AGAIN: U=U {If You Are Undetectable You are NOT Transmissible} This Is True Anywhere in The Planet
Slide from John Blandford's presentation on Vietnam's K=K campaign
In Guatemala, the slogan is “Indetectable = Intransmisible” (I=I); in the Netherlands, it’s “Niet meetbaar = Niet overdraagbaar” (N=N); and in Turkey, “Belirlenemeyen = Bulaştırmayan” (B=B). One of the most striking aspects of yesterday’s pre-conference on “Undetectable = Untransmittable” (U=U), held in advance of the 22nd International AIDS Conference (AIDS 2018) in Amsterdam, was the extent to which the campaign has energized advocates around the world.
“U=U is a fact that every person with HIV around the world should know about,” said Jesús Aguais of AID for AIDS International, an organization working in six Latin American countries. “People have the right to be informed and it is our responsibility to disseminate this information.”
“I can’t believe this information has been known for ten years and I’ve only heard about in the past six months,” commented Lucy Wanjiku-Njenga of Positive Young Women’s Voices. She said that not many of her peer group in Kenya know what U=U means. Those who do know about it heard about it from a friend or on social media, rather than from a doctor or care provider.
The quotes she presented from other young women testified to the impact the U=U message can have:
“This is a message of hope to those living positively. It is the success that comes along with adherence. The victory after all those days you feel like the drugs were a burden. With this, young women can lead a life without worry of infecting their partners.”
“U=U gives young people who acquired HIV through vertical transmission like me a sense of ‘normalness’. For the first time, I see I am not afraid of infecting someone else because I am virally suppressed! I can finally have a fear-free relationship. I am the safest relationship any guy can have!”
Alex Schneider’s organisation Life4me+ works across Eastern Europe and Central Asia. For him, the Russian language slogan “НЕОПРЕДЕЛЯЕМЫЙ = НЕ ПЕРЕДАЮЩИЙ” (Н=Н) is a new tool for advocacy. It can help raise broader public awareness of HIV, reduce stigma towards people living with HIV, undermine self-stigma, increase HIV testing, motivate early initiation of treatment and improve treatment adherence. So far, 60 organisations, including eleven state organisations, have signed on to the statement in the 14 countries of the region.
Nonetheless, there are very real barriers to treatment in the region, including frequent stock-outs of medication. In terms of the 90-90-90 targets, currently 63% of people with HIV are diagnosed, 28% of those diagnosed are on treatment, and 22% of those on treatment are virally suppressed.
In many low- and middle-income countries, viral load monitoring is not routinely available, making it impossible for an individual to be confident that they really are undetectable. U=U provides an additional argument for increasing access to viral load monitoring.
In Vietnam, the Centers for Disease Control and Prevention (CDC) has promoted the slogan “Không phát hiện = Không lây truyền” (K=K). John Blandford of the CDC said that the campaign was conceived as an intervention that would both support changes in HIV care and reduce stigma. The information has been shared via social media, in community meetings and through press coverage.
The community advocacy has helped build support among people with HIV and healthcare practitioners for a switch from CD4 to viral load monitoring. The country’s treatment guidelines are now aligned with K=K, so that a key marker of success is two consecutive viral load test results of less than 200 copies/ml. The proportion of people having their viral load monitored increased from 21% to 73% in a year, with 93% of those on treatment now being virally suppressed.
Science
The pre-conference opened with Anthony Fauci, probably the United States’ most senior HIV research scientist, reviewing the evidence that underpins U=U. Since the mid 1990s, data showing the inverse relationship between the level of virus and the rate of HIV transmission have been accumulating. The introduction of combination therapy “was the definitive moment of U=U and we didn’t even realise it then,” he said.
The research studies HPTN 052, PARTNER 1 and Opposites Attract have provided the strongest evidence. Tomorrow the final results of PARTNER 2, the study which more precisely quantifies the potential for HIV transmission during anal sex, will be presented at AIDS 2018. It is likely to be the most discussed study at this year’s conference.
Nonetheless, Fauci did not feel he needed to wait for these results to state: “The evidence that undetectable equals untransmittable is overwhelming.”
Pietro Vernazza was presented with a lifetime achievement award for the 2008 Swiss Statement he co-authored and other work which has laid the basis for U=U. Clearly moved by the advocates’ response to his work, he went back to the philosophy of science to explain why he felt that the accusation of the Swiss Statement not being founded on evidence was unfair.
If the hypothesis is that HIV can be transmitted when a person is taking effective antiretroviral therapy, then the null hypothesis is that HIV cannot be transmitted in these circumstances. In science, it is the null hypothesis which a researcher aims to disprove or falsify.
He said that the position of the ‘HIV establishment’ had always been the former, that there remains some transmission risk when a person has an undetectable viral load. He said it was up to those who hold that position to find a single documented case of transmission from a person with a durably suppressed viral load.
Vernazza quoted the logical philosopher Irving Copi: “In some circumstances it can be safely assumed that if a certain event had occurred, evidence of it could be discovered by qualified investigators. In such circumstances it is perfectly reasonable to take the absence of proof of its occurrence as positive proof of its non-occurrence.”
Breastfeeding
One remaining area of scientific uncertainty concerns breastfeeding. Eliane Becks Nininahazwe, a woman from Burundi living in the Netherlands, said that many women were waiting for the day when they could feel confident that U=U applies to breastfeeding. “Please people who are doing the science, hurry up!” she said.
Linda-Gail Bekker of the Desmond Tutu HIV Centre said that there are still gaps in the data, but there is clearly a strong relationship between viral load and the potential for transmission.
She pointed to two African cohorts (from Tanzania and Malawi) with a total of 477 infant-mother pairs in which no HIV transmissions have occurred from mothers with a plasma viral load below 100 copies/ml. However, some transmissions occurred in the latter study from women whose viral load would be described as ‘undetectable’ using a higher cut-off. This could be due to viral load being detectable between the (relatively few) occasions when it was measured, or due to reservoirs of virus in breastmilk that can’t be eliminated by antiretroviral therapy.
Even if she could not be definitive, Bekker said that her take-home message was that women taking HIV treatment who have an undetectable viral load have shown very little risk of HIV transmission. Weighing up the multiple benefits of breastfeeding for the infant with this low transmission risk, she said that it was appropriate that women in low- and middle-income countries continue to be recommended to exclusively breastfeed for six months after birth.
Pietro Vernazza said he had reviewed the same body of evidence to consider recommendations for the high-income setting of Switzerland. For an optimal scenario of a woman who was adherent to her medication and had a suppressed viral load of below 50 copies/ml throughout pregnancy and breastfeeding, his group had not been able to identify any confirmed cases of HIV transmission. While there are still gaps in the data, this risk needs to be considered alongside the proven benefits for all infants, such as fostering contact between mother and child, the anti-inflammatory and antimicrobial substances contained in breastmilk, and the development of the gut microbiota.
Given clinicians’ uncertainty about the balance of potential harms and benefits, he suggested that a shared decision-making approach was appropriate. Breastfeeding should not be actively promoted to women living with HIV in Switzerland, but women who choose to breastfeed should be supported by their clinical teams, in particular with adherence support and regular viral load monitoring.
Messaging
How can organisations describe U=U in a way which is meaningful to people living with HIV, their sexual partners and the general public? Whereas the concepts of ‘treatment as prevention’ (TasP) and ‘universal test and treat’ (UTT) are rooted in public health and describe the impact of widespread treatment in a population, ‘undetectable = untransmittable’ focuses on the individual. The slogan has already reached far more people living with HIV than the idea of TasP ever did, but the language used is complex and may not reach the widest audience.
Michael Brady said that it was in 2016, after the second release of data from the PARTNER study, that the UK organisation the Terrence Higgins Trust decided it had a responsibility to share the information in a clear and definitive way. They would have to evolve the language, so that it would be clear, concise and easily understood, he said.
A number of slogans were tested, including “Yes we are sure”, “This changes everything”, “Won’t pass it on” and “Can’t be passed”. Two made it to the shortlist – “I’m not a risk” (which resonated most with people living with HIV) and “Can’t pass it on” (which had greater purchase with the wider public).
It was the latter slogan which has been taken forward. Without a larger than usual budget, it has been one of Terrence Higgins Trust’s most successful campaigns in terms of reach and exposure, especially on social media. Brady attributed this to the simplicity and definitiveness of the message, as well as the support of community advocates.
Nic Holas of the Australian online organisation the Institute of Many said that having people with HIV understand U=U was only half the battle. They needed their sexual partners and potential sexual partners to understand it as well. A particularly important audience are pre-exposure prophylaxis (PrEP) users and his organisation has developed a series of videos in collaboration with Dynamix International, one of the main companies importing generic PrEP medication to Australia, the UK and elsewhere.
While PrEP and U=U are often described as having synergies, he pointed to tensions between the two approaches. Some PrEP users remain fearful of and stigmatising towards people with HIV, he suggested. They prioritise their new found freedom but ignore the fact that PrEP could only be developed “after people with AIDS put their bodies on the line”.
“In the age of PrEP, people living with HIV must not shy away from taking up space and ensuring our voices are heard,” he said. “It is not enough to end the HIV epidemic with PrEP and leave us isolated, criminalised and stigmatised.”
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