A large study looking at HIV infections in gay men who are within long-term relationships with HIV-positive partners is about to start in Australia, the International Microbicides Conference in Sydney heard today.
This Opposites Attract study will look at the risk of HIV acquisition by the HIV-negative parter within different-status relationships and hopes to make an estimate of the comparative risks of HIV transmission from HIV-positive partners who are, and are not, on antiretroviral therapy (ART). Initially starting in Sydney, Melbourne, Brisbane and Adelaide, it is planned that the study will expand to other Australian cities and to Thailand.
Calculations of study size and expected loss to follow-up are being informed by findings from a large study of HIV risk in gay male relationships, the HIM study (Bavinton).
Background
The need for a study of HIV transmission risk and the influence of viral suppression in gay men has existed ever since the Swiss Statement in 2008. This said that within certain parameters people with an undetectable viral load could not sexually transmit HIV, but the authors later emphasised that evidence for this was only strong in studies of vaginal sex. The need for further evidence became stronger when the HPTN 052 study found that treating the HIV-positive partner in heterosexual different-status relationships reduced their chance of transmitting HIV by 96%. Since then both the British HIV Association and the US Department for Health and Human Services have recommended ART for prevention purposes in some patients, but both emphasise that the assumption that this will work for gay men is an extrapolation of the data for heterosexuals, and another study recently found that up to a quarter of gay men with no detectable HIV in their blood may have detectable levels in semen.
A study looking at whether treatment works as prevention is thus badly needed in gay men. While a randomised controlled study of immediate versus delayed treatment like HPTN 052 will be difficult to do in the future, given changes in the criteria of ART initiation, an observational study of risk within different-status relationships could be done. The challenge, however, will be that gay male relationships are less likely to be monogamous, and HIV more likely to be transmitted during casual sex, than in heterosexuals. A study was therefore undertaken of different-status and same-status gay male relationships to assess whether a transmission study would be feasible.
The HIM Study findings
The Health in Men (HIM) study is a cohort of 1427 initially HIV-negative gay men recruited in 2001 to 2004 to look at risk factors for HIV, which has provided useful data on risk behaviours in other studies.
In this study, an analysis was done of data originally collected in 2007. HIM subjects completed annual interviews and were asked whether they were in a primary relationship, how long it had lasted, whether their partner had HIV and, if so, whether the subject knew their viral load. Characteristics of different-status and same-status relationships were collected.
Two-thirds of HIM subjects reported being in a primary relationship of which 8.4% (79 individuals) reported that their partner had HIV. This is roughly the same as the proportion of gay men estimated to have HIV in New South Wales (see Prestage). Another 21% of the subjects, however, reported that they did not know their partner's HIV status.
Within the 79 different-status partnerships, two-thirds of HIV-negative men knew their partner's HIV viral load, and 58% said it was undetectable.
In terms of contrast between different-status and same-status relationships, some factors were similar, such as age of the HIM subject and their partner, the length of the relationship (roughly 50% had lasted longer than two years) and whether sex was permitted with people outside the relationship.
The rate of relationship breakup was similar too: each year, 29% of different-status relationships and 26% of same-status relationships broke up. Different-status relationships were less likely to break up if they had been going for more than two years, if the HIM subject was over 44, and if the relationship involved 'serospositioning' (i.e. the HIV-negative partner was only ever 'top' if they had sex without a condom).
Other things were different, though. HIM subjects in different-status relationships were more likely than other subjects to report having sex outside the relationship, having unprotected sex with casual partners, and having tested for HIV in the last three months, and were 2.5 times more likely to report that they were in an open relationship.
Conversely, they were less likely to report having unprotected sex within the relationship, to have 'negotiated safety' agreements about no condomless sex outside the relationship, and to be the receptive partner.
There were eight new HIV infections in the 79 men in different-status relationships during the average 3.9 years of follow-up. HIV incidence among men in different-status relationships was 2.2% a year and 0.7% in same-status relationships (hazard ratio: 3.12). HIV acquisition was three times more likely if the HIM subject had been 'bottom' with their partner in unprotected sex, and over 15 times more likely if their partner had ejaculated inside them. HIV transmission was six times more likely to occur within the first year of a relationship than after that point and was 4.7 times more likely if the HIM subject was under 35 than if they were over 44.
Conclusions
Presenter Benjamin Bavinton said that these findings posed challenges for the designers of the forthcoming Opposites Attract study. Firstly, the high break-up rate meant that recruitment had to be ongoing throughout the relationship in order to replace attrition due to break-ups. Secondly, high rates of sex outside the primary relationship meant that phylogenetic testing of all HIV infections was essential to establish which were transmissions from the primary partner (results would not be released to participants). Thirdly, Australian criminal law meant that sexual risk behaviour data could only be collected from HIV-negative participants. Fourthly, because infection was so much more common in the first year of relationships, men in new, tentative and not necessarily committed relationships would have to be recruited. And finally, most of the blood tests would have to be done with the initially HIV-negative partner, including when the relationship might have just broken up or just after they had received the news that they had acquired HIV: retention in these circumstances might be a big problem.
Nonetheless, recruitment is about to start: for would-be subjects and professionals interested in the study, there is more information at www.oppositesattract.net.au.
Bavinton B et al. Exploring gay men’s serodiscordant relationships: Implications for future ‘treatment as prevention’ studies in gay men. InternationalMicrobicides Conference, Sydney, 2012. See here for programme.
Prestage G et al. Homosexual men in Australia: population, distribution and HIV prevalence. Sexual Health 5(2):97–102, 2008.