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Writer's pictureChristie Roberts
Dec 176 min read

U equals U

Arguably one of the biggest concepts in HIV, and medical, history. U=U means that undetectable equals untransmissable. But what does that actually mean?


The tl;dr version is that an undetectable HIV viral load means that you cannot transmit the HIV virus through sexual contact. If you don't want to read on, this is the key takeaway message, and it should be shouted from the rooftops. However, this isn't the tl;dr version, so buckle up pals...


What is a viral load?

Viral load is defined as the amount of HIV in the blood, or in other bodily fluids that would typically facilitate HIV transmission- semen, vaginal fluid, anal mucus and breast milk (Terrence Higgins Trust, 2024), and reflects the rate of viral replication (NICE, 2024). It is measured using a PCR blood test to check how many particles of the virus are present in a blood sample. Results are given as the number of viral copies per mL of blood (Terrence Higgins Trust, 2025).

Values range from over 1 million copies/mL, which indicates a lack of effective antiretroviral therapy (ART) and is associated with declining CD4 count and disease progression (NICE, 2024), to under 20 copies/mL, which is considered as an undetectable level in the UK (NICE, 2024; Terrence Higgins Trust, 2025).


It's been hypothesized and demonstrated in clinical trials since 1998 that effective ART reduces the risk of HIV transmission but it's a newer concept to be able to say that ART eliminates the risk when taken properly (i-base, 2017), and U=U messaging emerged. Several key trials led us to this conclusion.


The evidence

The PARTNER study (Rodger et al., 2016) was a key study which demonstrated this point. 548 heterosexual and 314 homosexual couples in 14 European countries were enrolled, and had over 58,000 instances of condomless anal or vaginal sex over a 4 year trial period (that's a huge amount of partners and sex!). Every couple was serodiscordant, i.e one person had HIV, and the other did not- historically, this would mean that condomless sex was a no-go. For inclusion in the study, couples had to be having condomless sex, and the partner with HIV had to be taking ART to suppress viral load with an HIV-1 RNA load less than 200 copies/mL.

The main outcome for the study was establishing the risk of within-couple HIV transmission to the HIV-negative partner- and the results were astounding. There were 0 cases of interpartner HIV transmission over 1238 couple-years of follow up (Rodger et al., 2016). Worth noting that 11 people did become HIV-positive over the course of follow up, but this was demonstrated by phylogenetic analysis to have come from someone who was not their main partner that they enrolled in the study with (i-base, 2016).

PARTNER provided an interesting new perspective on risk by reporting actual risks for a variety of different types of sex, rather than reporting on relative risks which is typically seen- i.e what is the risk of transmission if you are on ART versus not (i-base, 2016).


The PARTNER2 study (Rodger et al. 2019) built on the results of PARTNER, again recruiting couples from 75 sites across 14 European countries, but only including gay men, to allow for parity within the body of evidence. 782 gay couples were enrolled, racking up 76,088 instances of condomless anal intercourse during a 1593 couple-years period of follow up, with a median follow up period of 2 years. There was an HIV transmission rate of 0 within this cohort (Rodger et al., 2019). 15 men did acquire HIV during the study, but as above, this was not phylogenetically linked to their main partner, with 37% of HIV-negative men reporting sex with someone other than their main partner during the study.

The findings of this study correlate with the findings of the Opposites Attract study, which found zero interpartner transmission within 358 serodiscordant gay male couples in Australia, Thailand and Brazil, where one partner had an undetectable viral load and the other was not taking pre-exposure prophylaxis (Bavinton et al., 2018).


i-base (2017) have a really helpful resource outlining multiple studies demonstrating U=U, available here. I won't go through all the relevant studies, but PARTNER and PARTNER2 are widely hailed as 2 of the most influential studies.


How does ART work?

ART limits viral replication to prevent HIV from proliferating and causing the sequelae of events that leads to AIDS through decreasing CD4 levels and development of opportunistic infections. Typically, a person will be on a combination of medications to prevent mutation of the virus and drug resistance, and there are 5 main categories of ART which all act in somewhat different ways (NICE, 2024):

  • Nucleoside/tide reverse transcriptase inhibitors (NRTIs).

  • Non-nucleoside reverse transcriptase inhibitors (NNRTIs).

  • Protease inhibitors (PIs).

  • Integrase inhibitors (IIs).

  • Entry inhibitors (EIs)


Although ART will work to suppress viral loads, it cannot eradicate the virus and so treatment is lifelong. BHIVA (2023) recommend that all people living with HIV should be on ART, and that this should be commenced within 2-4 weeks after diagnosis, following assessing readiness to start treatment (European AIDS Clinical Society, 2024). It's worth noting that although HIV is no longer the death sentence it once was, receiving a diagnosis is still a life changing event.


There are really exciting developments in ART, including introduction of long acting injectable medications like cabotegravir and rilpivirine, taken monthly or 2 monthly, and newer long acting lenacapavir, taken 6 monthly in conjunction with tablets (aidsmap, 2024).


What does this mean?

It's a massive win for public health, for improving the lives of people living with HIV and their partners, and for reducing stigma around HIV, but sadly it's not an equitable win. The fact that we have the ability to prevent HIV transmission is huge but we have to recognise that access to ART to allow people to have an undetectable viral load is not evenly distributed across the world. This mainly impacts low and middle income countries due to the pharmaceutical industry's desire to put profit over people, blocking medications behind prohibitively expensive patents (STOPAIDS, no date). There may also be factors such as criminalisation of same sex relationships and HIV itself, and stigma or discrimination, which impede people being able to access not only treatment that would allow them to have condomless sex, but also save their life (UNAIDS, 2017; aidsmap, 2020).


The ability to have sex without condoms if desired can be a key factor in sexual health, as defined by the World Health Organisation (no date) which incorporates the 'possibility of having pleasurable and safe sexual experiences'. Having this knowledge that effective management of HIV in a serodiscordant relationship can lead to as normal a life as anyone else is so vital in protecting and promoting the sexual health and wellbeing of peopl living with HIV, alongside having marked impacts on mental health, as highlighted by Matthew Hodson in the aidsmap U=U consensus statement (aidsmap, 2017)


It's also pertinent to remind people that although condoms are not needed to prevent HIV transmission from people with an undetedtable viral load, condoms are still necessary for preventing other sexually transmitted infections. Also, unplanned pregnancy- although effective ART reduces the risk of vertical transmission from mother to baby from around 45% to less than 2% (Willey Lyatuu et al., 2023), with vertical transmission eliminated in some countries (The Lancet HIV, 2022).



As I expressed at the beginning of this post, the simple takehome message is that undetectable equals untransmissable. But, I hope this post has taught you a little more than that, and that you save this post for future reference. More importantly, spread the word! Tell your friends, family, colleagues and clinicians that U=U!!


Love,

Christie x


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