Are there strains of HIV that aren’t detectable by modern testing?

Submitted by [deleted] t3_yvrfih in askscience

Are there strains of HIV that aren’t detectable by modern testing?

Hello all,

Are there any cases where an individual might test negative (outside of the window period) using HIV RNA PCR & antibody/antigen testing despite actually being positive?

Is it possible that someone might have some weird/rare mutation that causes the HIV RNA PCR test to not detect any HIV despite it being present?

If so, would that mutation also impact the HIV antibodies to where they are also not detectable?

Thank you for your time.

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iayork t1_iwg416j wrote

It's extremely unlikely that any strain of HIV will evade detection by either PCR or antibodies.

You probably misunderstand what's meant when we say HIV mutates a huge amount. Parts of the virus certainly do change wildly. but there are parts of it that stay very constant ("conserved"). And those parts have to stay constant, because they're what makes the virus a virus.

You can take a motorcycle and change its paint, swap out the handlebars, change the tires. You can even wrap it up in some lightweight costume and make it look like an X-wing starfighter for a parade, if you want. But if you pull out the pistons, or replace them with spaghetti, you don't have a functional motorcycle any more.

Tests for HIV don't depend on the equivalent of paint color or handlebars, they look for the functional components of the virus without which the virus can't replicate. For example, PCR tests often look for the Long Terminal Repeat (LTR), which are required for turning on the viral genes; these regions have minor variations, but can't change too much or the virus breaks.

The same is true with antibodies against HIV. Certainly there are antibodies against the rapidly-mutating regions, but for standard testing you don't look at those, you look at antibodies against the highly conserved regions.

(Why don't those antibodies against the highly conserved regions protect against HIV infection? Because, simplistically, many antibodies against any pathogen are not protective, and HIV has evolved so that the regions protective antibodies target do change rapidly.)

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badgerj t1_iwgirc1 wrote

This was brilliant! You had me at spaghetti! 🤪 Take this kind stranger!

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Savonlinna t1_iwhbb5z wrote

Are you missing a comma? If not, I feel I have to warn you: giving people away is generally frowned upon.

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BothObligation8722 t1_iwhyfp7 wrote

Yes extremely unlikely, but not certain. Several mutant CRF strains which standard tests are not developed for.

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GravitationalAurora t1_iwkizti wrote

I have a question;

(I'm a bachelor student of bioinformatics and I'm interested in these topics)

Some studies have shown that pathogenic retroviruses (for our immune cells) can infect fungi and bacterias as well, so if these kind of viruses go to the digestive system (specifically the large intestine) instead of blood vessels and somehow they find their suitable hosts among those microbiomes they can dominate there. So as long as they do not find their paths in blood they can be stealth even become as our normal flora (which means even body will support them) so these genomic based tests such as PCR can detect them? perhaps only stool exams? I mean at this situation the answer of this question is not "YES"?

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Sibaron t1_iwg2rn4 wrote

I would presume modern HIV PCR detection uses a variety of primers, that would in all likely cases detect the presence of the virus. The same is possible for the antibody test. However, it could also be that both tests target a gene or protein region that is so highly conserved it would never change. Thus any mutation would not be able to avoid detection. Any mutation significant enough that no primer or antibody would not effectively detect, would in all cases also affect the virus to a degree it would most likely be non viable. Even something as mutagenic as a virus or bacteria needs some conservation of specific regions to function properly.

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vestbio t1_iwgcnwq wrote

Thank you for your valuable time and reply.

But there are articles about updating kits later on where hiv O group could not be detected in the past. Likewise the pcr test cannot kill hiv-2. In addition to these, the HIV n and p group can also give false negatives. I have read many articles about them.

Could a new strain have arisen?

"Divergent hiv strain" among the false negatives on the website of the World Health Organization it is written

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Sibaron t1_iwgdg9i wrote

Kill HIV-2? Do you mean detect? HIV-2 is a another type of virus than HIV-1, therefore for it to detect both it would need target a common motive for both. HIV-1 test would not be made to detect HIV-2. You can get false positives and negatives in any test, and yes some might lead to more false negatives but the test can still detect them.

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NotFakeCable t1_iwgcys0 wrote

HIV-2 will test positive on today's 4th generation antigen/antigen testing, and the confirmatory antibody differentiation assay will identify it as HIV-2.

If you test HIV-2 by routine commercial PCR test, however, it will be negative. That's because routine commercial PCR tests only for HIV-1, while the HIV-2 PCR is a separate PCR order/test (and is a send-out at most centers in the US).

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googlecansuckithard t1_iwnqefs wrote

HIV is a fast mutator, such that there are new strains faster than they can be discovered - which is why the newer antivirals are of limited import 30 years down the road if medication access continues to be a problem of the gay community. As covid demonstrates, we should beware what other disease a virus with a large linear RNA mutation might bring the world least we get another incurable flesh eating virus. Hence HIV is still a life sentence in that you will forever properly be a pill head for life.

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