Spotlight Center on HIV Prevention Today


The Evidence for U=U: Why Negligible Risk Is Zero Risk

August 10, 2017

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Over the last year, hundreds of HIV organisations have joined a new campaign to endorse the statement that HIV transmission does not occur when viral load is undetectable on ART.

And while the dramatic impact of ART on reducing HIV transmission has been known for a long time, it is new to say ART stops transmission completely.

This change is especially important given that prejudice and discrimination against HIV positive people is still widespread. So while it is easy to simply answer "no" to the question of whether someone with an undetectable viral load is still infectious, it is more complicated to explain why.

This article summarises selected key studies from 20 years of accumulating evidence that should directly challenge the prejudice and fear of HIV that is still widespread.


U=U: Undetectable = Untransmittible (or Uninfectious)

Launched in 2016, the Undetectable = Untransmittable (U=U) campaign is based on the following statement: "A person living with HIV who has undetectable viral load does not transmit HIV to their partners".1,2

The statement has been endorsed by more than 350 HIV organisations from 34 countries, including by leading scientific and medical organisations such as the International AIDS Society (IAS), UNAIDS, and the British HIV Association (BHIVA).2

The support for the statement is also remarkable given that science is not able to prove a negative -- ie that something will not happen.

Instead, people who claim that HIV is transmittable when viral load is undetectable, should be challenged to prove it.

20 Years of Accumulating Evidence

The scientific approach to understanding the world usually involves three stages.

  1. Observing something.
  2. Deciding on one or more hypotheses that might explain it.
  3. Testing any theory in a suitable experiment.

The strength of this approach is that a good study, by definition, should be repeatable. If the results are true and not by accident, other researchers should be able to repeat the study and get similar and consistent results each time.

The evidence supporting U=U includes different types of research spanning observational studies, randomised trials, systematic reviews and expert opinion (see Table 1).

Key stages in this timeline include:

  • 1998: observations that triple therapy ART reduced transmission.
  • 1998: expert opinion that risk would be reduced (including based on reviewing evidence related to the details of this protection).
  • 2000 -- 2005: prospective observational studies and related research (Rakai cohort and others).
  • 2008: further expert opinion and evidence review (Swiss Statement).
  • 2011: first evidence from a randomised clinical trial (HPTN 052).
  • 2014 -- 2017: further prospective observational studies (PARTNER and Opposites Attract) -- the first studies to provide data about risks for gay men.
  • 2016 -- 2017: further expert opinion (U=U campaign).

Each of these studies is now explained in more detail.

Early Evidence: Mother-to-Child And Ugandan Heterosexual Couples

A remarkable report in July 1998 provided some of the first clinical evidence for the impact of viral load on HIV transmission.

At the IAS conference held in Geneva, Dr Karen Beckerman reported on a small cohort of HIV positive women in San Francisco who had used triple therapy during pregnancy. Instead of the 30% mother-to-infant transmissions reported before ART, or the 10% seen with AZT monotherapy, triple therapy reduced transmissions to approaching zero.3

Although this study reported on vertical rather than sexual transmission it provided clinical results showing that an undetectable viral load stopped a much higher risk of transmission.

Then later that year, the December 1998 update to the US DHHS guidelines, included "possibly decreasing the risk of viral transmission" as an additional reason for starting ART.4

These expert guidelines noted the lack of direct evidence supporting this statement and emphasised that condoms should still be used even with undetectable viral load -- but this inclusion in the 100-page document from leading US doctors this was important.

One of the next key studies provided direct evidence linking viral load with risk of HIV sexual transmission. This was a prospective observational cohort study in 415 serodifferent heterosexual couples in Rakai, Uganda, where one partner was HIV positive and the other was HIV negative. The study, by Thomas Quinn and colleagues was published in the New England Journal of Medicine in 2000.5

After median follow-up of 22 months, the risk of HIV transmission was not only clearly linked to higher viral load. No transmissions were reported among the 51 couples where the HIV positive partner had viral load below 1500 copies/mL.

Several details of the Rakai study are important. It was before ART was available and condom use was low. It found that transmissions rates were similar for men and women and that other STIs didn't affect HIV risk. It also reported highly significant impact from circumcision -- all the men who became positive during the study were uncircumcised.

These results were 17 years ago.

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HIV Undetectable Does Equal Uninfectious: The Swiss Statement and the Vindication of Pietro Vernazza

This article was provided by HIV i-Base. It is a part of the publication HIV Treatment Bulletin. Visit HIV i-Base's website to find out more about their activities, publications and services.

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