Approximately 65% of the high risk EXPLORE cohort met our criteria for inclusion in either subcohort and among these, serosorting and seropositioning were both reported by a sizable minority. By definition, the seropositioning and serosorting cohorts comprise men who report both HIV-uninfected and HIV positive/unknown anal intercourse partners, as well as inconsistent condom use and/or role versatility, and are thus behaviorally at higher risk for HIV. For almost half of the serosorting subcohort, the odds of using a condom with HIV-infected or unknown status partners were at least twice that with partners believed to be HIV-uninfected.
Other studies in HIV-uninfected MSM in multiple areas including a Seattle STD clinic 
a cross-sectional survey in Atlanta 
and a cohort study in Australia
have defined serosorting as reporting unprotected anal intercourse only with partners believed to be HIV uninfected and found prevalences of this strategy of 26–38%. The prevalence of serosorting in our study is not directly comparable, because we focused on a subgroup of high-risk men who reported both HIV positive/unknown and HIV negative partners and both protected and unprotected anal intercourse. However, this did allow us to evaluate preferential condom use by partner type within a participant, which may identify those that intentionally utilized serososorting as a harm reduction strategy. We found that seropositioning was reported relatively less commonly than serosorting in EXPLORE, as was also seen in the Australian cohort
. However, nearly half of the participants in our analyses did not practice either serosorting or seropositioning, as shown by scores of ≤1.
To our knowledge, this is the first evaluation to utilize multivariable modeling to examine the effect of seroadaptation strategies on HIV incidence in a large prospective cohort of HIV-uninfected MSM whose reported behaviors place them among those at highest risk for HIV infection. Our finding that increasing serosorting was independently associated with a modest decrease in risk for HIV infection was encouraging, particularly since this protective effect was evident even among men with greater numbers of partners, which has been shown to be a independent risk factor for HIV infection in EXPLORE as well as another MSM cohort study
Furthermore, in previous studies, both serosorting and strategic positioning have been associated with an intermediate risk of HIV seroconversion when compared to no unprotected anal intercourse (lowest risk) and unprotected receptive anal intercourse with an HIV-infected partner (highest risk)
. Certainly, seroconversion has also been reported despite serosorting in case control studies
and surveys of MSM
. Modeling studies have also suggested that attempts at serosorting could paradoxically increase risk for HIV infection, particularly in the setting of acute HIV, a stage of disease which is suspected to be highly infectious due to high viral loads, but during which conventional HIV antibody tests are negative
In contrast to our findings, there are several reasons why we might have expected an increased risk of HIV infection associated with serosorting or seroadaptation in this study. For one, many men are unaware of their HIV infection status, and also may make assumptions about a partner's HIV status
. Additionally, as shown in a recent study of over 1800 HIV infected MSM, even for those who are aware of their own status, disclosure to sex partners can be complex and fraught with difficulty
. It is possible that the regular frequency of HIV testing, the enhanced participant-centered counseling that was provided to all EXPLORE participants or our inclusion criteria for these analyses contributed to our findings.
In addition to issues of generalizabilty, the study did have some additional limitations. Assessments of seropositioning and serosorting relied on participant report, which could have been subject to desirability bias despite attempts to minimize this by utilizing computer assisted self-survey. We were also unable to directly assess participant intention to practice seropositioning and serosorting as risk reduction strategies, although our study design did allow for measurement of the magnitude of these behaviors; neither could we evaluate differences in reported behavior with regular versus casual partners. Our findings could be biased by unmeasured confounders, including time-dependent factors such as knowledge of partner status. In addition our findings cannot be extended to MSM who are monogamous, do not practice anal intercourse, or who have only HIV-negative or HIV positive or unknown status partners. Finally, we measured only two specific seroadaptation behaviors out of the many that exist, including some which were reported by EXPLORE participants, and so cannot speak to the efficacy of those other practices.
Despite concerns that serosorting may contribute to unacceptable risk of HIV infection in MSM
, our findings were that it did not increase risk and was even associated with a small protective effect. However, given this small magnitude of effect, counseling and health messages should continue to emphasize condom use and reducing numbers of partners as the mainstays of individual prevention efforts. Our findings, along with other studies, suggest that serosorting may have a role as a harm reduction strategy for MSM who currently practice unprotected anal intercourse with partners without serosorting. However there is currently no evidence to suggest that serosorting is as safe as consistent condom use and limiting numbers of partners.
Further qualitative studies could evaluate intention and skills associated with MSM who practice these behaviors, and also whether there are potentially modifiable factors that could be used to encourage and support serosorting as a harm reduction approach for MSM who do not always use condoms.
Although using condoms consistently and limiting numbers of partners remain central to HIV prevention, those MSM who choose serosorting as harm reduction should also be supported in this currently practiced, community-originated strategy. First, since disclosure is the keystone of any seroadaptation strategy, efforts to decrease barriers and routinize frequent HIV testing among MSM must be a continued priority of public health. However, since frequent testing alone may be insufficient due to limitations of antibody testing during acute HIV infection and the increased risk of HIV transmission associated with this period
, improved tests, including pooled RNA testing and more sensitive fourth generation EIA, should become widely available to improve diagnostic accuracy of HIV testing for those at high risk of infection including MSM. Furthermore, additional research into interventions that encourage and support disclosure to partners is also necessary to maximize any potential HIV prevention benefit of serosorting as a harm reduction strategy.