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An undetectable history – Investigating undetectable HIV: 1981 – today

By Chris Williams, updated 3 years ago in Health / Sexual health

Red HIV AIDS ribbon around finger

We now know the use of antiretroviral treatment by someone living with HIV helps them to reach an undetectable viral load – and being undetectable is an extremely effective HIV prevention strategy. So how long have we known about the importance of being undetectable to prevent onward transmission of HIV and what does this mean for the future?

Introduction

June 2021 marks the 40 year anniversary of the first report from the US Centers for Disease Control and Prevention (CDC) of what would later be known to the world as HIV.

Since the arrival of zidovudine (AZT) in 1987 – the first effective antiretroviral medicine – biomedical technologies have advanced in leaps and bounds. From around March 1996, HAART (highly active antiretroviral therapy) became the new standard for treating HIV using a combination of different classes of HIV medicines.

This approach can reduce HIV viral load levels to undetectable and protect the health of the immune system against the development of potentially fatal diseases. As a result, millions of lives have been, and continue to be saved every day.

“The power of treatment as prevention cannot be underestimated in helping to achieve global targets to dramatically reduce new infections and improve the health of those already living with HIV.”

Most people living with HIV and using regular treatment will reach an undetectable viral load. However, a very small number of people may not achieve this. Even in this small number of cases, the virus may still be suppressed to very low levels which will result in a greatly reduced risk of onward HIV transmission to sexual partners compared to not being on treatment at all.

The past: 1981 – 2016

5 June 1981 – Recognising the start of the epidemic

The first AIDS-related deaths were reported in the United States by the CDC. This news marked the first official reporting of what would become known as the HIV/AIDS epidemic. 36 years later there are now almost 37 million people living with HIV globally.

30 March 2000 – Rakai project study group, Uganda

In a community-based study of more than 15,000 people in Uganda, many mixed HIV status couples were followed as part of a behavioural study into HIV transmission. Groundbreaking for the millennium, the study concluded that viral load is the chief predictor of the risk of heterosexual transmission of HIV, and transmission is rare from people with levels less than 1,500 copies/ml.

Although this study didn’t focus on sexual behaviours of same-sex attracted men, it is perhaps one of the earliest conclusions from a large scale study of what we now know to be true about the benefits of reducing viral load.

30 January 2008 – The Swiss statement

While Switzerland is known for its long term neutrality on foreign policy, in 2008 a statement issued originally in French and German by the Eidgenössische Kommission für Aids-Fragen (EKAF) – the Swiss Federal Commission for AIDS-related Issues – resulted in a commotion of international proportions.

It all came about because HIV positive people in Switzerland were being criminalised if they had sex with HIV negative partners, even if both people consented. Creating this statement was especially important to help heterosexual mixed HIV status couples to have children naturally without facing legal charges.

The translated statement noted: “An HIV-infected person on antiretroviral therapy with completely suppressed viraemia (“effective ART”) is not sexually infectious, i.e. cannot transmit HIV through sexual contact.” It went on to say that the statement was valid as long as three conditions were met:

  • The person adheres to antiretroviral therapy, the effects of which must be evaluated regularly by the treating physician; and
  • The viral load has been suppressed below the limits of detection (i.e. below 40 copies/ml) for at least six months; and
  • There are no other sexually transmitted infections (STIs).

HIV sector reactions to the statement came from much farther afield and with more aggression than was anticipated by the Swiss. Curiously, the two main types of criticism seemed to contradict each other: One stance maintained that while the statement was considered to be true, it should not be made public due to fears of risk compensation – a gay abandon of condoms – something which was feared would end up increasing transmission of HIV and other STIs. The second stance argued that the risk of HIV transmission from having sex with a partner with suppressed viral load was not negligible (with a specific focus on anal sex). For anyone following the rise of PrEP over the past few years in Australia, perhaps there’s a sense of history being repeated?

Is it ethical to withhold information from the public due to fear that the epidemic might worsen as a result of informing them? Eight years after releasing the Swiss statement, Swiss Medical Weekly published an update titled HIV is not transmitted under fully suppressive therapy: The Swiss Statement – eight years later to deliver a fascinating insight into this question and more.

19 July 2011 – HPTN 052 proves HIV treatment is prevention

By 2011 scientists, doctors, and others had suspected for quite a while that a person on effective antiretroviral treatment with an undetectable viral load would be significantly less likely to infect a sexual partner. The results of a landmark randomised, controlled trial named HPTN 052 proved that early antiretroviral therapy can indeed prevent onward HIV transmission.

HPTN 052’s interim results found there was a whopping 96% reduction in HIV transmission for people starting immediate antiretroviral therapy compared to those who delayed starting treatment. This was perhaps the most significant research to date on HIV treatment as prevention presented at the 6th International AIDS Society Conference on HIV Pathogenesis, Treatment and Prevention (IAS 2011). Reports from the conference soon made a stir online as well: IAS 2011: The Proof is Here: HIV Treatment is HIV Prevention

While numbers less than 100% might sound like cause for concern, it’s important to note the reason HPTN 052 reported a 96% risk reduction (based on the study’s interim results) and a 93% risk reduction (based on the study’s final results) is because transmissions occurred before treatment had the chance to suppress the virus to levels that would provide protection, and also due to the fact that treatment did not suppress the virus in a very small number of the participants. If only transmissions after the first six months of treatment had been considered, the risk reduction would have been 100% with a transmission risk of zero!

In 2013 following the interim results of the HPTN 052 study, the World Health Organization recommended that antiretroviral treatment be offered to all people living with HIV who have HIV negative partners to reduce HIV transmission.

4 March 2014 – PARTNER Study (First Phase)

Despite results from the earlier study HPTN 052 yielding significant evidence for HIV transmission reduction in heterosexuals, the question of undetectable viral load and transmission risk related to gay men and anal sex was still unanswered. The PARTNER study was designed to remedy this gap in knowledge. By March 2014 it had recruited 1110 mixed HIV status couples, with nearly 40% of them being gay couples.

Reported at the 21st Conference on Retroviruses and Opportunistic Infections (CROI 2014), the main news from the first phase of the study was that from an estimated 16,400 acts of condomless gay sex and 14,000 acts of condomless heterosexual sex, there had been no HIV transmissions from a partner with an undetectable viral load – Zero!

What’s also interesting is that no transmissions occurred despite quite high levels of STIs, especially among the gay couples participating. In 2008 the Swiss statement declared that people with an undetectable viral load did not transmit HIV, but it made an exception when it came to the presence of an STI. This early announcement from the PARTNER study might be the first indications that STIs (in either the positive or negative partner) don’t increase the likelihood of HIV transmission if the positive partner is on treatment and undetectable.

23 February 2015 – ACON says ‘Drop Your Load’ to communicate the concept of UVL

Meanwhile, through the Ending HIV campaign, New South Wales based LGBTI health organisation ACON sent a message with a cheeky slogan to promote the health benefits of having an undetectable viral load. This was the first campaign of its time that spoke to the entire community about this new science regardless of sero-status. The campaign followed ACONs position statement released at the AIDS 2014 conference: UVL = Safe Sex.

While previous messaging had focused on the health benefits for people living with HIV, the ‘Drop Your Load’ slogan communicated the concept of undetectable viral load as a means for HIV negative guys to prevent HIV transmission.

13 July 2016 – Terrence Higgins Trust in the UK comments on PARTNER study final results

PARTNER continued monitoring the condomless sex lives of participating heterosexual and gay couples to complete the intended duration of the study. As it turned out there were no cases of within-couple HIV transmission… and they’d sure been working hard for science — couples were estimated to have had sex 58,000 times without condoms during the study period!

Dr Michael Brady, Medical Director at Terrence Higgins Trust in the UK, said: “We can now say with confidence that if you are taking HIV medication as prescribed, and have had an undetectable viral load for over six months, you cannot pass HIV onto your partner, with or without a condom. The risk is effectively zero.”

The results from PARTNER provided the strongest estimate of actual risk of HIV transmission when an HIV positive person has an undetectable viral load – and that risk is effectively zero.

“We can now say with confidence that if you are taking HIV medication as prescribed, and have had an undetectable viral load for over six months, you cannot pass HIV onto your partner, with or without a condom. The risk is effectively zero.”

PARTNER’s significance was to reverse a common assumption that some level of risk must always exist when enjoying condomless sex with someone living with HIV who has an undetectable viral load. The academic question it raised is whether the risk of HIV transmission is anything other than merely theoretical when someone is managing an undetectable viral load through effective treatment. The study did its job to provide strong evidence. What was needed next was resounding and unwavering support from people in authority.

1 December 2016 – NIH Statement on World AIDS Day 2016

World AIDS Day in 2016 marked 35 years of the epidemic, and more than 35 million deaths. Reflecting on remarkable achievements in biomedical science and public health, The National Institutes of Health (NIH) – the primary agency of the United States government responsible for biomedical and public health research – issued a statement.

One powerfully worded excerpt reads: “Antiretroviral therapy has been transformational for both individuals and communities. Large studies conducted in diverse settings, from U.S. cities to African villages, have demonstrated the power of treatment to preserve the health of those living with HIV. Additionally, studies have proven that when an individual living with HIV is on antiretroviral therapy and the virus is durably suppressed, the risk that he or she will sexually transmit the virus is negligible. Research also has repeatedly demonstrated that HIV incidence diminishes when HIV testing is aggressively implemented, individuals with HIV infection are linked to treatment, and support is provided to keep them in care. The power of treatment as prevention cannot be underestimated in helping to achieve global targets to dramatically reduce new infections and improve the health of those already living with HIV.”

“…studies have proven that when an individual living with HIV is on antiretroviral therapy and the virus is durably suppressed, the risk that he or she will sexually transmit the virus is negligible.”

With reputable agencies like the NIH getting on board, the importance and validity of the common message about the many benefits of becoming undetectable through effective HIV treatment are undeniable.

The present: 2017

9 February 2017 – NAM endorses U=U consensus statement

Of course, it’s always nice when other leading experts agree and endorse the message too. NAM aidsmap is one of the foremost sources of HIV information in the world. In a post that strongly endorses the ‘Undetectable Equals Untransmittable’ (U=U) Consensus Statement issued by the Prevention Access Campaign, NAM’s Executive Director, Matthew Hodson, said “The scientific evidence is clear. Someone who has undetectable levels of virus in their blood does not pose an infection risk to their sexual partners.” He goes on to say, “In terms of HIV prevention, if condom use is safer sex, then sex with someone who has maintained an undetectable viral load is even safer sex.”

“In terms of HIV prevention, if condom use is safer sex, then sex with someone who has maintained an undetectable viral load is even safer sex.”

Hodson continues to provide context for what the U=U consensus statement means for many people living with HIV: “Those of us with diagnosed HIV have had to live with the idea that our bodies are dangerous. This has had a profound emotional impact on many people. Many people who live with the virus face not just sexual but also social rejection as a result. In some countries having sex without disclosing HIV status is criminalised, regardless of whether there is a risk of transmission. Ignorance about transmission risk means that people are turned away from services, such as tattooists, or even denied medical treatment. No other sexually transmitted infection carries the same power to strike fear into the hearts of the population.”

The full consensus statement is issued by the Prevention Access Campaign, founders of the Undetectable = Untransmittable (U=U) community, which includes and is endorsed by many of Australia’s AIDS councils, peak bodies, other HIV organisations and community groups. As a taste of what they’ve all endorsed, this excerpt sums it up nicely: “There is now evidence-based confirmation that the risk of HIV transmission from a person living with HIV (PLHIV), who is on Antiretroviral Therapy (ART) and has achieved an undetectable viral load in their blood for at least 6 months is negligible to non-existent. (Negligible is defined as: so small or unimportant as to be not worth considering; insignificant.)”

And if you do happen to check out the Prevention Access Campaign’s FAQs, they really do justice to something we’ve thought about a lot – is the risk really zero? Their answer: “In real world terms, yes the risk is zero. In theoretical terms, the risk is a tiny fraction close to zero. The challenge is that scientific studies can never prove the risk is zero. Through statistical analysis that number will keep getting closer and closer to zero. Researchers agree that because the actual HIV transmission risk is either zero or extremely close to zero, a person with HIV with an undetectable viral load is considered ‘not infectious’ to their sexual partners.”

“There is now evidence-based confirmation that the risk of HIV transmission from a person living with HIV (PLHIV), who is on Antiretroviral Therapy (ART) and has achieved an undetectable viral load in their blood for at least 6 months is negligible to non-existent.”

19 June 2017 – Emen8 launches the “Undetectable = Safe” campaign

Emen8 is a new, national initiative for gay men, bisexual men and other men who have sex with men. As an Australian first, Emen8 is designed to make information about HIV and STI prevention engaging… but you probably already knew that if you’re reading this right now.

Besides being self-referential, we also produced Australia’s national sexual health promotion campaign to promote the (not so new?) news that Undetectable = Safe

Undetectable = Safe | Emen8

While some people might think our message is coming a little late to the party, it’s OK – we brought really good drugs… antiretrovirals! And these ones come highly endorsed.

The future: beyond 2017

Having recognised our undetectable history, what seems more important now is our undetectable future. We have evidence showing that Australia and northern European countries are doing far better than North America at retaining people living with HIV in care and achieving viral suppression. In fact, a report from 2014 showed us leading the global HIV response: 86% of people living with HIV were diagnosed, 76% were retained in care, 66% were receiving antiretroviral therapy and 62% had an undetectable viral load.

And we’re improving year on year. National statistics from The Kirby Institute show there were an estimated 25,313 people living with HIV in Australia in 2015. Of these, an estimated 90% were diagnosed by the end of 2015, 85% were retained in care, 75% were receiving antiretroviral therapy, and 69% had an undetectable viral load.

Using treatment to maintain a viral load that falls below thresholds considered to be infectious is one of the most effective HIV prevention strategies available to us. Our future depends on fostering cultural acceptance of this message, and removing any physical or psychological barriers before it. Every single one of us can support people to manage their sexual health, go for tests and maintain regular usage of antiretrovirals.

If the timeline of biomedical HIV prevention were a day, PrEP users are arriving for a late lunch. They’re beginning to learn what it’s like to use antiretroviral medication every day similar to what their HIV positive counterparts have been doing since the crack of dawn. The sero-divide grows smaller through even these similarities – one of us lives with the virus and one of us doesn’t, yet we both now manage HIV through use of antiretrovirals. And there’s a wealth of knowledge and experience people living with HIV can provide.

We’re not sure if it’ll be these common bonds that help us forge even more loving relationships with each other, or whether it’ll be mass acceptance of the knowledge that Undetectable = Safe. Either way, we have the opportunity to increase our understanding, eliminate stigma and help heal a community fractured by an epidemic.

Now that’s a future we can all really look forward to.