Postive Nation: Treatment News | Does undetectable mean uninfectious?

Does undetectable mean uninfectious?

Pietro Vernazza, Swiss HIV specialist

A group of Swiss scientists recently said that a person with HIV who’s got a consistently undetectable viral load can’t transmit it. What’s the evidence for this? Are there exceptions? And what might the consequences be? Gus Cairns reports.

On 30 January this year, a group of Swiss HIV specialists released a controversial statement. It said, as part of the public health policy of the Swiss Federal AIDS Commission (CFS): “People with HIV who are not suffering from a sexually transmitted infection and who are on fully suppressive antiretroviral therapy do not transmit the virus through sexual contact.”

Note the wording. Not “have little chance of transmitting the virus.” Not “the evidence suggests that…” No, it was “do not transmit”, in French ne transmettent pas.

In German it was sind nicht infektiös: are not infectious.

The authors qualified their statement carefully. They added that “This statement is valid if:

1 the person is compliant with antiretroviral therapy, whose effect must be evaluated regularly by the treating physician
2 their viral load has been suppressed (non-detectable) for at least six months, and
3 has no other sexually transmitted diseases.”
One of the paper’s authors, Pietro Vernazza, underlines this.
He told Positive Nation: “Our statement was not that there was no risk: we state that the risk of HIV transmission under a list of additional conditions is very low, lower than one in 100,000.
“We also do not say that people should now have sex without condom in such a situation: what we say is that doctors should discuss this with their patients and that this knowledge should be openly discussed together with the patient’s steady partner.
“We felt that every person is free to judge for him/herself how to deal with this information. Some will continue to use condoms. But some will not use condoms in such a situation, and in the case of the Swiss HIV patient cohort, that’s about 15 to 20 per cent.
“We feel that it is not the job of a governmental body to tell people what to do. We want to give our patients and their steady partners the information they need to make their own judgements.”
But it wasn’t the qualifications or careful hedging people reacted to. It was the pronouncement, sanctioned by three of the top HIV doctors in Switzerland, and ratified by the President of the Swiss equivalent of BHIVA, that a large proportion of people with HIV (at least those lucky enough to be living in countries with treatment) could from now on consider themselves no danger
to anyone.
And this was the Swiss saying it! Hardly a nation noted for recklessness.

Why say it now?
One of the report’s authors, Dr Bernard Hirschel of Geneva University Hospital, had, as he put it “flew a balloon,” or tested the waters, by giving an interview to the Geneva local paper two months before,
30 November.

He told Le Temps de Geneve: “We can start…telling treated patients that they are not a public danger. Having a serious disease that one can transmit to others is a heavy burden to carry.”

I catch up with Hirschel at the Retrovirus Conference in Boston in February, and remind him that I talked to him briefly ten years previously, when he was chair of the Geneva World AIDS Conference…so this is not some firebrand young radical of
HIV research.

Hirschel starts by saying that the impulse to say publicly what some doctors have been telling their patients privately for years came initially from witnessing the injustice of people being prosecuted for spreading HIV.

“There have been several trials in Switzerland where people have been sentenced to jail for exposing their partners to HIV. In the last two cases, this was without any HIV infection occurring.” (In the UK there has to be HIV transmission for a criminal offence to have occurred but in Switzerland and a lot of other countries, just endangering someone is enough to get you prosecuted.)

“The defence lawyers said that their clients thought they were uninfectious because they were undetectable. But in the absence of any official documents backing this up, this was inadmissible evidence.”

Secondly, he says, he has also been worried that some people get so worried about HIV “they exchange an imaginary risk for a real one.”

For instance, he says, “many pos/neg couples take extraordinary steps to avoid HIV if they want children. This includes artificial insemination, which means stimulating the woman with hormones to induce ovulation. If she’s the one with HIV that can be risky.
“Another situation is where someone runs to the hospital for post-exposure prophylaxis (PEP) because of sex with an HIV-positive partner. If that partner is undetectable, we estimate their chances of infecting someone as lower than one in 100,000. At these odds, you’d kill a few people with the drugs before saving one from HIV.”

Finally, he adds: “there’s a more speculative but bigger-picture argument that points out that no matter how hard you promote condoms, there’s an incompressible proportion of people who don’t use them consistently. We’ve heard at this conference that there may never be a vaccine, and microbicides are only a hope.

“We’re saying that if treatments continue to become simpler and less toxic, they might become our best hope for prevention.”

(How many people might this apply to at present, by the way? A lot, in countries like the UK. According to the Health Protection Agency, of the 52,000 people receiving HIV care in the UK, two-thirds are on combination therapy and over three-quarters of these are undetectable. So over half of all people diagnosed with HIV in the UK are on ARVs and undetectable, about 27,000 people all told.)

The reaction
What’s the reaction been to the statement, especially among people with HIV?
“The majority of people I’ve talked to think it’s a good thing. I’ve been especially struck by the sense of relief expressed by some African women who’ve felt dirty and ‘contaminated’.”

Some HIV activists second this view. Alessandra Cerioli of the Italian HIV organisation LILA said: “I don’t have a simple opinion on this, but I understand and like the Swiss pragmatic approach. I think it’s good when science and real life are close.”

Swiss activist David Haerry, former Chair of the European Community Advisory Board, said: “My country has a history of condemning & jailing HIV-positives for attempted reckless transmission of HIV. Now the statement is out, this policy cannot be maintained by the courts any longer.”

However some activists and HIV researchers reacted very differently, with criticism, hostility – and even fear. People criticised the new statement as liable to misinterpretation, and even thought it was dangerous. What if people saw it as a licence to go out and have sex without condoms? Would this ultimately result in more infections and a worse public image for people with HIV than the one we already have?

The Terrence Higgins Trust commented: “We’ve known for some time that successful treatment and a low viral load does reduce the risk, but there are still gaps in the scientific evidence, and we can’t say with certainty that HIV won’t ever be passed on in the situation the
Swiss describe.

Hirschel sighs: “If organisations ‘have known for a long time that successful treatment does reduce the risk’, why have they not said so?

“There’s always been this tendency to give ‘maximalist’ prevention messages, meaning ultra-cautious, always use a condom, you can never rule out infection, and so on. Then at least if people don’t respect the message, the individual and not the organisation is to blame.

“The scientific evidence will forever be incomplete, because one cannot prove the absence of a risk”

The evidence
Hirschel is probably right when he says that prevention messages are more often designed to safeguard the committee that wrote them than give realistic information to the individual. However some experts feel the Swiss Statement is on shakier ground when it comes to the actual evidence.

Simon Collins of UK treatment advocates HIV i-Base says: “The transmission risk study that they cite first is...the Rakai study from Uganda. This was a study of about 400 sero-different heterosexual couples where no cases of transmission were seen when viral load in the HIV positive partner was less that about 1500.

“I’m not aware of any similar study in gay men and don’t think these results would be seen in a study of male-male sex. One of the most important and under-reported issues involve viral load levels in the anal tissue.”

This is the contention of other experts too. Where’s all the evidence, they ask? The Swiss statement is based on a slim collection of studies of transmission largely in heterosexuals in long-term relationships.
These have shown, variously, that there is no record of transmission from people with viral loads under 1500, in a group of couples trying to have a baby, and from mums with low viral loads to their babies.
It’s much less clear what happens in situations of casual sex, if people do get an STI, in anal sex, and if people have poor adherence to their HIV treatment.

Sean Hosein of Canadian HIV organisation CATIE says: “In the real world, people have affairs (and don’t tell their partners), STIs can be transmitted (and are often symptom-free), viral load can go up and down, people forget to take their medicines, and so on.”

A large meta-review of studies was recently done by US prevention advocate Seth Kalichman. It found that, while HIV treatment certainly did reduce viral load in semen as well as in blood, the correlation was often not perfect, and in a few cases viral load in the semen persisted for several months after it was suppressed in the blood.

However may studies were done in mixtures of people on and off treatment, in people new to treatment, and on old-fashioned regimes. Kalichman also admits that the study that showed the strongest association between HIV treatment and no virus in semen, which was done by Pietro Vernazza, was the one that most carefully excluded patients diagnosed with an STI. This paper found that no more than 4% of people with an undetectable viral load in blood – and no STIs – would have detectable virus in semen, and
probably fewer.

Another of the few studies done of the effect of STIs on patients on HIV treatment was done by the UK’s Tariq Sadiq and Steve Taylor.

Steve Taylor says: “If you’re undetectable in blood there’s a very high probability of undetectability in the semen. But there are cases where you have detectable HIV in the semen and not in the blood”.

Taylor’s study compared gay men with and without STI-related urethritis (inflammation of the urethra).

It found that in men without urethritis there was a perfect correlation between viral load in blood (under 500) and in semen (under 1000, because semen viral load tests are less sensitive). If their treatment was successful at suppressing HIV in blood, it did so in semen too; if it wasn’t successful and there was HIV in the blood, it was present in most semen samples too (though not all, and at lower levels).

In gay men with urethritis, all the men on unsuccessful HIV treatment with virus in their blood also had it in their semen – but in this case, their semen contained up to 100 times more HIV than the men without an STI.

But all but one of the men on successful treatment, with no HIV detectable in their blood, also had none in their semen.

However: There was one patient who had no detectable HIV in blood but a low-but-detectable viral load – about 2000 – in his semen.

After he got antibiotics for his STI, his semen viral load became undetectable too.

The problem with this, as with a lot of such studies, is one of low numbers. This kind of study is expensive and they only compared 24 men with STIs with 16 men without. So that’s a one-in-24 chance that if you have an STI – which might have no symptoms – you could have virus in your semen even if you’re undetectable.

Taylor adds: “In the case of women, the discordance between female genital tract viremia and blood viremia is far greater.” In other words, the link between undetectability in blood and in genitals is not as strong in women as it is between blood and semen in men. And in women STIs are more often symptom-free.

He concludes: “The Swiss may well turn out to be right, but I feel their evidence is not yet strong to call it fact, and I think there’s a danger of that being misunderstood.”

Conclusions
The debate will probably rumble on for a long time, and all involved agree we need more studies of viral load and infectiousness in people on treatment, especially gay men, people who have casual sex, and above all in people who get STIs.

In the meantime it would seem to be wise to pay a great deal attention to the three very important Ifs in the Swiss statement before you or your partner considers ditching the condoms. Do make sure you take your pills; do make sure you’ve had an undetectable viral load for at least six months or three measurements (or, if you’re negative, that you’re damn sure your partner has); and, above all, make sure you and your partners don’t have STIs.

Which, come to think of it, is another very good reason for sticking to condoms…