervical cancer, but they also detect abnormal cells before they've even started to become cancerous. Regular screening can help you get rid of these cells and carry on living a healthy life. Pap smears can also pick up signs of STIs and other infections that may need treatment.

Sensitivity And Specificity Of HIV Tests

Key points

The sensitivity of a test is the percentage of results that will be correctly positive when HIV is actually present. Lower rates of sensitivity will produce more false negative results.

The specificity of a test is the percentage of results that will be correctly negative when HIV is not present. Lower rates of specificity will produce more false positive results.

Both the sensitivity and specificity of the HIV tests that are widely used in the UK and comparable countries are usually above 99%.

Sensitivity

The sensitivity of an HIV test is defined as the proportion of people with HIV who will receive a positive result. In other words, a highly sensitive test is one that correctly identifies people living with HIV who take the test.

A test that is 100% sensitive would identify all HIV-positive people who take the test.

Many HIV tests have 99% sensitivity. A test with this sensitivity would identify 99% of HIV-positive people, but would miss 1% of them. They would get 'false negative' results.

A sub-optimal test, with only 94% sensitivity, would identify 94% of HIV-positive people, but miss 6% of them.

If you have a negative result on a highly sensitive test (for example, over 99%), it is highly unlikely you have HIV.

However, if you have a 'reactive' or 'positive' result, even with a sensitive test, that result needs to be confirmed with follow-up testing. If you rely on a single test result, it could be a false positive.

Specificity

The specificity of an HIV test is the proportion of people without HIV who will have a negative result. In other words, the specificity of a test refers to how accurate the test is when used by HIV-negative people.

A test that is 100% specific would give a negative result to all HIV-negative people who take the test.

Many HIV tests have 99% specificity. A test with this specificity would give correct results to 99% of HIV-negative people, but 'false positive' results to 1% of them.

A sub-optimal test, with only 94% specificity, would give a negative result to 94% of people who don't have HIV, but 'false positive' results to 6% of them.

The balance of sensitivity and specificity

In general, sensitivity and specificity exist in a state of balance. Increased sensitivity (the ability to correctly identify people who have HIV) usually comes at the expense of reduced specificity (meaning more false positives). Likewise, high specificity usually means that the test has lower sensitivity (more false negatives).

Therefore, healthcare services use a two-part testing procedure: a test with high sensitivity (to detect as many HIV-positive individuals as possible, allowing some false positives but very few false negatives), followed by a confirmatory test with high specificity (to eliminate as many of the false positives as possible).

How sensitive and specific are HIV tests?

Data on the sensitivity of tests are usually based on the detection of chronic (long-standing) HIV infection. A test that is highly sensitive to chronic infection may not perform so well in relation to acute (recently acquired) HIV. The period in which a test cannot reliably detect recent infection is known as the window period. For more information on testing people with recent infection, see our page on window periods.

"If you have a negative result on a highly sensitive test, you can rule out HIV."

Fourth-generation laboratory tests use a sample of blood and are the recommended tests in UK and US guidelines. These tests can detect both HIV antibodies (proteins produced by the immune system in response to a foreign substance) and p24 antigen (a protein contained in HIV's viral core that can be detected sooner than antibodies). Commonly used tests of this type include Abbott Architect HIV Ag/Ab, GS Combo Ag/Ab EIA and Siemens Combo HIV Ag-Ab. In virtually all studies, both sensitivity and specificity are above 99.5%, and are frequently reported as 100%. While third-generation laboratory tests are no longer recommended, they have similar sensitivity and specificity in relation to chronic infection. For more information, read our page on fourth-generation tests.

A wide range of rapid, point-of-care tests have been produced. Most can only detect antibodies, although some can also detect p24 antigen. There are considerable variations in the sensitivity and specificity of tests that are available around the world. However, the evaluation data that are available for tests that either have European CE marks or are approved by American regulators are more encouraging. World Health Organization evaluation of the Alere Determine HIV-1/2, Uni-Gold HIV, INSTI HIV-1/HIV-2 Antibody Test and SD BIOLINE HIV-1/2 3.0 found that all had a sensitivity and a specificity in the range of 99-100%. The sensitivity of the OraQuick Rapid HIV-1/2 is a little lower, especially when using oral fluid samples. For more information, read our page on rapid tests.

Glossary sensitivity

When using a diagnostic test, the probability that a person who does have a medical condition will receive the correct test result (i.E. Positive). 

specificity

When using a diagnostic test, the probability that a person without a medical condition will receive the correct test result (i.E. Negative).

chronic infection

When somebody has had an infection for at least six months. See also 'acute infection'.

false positive

When a person does not have a medical condition but is diagnosed as having it.

antibody

A protein substance (immunoglobulin) produced by the immune system in response to a foreign organism. Many diagnostic tests for HIV detect the presence of antibodies to HIV in blood.

Most self-testing devices are modified versions of rapid, point-of-care test kits that were originally designed for healthcare professionals. They have comparable sensitivity and specificity to the point-of-care tests. For more information, read our page on the accuracy of self-testing.

Self-sampling is different from self-testing. It involves you collecting your own sample and sending it to a laboratory for analysis. Fourth-generation assays are usually used to test the samples, so self-sampling can be expected to have the same sensitivity and specificity as fourth-generation laboratory tests. For more information, read our page on the accuracy of self-sampling. 

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