Types of studies
The review will include randomised controlled trials (RCTs), in which participants were allocated to intervention conditions either individually or by cluster, and non-randomised controlled studies in which observations were made in all groups before and after intervention implementation. Included studies will be limited to those in which a combination HIV prevention intervention was compared against a control group receiving a different HIV prevention intervention (including both single-component and other combination interventions), standard care, or no intervention.
We recognise that the exclusion of less rigorous non-randomised studies (e.g., single-group before-and-after studies) will probably result in the de facto exclusion of a subset of intervention evaluations, particularly those containing structural components, in which the use of control groups was considered not feasible, ethical and/or necessary by the study authors. Given the growing consensus that, in principle, no defining characteristic of structural interventions precludes the use of comparison groups or random allocation in their evaluation (Bonell 2006; Hayes 2010), evidenced in part by the multiple RCTs of combination prevention interventions containing structural components that have been conducted (e.g., Pronyk 2006) or are presently underway (e.g., Vermund 2013), it was determined that requiring included studies to employ comparison groups was reasonable.
Types of participants
Studies specifically targeting MSM, irrespective of age, language, geographic location, ethnicity, or any other sociodemographic indicator, will be included. For the purposes of this review, ‘MSM’ refers to a behavioural category inclusive of all biological males who have sex with biological males, regardless of their sexual or gender identity. MSM encompasses, for example, transgender women, male sex workers, straight-identified MSM, gay and bisexual men, and MSM who identify with a number of other culturally specific sexual and gender identities.
It bears mentioning that the term ‘MSM’, which was coined in the 1990s with the intention of reducing stigma against gay, bisexual, transgender and straight-identified men who have sex with other men, oversimplifies the array of sexual behaviours in which men engage, sacrificing specificity of behaviour in favour of the sensitive inclusion of all biological males who have sex with biological males. The term also fails to differentiate between the variety of sexual and gender identities, and social and behavioural characteristics thereof, represented in populations of ‘homosexually active’ men (Young 2005). While the importance of understanding the social and behavioural diversity of MSM is appreciated, the term ‘MSM’ continues to be widely used in the literature and, in the interest of standardisation across studies, its use was deemed necessary in this review.
If non-MSM participants are included in a study, we will obtain outcome data for the subset of MSM included.
Types of interventions
Any HIV prevention intervention containing at least two of the three major categories of intervention component (biomedical, behavioural and structural) will be eligible for inclusion. For the purposes of this review, components will be defined as below, based largely on the descriptions and representative examples provided in the UNAIDS Discussion Paper on combination HIV prevention (UNAIDS 2010). In order to be classified as biomedical, behavioural and/or structural, an intervention must explicitly aim to reduce HIV transmission risk according to the means described in the definitions below.
Biomedical interventions are those that reduce exposure to, transmission of, or infection with HIV, either by providing a physical barrier between the virus and susceptible tissue or by creating a physiological environment in or on the body that is hostile to viral replication and/or survival. Examples include: condom provision, medical male circumcision, oral pre- and post-exposure prophylaxis, rectal microbicides, antiretroviral ‘treatment as prevention’, and biomedical STI treatment services.
Behavioural interventions are strategies that promote individual behaviour change to reduce the risk of HIV transmission (though they need not be delivered at the individual level). While the categorisation of most behavioural intervention components is uncontroversial, some could arguably be classified as biomedical interventions. HIV testing, for example, is often justifiably considered a biomedical intervention because of its provision by medical practitioners and its effect as a gateway to engagement with medical services for those who test positive. However, for the purposes of this review we will consider HIV testing a behavioural intervention component because the well established preventive effects associated with the receipt of a positive test result (Crepaz 2009; Denison 2008; Marks 2005) operate primarily through behaviour change resulting from knowledge of positive serostatus. Other examples of behavioural interventions include: individual and group counselling, behaviour change communication (including gay venue-based risk reduction and condom promotion), educational interventions targeting MSM, peer education and persuasion, community development and/or mobilisation programs aiming to alter predictors of HIV risk within the gay community (and/or MSM network), and prevention commodity (e.g., condom) social marketing (e.g., via posters and billboards) targeting MSM.
Structural interventions are defined, for the purposes of this review, as interventions that aim to alter environmental or societal-level factors beyond the gay community (and/or MSM network) that may affect vulnerability to HIV infection or that may dilute the effectiveness of other HIV prevention interventions. These factors include, inter alia, population-wide accessibility of prophylactic technologies (Blankenship 2000); HIV/AIDS-related stigma among healthcare practitioners and policy-makers and in the general population (Valdiserri 2002); society-wide gay/MSM-related stigma (i.e., homophobia), which acts as a barrier to health service and prophylactic access for MSM (Fay 2011; Santos 2013) and, through the production of internalised homophobia among individual MSM (Berg 2013), can increase HIV-related risk behaviours like substance abuse (Shoptaw 2009) and unprotected anal sex (DeLonga 2011; Ross 2008; Ross 2013); and the presence of discriminatory policies, including those that criminalise consensual homosexual sexual activity (Beyrer 2011; Itaborahy 2013) and that outlaw or accord lesser status to same-sex domestic partnerships (Klausner 2006). While structural interventions may ultimately result in behaviour change, they are distinguished from behavioural interventions by the targeting of the contextual factors beyond the gay community/MSM network, that nonetheless affect individual or group behaviour, rather than the behaviours themselves (Gupta 2008). For example, while a behavioural intervention may aim to directly change risky behaviour by providing sexual health education to MSM and encouraging them to engage with health services, seek testing, and disclose their HIV/STI status to partners, a structural intervention may aim to decrease homophobia and HIV-related stigma among healthcare providers, creating ‘safe spaces’ the for testing and monitoring of STIs in the MSM population, thus facilitating risk reduction behaviour. Still, some intervention components could arguably be classified either as structural or behavioural interventions. Community development and/or mobilisation programs, for example, may be considered structural interventions because they often work by addressing population- and society-wide determinants of HIV risk like homophobia. The definition of structural interventions that will be used in this review is largely consistent with this classification. However, many community development and/or mobilisation interventions aim specifically to decrease risky sexual behaviour among MSM by changing community norms within the gay (or MSM) community, rather than the population at large. As noted above, this subset of interventions will be categorised as behavioural interventions for the purposes of this review unless it is clear that the community development/mobilisation is primarily geared towards campaigns that are structural in orientation. Examples of structural interventions include: large-scale community development programs, community mobilisation and dialogue programs, and educational media interventions that address determinants of HIV risk operating beyond the MSM population; stigma reduction programs and anti-homophobia campaigns targeted at the general population, policy makers, healthcare providers, or other practitioners or leaders; policy and legal reform; and broad-based programmes designed to improve access to health and HIV prevention services, including prophylactic technologies, across the general population.
Many condom-based prevention interventions, particularly those that both provide and promote the use of condoms, are likely to qualify both as biomedical and behavioural interventions. The distinction between these two types of component deserves elaboration. For an intervention to fulfil the classification criteria for any component category, it must both explicitly aim to reduce HIV transmission risk through the means described in the relevant definitions above and, if applicable, provide the material features of the intervention modality thought to be required to achieve risk reduction. The features involved in condom promotion interventions (behavioural) may include, for example, educational materials, posters, or counselling sessions, while those involved in condom provision (biomedical) are, at minimum, the condoms themselves. A condom promotion intervention that does not involve condom provision would be classified as a single-component behavioural intervention, while a condom provision program implemented without a substantive behavioural condom promotion component would be classified as a single-component biomedical intervention. A combination behavioural-biomedical condom promotion and provision intervention would therefore need to explicitly include the behavioural and biomedical intervention features (i.e., respectively, condom promotion materials or activities, and condoms) required to reduce HIV transmission risk in accordance with the above criteria. It is worth noting that large-scale condom distribution interventions are often classified as structural interventions (Charania 2011), particularly when their aims include the improvement of the accessibility, acceptability and/or availability of condoms (Blankenship 2000). While interventions involving only the distribution of condoms to MSM will be defined as single-component biomedical interventions in this review, those that combine widespread condom distribution with additional components addressing population-wide condom accessibility, acceptability, and/or availability (i.e., structural-level mediators of HIV vulnerability) will be categorised as combination biomedical-structural interventions.
Because of potential disagreement about the definitions of intervention categories, the description of intervention components by study authors as biomedical, behavioural or structural will not be used to categorise interventions for the purposes of this review. Rather, we will examine the content of interventions as described in study reports (or via communication with authors, as needed) to classify intervention components and categorise interventions according to the above criteria.
We anticipate considerable heterogeneity between studies on the basis of the different combinations of intervention components that are evaluated. As discussed below in the ‘Data synthesis’ section we will analyse pooled study results in subgroups on the basis of the presence of different types of intervention component and combinations thereof.
Types of outcome measures
To be eligible for inclusion in the review a study must have assessed at least one of the outcomes listed below. Biological outcomes (especially HIV incidence) are the most accurate indicators of the success of HIV prevention interventions. However, given that only one behavioural intervention trial (Koblin 2004) and no known evaluations of structural interventions for MSM have included HIV incidence as an endpoint, and that many interventions are designed to reduce HIV transmission risk among MSM who are living with HIV (for whom HIV incidence is an irrelevant outcome), it is useful and necessary to record several relevant sexual behaviour outcomes. It may also be informative to record any structural-level pathway variables targeted by interventions, though ex ante determination of these variables is problematic because their relevance as predictors of HIV vulnerability tends to vary depending on the context and the presence of other factors, and evidential support for hypothesised pathways between putative structural factors and HIV risk is limited (Auerbach 2011). Nonetheless, in addition to biological and behavioural outcomes, we will collect data on the broad categories of structural factors thought to be associated with HIV risk that are listed below.
When outcome data are reported at multiple follow-up points, data from the latest endpoint will be recorded in order to capture sustained intervention effects.
Incidence of HIV
Incidence of other STIs
Number of occasions of unprotected anal intercourse (UAI) during recall period
Proportion of participants reporting at least one occasion of UAI during recall period
Number of partners for UAI during recall period
Number of occasions of unprotected receptive anal intercourse (URAI) during recall period
Proportion of participants reporting at least one occasion of URAI during recall period
Number of partners for URAI during recall period
Number of occasions of unprotected insertive anal intercourse (UIAI) during recall period
Proportion of participants reporting at least one occasion of UIAI during recall period
Number of partners for UIAI during recall period
Number of occasions of UAI with serodiscordant partner(s) and/or partner(s) of unknown serostatus during recall period
Proportion of participants reporting at least one occasion of UAI with serodiscordant partner(s) and/or partner(s) of unknown serostatus during recall period
Number of serodiscordant partners and/or partners of unknown serostatus for UAI during recall period
Indicators of societal homophobia and/or anti-MSM stigma, including tolerance of and attitudes towards homosexuality reported by decision-makers, healthcare providers, and members of the general population; frequency of reported anti-gay physical and verbal abuse and human rights violations; and introduction of punitive anti-gay laws and policies
Indicators of societal HIV/AIDS-related stigma, including tolerance of and attitudes toward people living with HIV (PLHIV) reported by decision-makers, healthcare providers, and members of the general population; frequency of reported physical and verbal abuse against PLHIV and HIV-related human rights violations; and introduction of coercive or discriminatory legislation against PLHIV
Indicators of the successful enforcement of laws and implementation of policies protecting MSM or PLHIV rights or preventing MSM- or HIV/AIDS-related discrimination
Potential society-wide economic mediators of HIV risk, including income per capita, economic inequality metrics (e.g., Gini coefficient), and affordability of housing and other basic needs
Indicators of the society-wide accessibility and uptake of health services including HIV prevention programming, HIV counselling and testing, STI prevention and treatment services, and HIV prophylactic technologies
Educational indicators, including societal-wide educational attainment, and levels of HIV/AIDS- and sexual health-related knowledge