Gus Cairns looks at new research on this controversial subject.
The impact of HIV treatment on infectiousness has been a hotly debated topic in recent years. It’s now nearly three years since several Swiss doctors upset the HIV prevention applecart by writing a paper that said that, under carefully stipulated conditions - viral load under 50 copies/ml for at least six months, no sexually transmitted infections, 100% adherence to HIV therapy - a person on antiretroviral drugs was essentially unable to transmit HIV sexually.1
Far from settling the issue, the ‘Swiss statement’ stirred up huge amounts of argument in the HIV prevention community. Everyone agrees people on successful HIV therapy are probably quite a lot less infectious than people not on treatment. But are they uninfectious enough to mean it’s worth taking the risk of not using condoms? The past month has seen the publication of several new studies which, unfortunately, muddy the waters on this particular issue rather than clarify them.
The Swiss doctors based their findings on research involving heterosexual couples that showed there were no HIV transmissions when viral load was below a certain level. This is because HIV treatment reduces the amount of virus in body fluids, including genital fluids.
But there are concerns that even people who have an undetectable viral load in their blood may not always have an undetectable viral load in their genital fluids. A number of studies have shown this in men – and an even higher proportion in women.
Now researchers believe they have identified the main reasons why this can happen.2
Their study involved women starting HIV treatment. The researchers monitored viral load in blood, cervical fluids and vaginal secretions for six months.
Treatment reduced viral load in the blood and genital fluids. The researchers also found that the level of viral load in the blood tended to predict viral load in these genital fluids.
At the end of the study, after taking treatment for six months, 69 women had an undetectable viral load in their blood, but viral load was still detectable in the cervical fluids of 10% of these women and in the vaginal secretions of 32%.
So far, this is what other studies have found. But there’s never really been an explanation as to why some women maintained a viral load in their genitals when they haven’t got one in their veins. One theory was that it was to do with low-level, asymptomatic infection with sexually transmitted viruses like HSV-2 (herpes) and the genital wart virus HPV (human papillomavirus). Others thought it was just constitutional – some people were just, to use a delightful phrase coined by the researchers, “super-shedders” when it came to producing HIV.
This study found a much simpler, and more easily fixed, explanation: the single most important factor associated with a detectable viral load in genital fluids was poor adherence to treatment. When we say ‘poor’, it was actually very good: on average, the women forgot only one in a hundred doses. Nonetheless, the women who didn’t do quite so well on adherence were considerably more likely to have a detectable viral load in their genital fluids than ones whose adherence was perfect.
On the one hand, this means that when the Swiss statement specified 100% adherence to ensure non-infectiousness it really meant it, which may be a tall order for anyone. On the other hand, it does mean there may be a simple and relatively fixable explanation as to why some people are more infectious than others.
The evidence about the impact of treatment on the risk of HIV transmission largely comes from big randomised controlled studies. For instance, a study in Africa last year found that the chances of HIV being passed on between partners was reduced by 92% - better than the average reduction due to attempted consistent condom use – if the HIV-positive partner was on treatment.3 That’s a big treatment bonus.
People enrolled in these trials generally receive a lot of support and good medical care. Often this is at a higher level than is available from routine medical services.
However, ‘real-world’ evidence from the US and Canada has suggested that high rates of treatment within the community may be starting to help prevent new infections.
However, Chinese researchers also looked at this question recently, and found a result that was completely out of line with this.4 Their research involved 1927 couples where one partner was HIV-positive and the other HIV-negative. These couples were monitored for approximately three years.
The transmission rate in couples where the HIV-positive partner was taking treatment was 5%, compared to a transmission rate of 3% in the other couples. That makes it look as if taking treatment was worse in terms of infectiousness than not taking it, but in statistical terms the 2% difference is within the margin of error, and it essentially means the risk was the same, regardless of treatment. Nonetheless, this is a drastically different result from the African study.
In an editorial that accompanied the study, Myron Cohen, a senior US HIV doctor, said the results of this study should cause those who support the wider use of HIV treatment as a way of controlling the spread of the virus to “pause”.5
But why was the result so wildly out of line? In their own paper, the researchers note that people on treatment who did not switch their regimens were much more likely – nearly three times as likely – to transmit HIV than people who had switched their drug regimens.
Why might this be a clue? Well, the researchers did not provide any information on the viral load of the individuals who transmitted HIV to their partners, about whether they had drug resistance, or about measures to support adherence.
However, they also noted that a previous study of drug resistance in Henan province found that only one third of people with HIV were adherent to their treatment after six months of therapy, and that by this time (from an original figure of 14% with drug-resistant HIV), no less than 63% had drug resistance.6
We can’t tell if the same situation applied in this study. But if adherence is poor and people in this region do have high rates of resistance, perhaps due to a lack of support or treatment education, then failing to switch therapies might mean they are much more likely to have drug-resistant HIV – which they then transmit to their partner – than they are if they move to a new therapy.
Until we get more information, we won’t know if that’s the explanation and, as Dr Cohen says, this gives us pause for thought. However, what this study may be showing us is simply that suboptimal treatment regimens and levels of support produce prevention failure as well as treatment failure.
Most of the evidence on the impact of treatment on infectiousness comes from heterosexuals.
But now researchers have attempted to calculate the HIV transmission risk in stable gay couples where one partner is HIV-negative and the other HIV-positive and taking treatment.7
Using condoms all the time provided the most protection against HIV. The researchers calculated that there was a 1% risk of transmission in these circumstances.
Having unprotected sex within six months of the most recent undetectable viral load, but using condoms at all other times, was associated with a 3% risk of transmission. Never using condoms was associated with a 22% risk of transmission.
The researchers say the key message is that consistent condom use is the best way of protecting one’s partner. They also say that the most crucial time to use condoms is when more than three months have gone by since the last undetectable viral load result.
So there you are. HIV treatment will reduce your viral load if it’s successful, and if that happens, you are probably less infectious. But what these studies seem to suggest collectively is that there are an awful lot of ifs and buts to add to that statement and it might not be time to throw away the condoms quite yet.
1. Vernazza P et al. Les personnes séropositives ne souffrant d’aucune autre MST et suivant un traitment antirétroviral efficace ne transmettent pas le VIH par voie sexuelle. Bulletin des médecins suisses 89 (5), 2008.
2. Graham SM et al. Antiretroviral adherence and development of resistance are strongest predictors of genital HIV-1 shedding among women initiating treatment. J Infect Dis 202: advance online publication, DOI: 10.1086/655790, 2010.
3. Donnell D et al. ART and risk of heterosexual HIV-1 transmission in HIV-1 serodiscordant African couples: a multinational prospective study. 17th Conference on Retroviruses and Opportunistic Infections, San Francisco, abstract 136, 2010.
4. Wany L et al. HIV transmission among serodiscordant couples: a retrospective study of former plasma donors in Henan, China. J Acquir Immune Defic Syndr, 55: 232-38, 2010.
5. Cohen MS HIV treatment as prevention: to be or not to be? J Acquir Immune Defic Syndr, 55, 137-8, 2010.
6. Li JY et al. Prevalence and evolution of drug resistance HIV-1 variants in Henan, China. Cell Res 5(11-12):843-9, 2005.
7. Hallett TB et al. Estimating the risk of HIV transmission from homosexual men receiving treatment to their HIV-uninfected partners. Sex Transm Infect, July 2010.
