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Questions about U=U: what, when, who, why….?

The following questions provide more information about why an undetectable viral load stops HIV transmission (U=U).

What is U=U?

U=U is an abbreviation for:
Undetectable = Untransmittable

It means that someone with an undetectable HIV viral load on HIV treatment (ART) cannot transmit HIV, even without using condoms or PrEP.

U=U is also part of an international campaign to raise awareness about this benefit of ART. Currently, more than 720 organisations have joined from over 90 countries.

https://www.preventionaccess.org

What does U=U involve?

This protection using treatment (ART) depends on:

•   Being on stable ART for several months.

•   Having an undetectable viral load for several months – guidelines say six months.

•   Continuing to take your meds every day.

How can someone not be infectious?

The short answer is because when HIV viral load is undetectable, there is too little virus for an infection to occur.

Even though someone on ART is still HIV positive, HIV transmission is no longer a risk.

Most infections need a certain quantity or concentration of virus for transmission. For example, viral load might need to be above 500 or 1000 or 1500 copies/mL to be infectious. The actual upper limit is not known, but being undetectable is too low.

HIV is already quite a difficult virus to catch and being on ART reduces this risk to zero.

Does U=U work for everyone?

Yes. The PARTNER study included both gay and straight couples.

In some straight couples the man was positive and in others the woman was positive.

In PARTNER 1, about one-third of the 900 couples were gay men. PARTNER 2 included 1000 gay couples.

In PARTNER 1, couples had sex more than 58,000 times without condoms. In PARTNER 2 this figure was 77,000 times. There were no linked HIV transmissions in either study.

Does this work with all HIV drugs?

Yes. The exact combination is not important.

U=U only needs viral load to be undetectable.

All ART that does this will mean U=U.

Does U=U work for all types of sex?

Yes. The PARTNER study collected information about the different sex people had. For example, the numbers of times people had oral, vaginal or anal sex. It also asked whether the negative partner was active or passive. It included whether there was ejaculation.

PARTNER reported zero transmissions for everything.

This included sex with the highest HIV risk – ie being the receptive partner for anal sex.

Does this mean I can stop using condoms?

Whether you use condoms is a personal choice. Or hopefully it is a mutual choice with your partner. Condoms are good at stopping many STIs and they are an effective contraceptive to stop pregnancy.

But if HIV is the only concern, then in the context of U=U, there is no reason to continue to use condoms.

For people who are happy using condoms for other reasons, this will still be an important choice.

My partner is HIV positive and still wants to use condoms?

Your partner has to come to their own decision about what is right for them.

They might want to use condoms for other reasons. Or they might still worry about HIV transmission.

Sometimes it takes time for someone to accept new evidence. Especially if they have been using condoms for many years.

My partner is HIV negative and still wants to use condoms?

Your partner has to come to their own decision about what is right for them.

They might want to use condoms for other reasons. Or they might still worry about HIV transmission.

Sometimes it takes time for someone to accept new evidence. Especially if they have been using condoms for many years.

Is U=U now widely believed?

Yes, most leading HIV scientists and doctors now agree with the U=U statement.

These experts are all convinced by the increasing evidence from many different studies.

Scientists are trained to be cautious. They need to be convinced by the evidence before they making factual statements. Although it took a long time for the evidence for U=U to be accepted, the world’s leading HIV doctors and organisations now strongly support U=U.

For example, Professor Chloe Orkin, chair of the British HIV Association (BHIVA) said:

“There should be no doubt that a person with sustained, undetectable levels of HIV in their blood cannot transmit HIV to their sexual partners”.

Similar statements have been made by the International AIDS Society (IAS) and the US Center for Disease Control (CDC).

Do STIs affect the zero risk?

U=U still works if, without realising it, one or both partners has an STI.

The PARTNER study included couples where STI rates were reported, usually in the context on an open relationship. Although routine check-ups for STIs are important, with treatment if needed, there were still no HIV transmissions.

It is only when ART is not used that the risk of HIV transmission becomes higher if either partner has an STI.

Will my doctor and health workers know about this?

Hopefully, yes. U=U has been headline news for at least two years.

U=U is also included in HIV treatment guidelines.

However, just as leading experts took time to accept the evidence, some doctors are slow to discuss U=U with all their patients.

For many years, condoms were the main way to protect against HIV. This is no longer the case. New studies prove that both U=U and PrEP are more effective than just relying on condoms.

U=U is included in the BHIVA Standards for HIV Care (2018). If your doctor doesn’t tell you about U=U, then ask them why.

How long does viral load need to be undetectable?

Guidelines recommend having an undetectable viral load for six months before relying on 100% protection from U=U.

This is a cautious approach, and is why guidelines refer to being on “stable ART”.

It usually takes up to 3 months for viral load to become undetectable. This depends on your choice of meds. If viral load was very high when you started ART, it can sometimes take longer to become undetectable.

Because it can take longer for viral load to become undetectable in genital fluids, guidelines recommend waiting six months after viral load is undetectable in blood.

What if I forget to take my meds one day?

Missing your meds once or occasionally will not change U=U.

This is because viral load will still be undetectable.

Good adherence is important, but you would probably need to miss HIV meds for 2-3 days before viral load becomes detectable.

If you do miss ART for several days, it is important to check your viral load is still undetectable before relying again on U=U. This is importance for avoiding drug resistance as well.

Good adherence is essential for U=U.

U=U depends on not regularly missing your HIV meds.

What about viral load blips?

Sometimes viral load results can “blip” above 50 and go back to undetectable without changing treatment. Any result less than 200 copies/mL will not affect U=U.

In the PARTNER studies, undetectable viral load was defined as being less than 200 copies/mL.

Is there a risk viral load can rebound to higher levels?

In the context of good adherence, viral load doesn’t rebound.

Once viral load has been undetectable for over six months, then so long as you take your meds, they will continue to work. Good adherence is essential.

A drug interaction that reduces your HIV drugs might have a risk of viral load rebound. This just means checking with your pharmacist or doctor that and new meds or supplement (including over-the-counter) don’t interact with your ART.

Less than 5% of people on stable ART have viral load each year and these cases of rebound are nearly always linked to lower adherence. The chance gets lower with every year you are on ART.

How do we know undetectable viral load is so effective?

Researchers have known for over 20 years that ART reduces the risk of transmission.

It is only in the last few years however, that it became clear that transmission is stopped completely.

In 2007, some doctors were already so convinced that they published a document called the Swiss Statement. Since then several studies have provided more evidence.

The most important of these were the two PARTNER studies. Each study enrolled aoround 900 serodifferent couples (where one partner was HV positive and the other HIV negative).  The positive partner needed to be on ART with an undetectable viral load and the couple needed to be having sex without condoms. In PARTNER 1, about one-third of the couples were gay men and in PARTNER 2 all the couples were gay men.

PARTNER 1 reported zero linked HIV transmissions after more than 58,000 times the couples had sex without condoms. In PARTNER 2 this figure was 77,000 times.

In the few cases where the negative partner did become HIV positive, this was always from outside the relationship. The study was able to prove this by comparing the structure of the different viruses.

What is the difference between “zero” and “very low”?

In the case of U=U, the difference between zero risk and a very small risk is a technical detail that is not important in practice.

Technically, even if the true risk is zero, it is not possible to prove something will not happen. Instead, the scientific approach is to define a possible risk, however small. For example, one in a million etc. This is easy to do with low risk activities, but with zero risk activities, there is nothing to measure.

In these cases a very small theoretical risk is effectively zero. This is why scientists are happy to say the risk for U=U is now zero.

The risk is not “greatly reduced”, it is not “negligible”. The risk is zero.

In more than ten years since the Swiss Statement was published in 2007, there have been no proved case reports of HIV transmission with undetectable viral load.

Even if in the future, a case is reported, the absolute risk would be so low for this to still be effectively zero.

Does U=U apply to other ways that HIV is transmitted?

Having an undetectable viral load on ART also reduces the risk of other ways that HIV is transmitted.

However, it doesn’t reduce other risks to zero.

For example, a baby can still become HIV positive from breastfeeding, even if the mother has an undetectable viral load.

The risk of transmitting HIV from sharing drug injecting equipment is higher than sexual transmission. There isn’t evidence to support this risk being zero.

What is the evidence to support U=U?

The evidence for U=U is detailed in the following articles. This covers many different types of studies from the last 20 years.

The evidence for U=U (Undetectable = Untransmittable): why negligible risk is zero risk
http://i-base.info/htb/32308

Individual results from key studies and the Swiss Statement are included below.

ZERO: no linked HIV transmissions in PARTNER study after couples had sex 58,000 times without condoms (2016)
http://i-base.info/htb/30108

Q&A on the PARTNER study: how to interpret the zero transmission results (2016)
http://i-base.info/qa-on-the-partner-study

Gay men with undetectable viral load do not transmit HIV: Opposites Attract study supports U=U (2017)
http://i-base.info/htb/32190

Treatment is prevention: ARV treatment in HPTN-052 reduces transmission by at least 96%: single transmission in treatment arm occurred prior to viral suppression (2011)
http://i-base.info/htb/15455

HPTN 052: no HIV transmissions on effective ART – long-term follow-up (2015)
http://i-base.info/htb/28715

The Swiss Statement (2007)
http://i-base.info/qa/factsheets/the-swiss-statement