It should be noted that although these trials were disappointing in terms of the impact on HIV of the behavioural interventions that were evaluated, some trials showed an impact on other sexual and reproductive health outcomes. The most important of these are noted in Table 2. For example, the MkV Trial showed significant improvements in sexual and reproductive health knowledge, reported attitudes, and some, but not all, reported sexual behaviours both in the follow-up conducted about 3 years after the start of the interventions and after more than 8 years. However, it did not demonstrate any consistent impact on herpes simplex virus 2 (HSV2) or other STIs. On the contrary, the Stepping Stones Trial showed a statistically significant decrease in HSV2 of one-third, and the Masaka Trial also reported a borderline significant reduction in HSV2.
Interpretation and potential explanations
There are three main potential reasons for these disappointing findings: the interventions tested were inherently ineffective, they were inadequately implemented, or there were problems with the measurement of effectiveness. It is clear that at least two of the studies suffered from inadequate implementation. In the Masaka Trial, some aspects of the in-school intervention, including the teaching on condoms, were not delivered in the majority of schools, at least partly because the teachers were expected to teach the classes outside normal school hours . A different problem affected the Regai Dzive Shiri Trial, in which it appears that the interventions per se were both well designed and well implemented. However, the original intention was to evaluate the effectiveness of the interventions in a cohort of young people recruited at baseline and then particularly targeted for the interventions. However, an interim follow-up survey after about 2 years showed that attrition from the cohort was likely to be unacceptably high, so the design was changed to a cross-sectional survey of all young people living around the centre of the intervention community. This meant that the primary trial outcome had to change from HIV incidence to HIV prevalence, but, more importantly, subsequent analysis showed that the exposure to the various components of the intervention had been rather low in the evaluation group (Cowan et al. 2008, Table 1). Any analysis restricting to those with adequate exposure might introduce bias and would negate the advantages of the randomized design. These two examples demonstrate that large behavioural intervention trials face important challenges wherein the realities of intervention and evaluation implementation can sometimes lead to compromises. Such trials necessarily tend towards the evaluation of effectiveness rather than efficacy.
It should also be remembered that none of the trials evaluated the intervention in a vacuum. HIV prevention efforts have been in place in all countries since the early stages of the epidemic, though of varying natures and intensities, so all participants in both arms of the trial will have been exposed to some other HIV prevention interventions. In some trials (e.g. Stepping Stones, VCT, SHAZ, EXPLORE, and Mexico), these were further reinforced in the comparison arm by additional HIV prevention interventions, though either of a different intensity or approach to those in the intervention arm. Behaviour change interventions may take several years to have a major impact. Also, their effect may not be linear. There may even be a tipping point before which there is very little impact and after which there is a major impact. Yet, most of these trials have evaluated impact at one or a limited number of points in time, usually with follow-up being limited to 2–3 years .
Despite these important caveats, it is clear that the results of these trials of behavioural interventions are not encouraging in terms of their effectiveness against HIV. However, we know that true behaviour change (such as always using a condom with a discordant partner) would reduce HIV incidence. Also, population-level changes in behaviours have been associated with reductions and increases in HIV incidence in observational studies (such as in Uganda ). The problem appears to be two-fold. First, it is likely that none of the behavioural interventions that have been tested to date within large-scale trials with HIV as an outcome have had a substantial enough impact on HIV risk behaviours. But also, several of the trials that have been performed have either suffered from problems with intervention implementation, coverage, or have been underpowered to be able to detect a realistic effect size on HIV.
In general, trials that evaluated behaviour change against behavioural outcomes have had more encouraging results than those using HIV or other biological outcomes . Yet, it is essential that, if interventions are to recommended because of their effectiveness for HIV prevention, then trials must include HIV and, wherever possible, other biological outcomes such as other STIs and pregnancy. Trials with reported sexual behaviours as their outcome are insufficient for three main reasons:
- Because of the limited validity of reported sexual behaviour, particularly in young people [24–26]. In some settings, immaculate conceptions appear to be a common event when reported sexual behaviours are validated against biological markers of pregnancy, and many sexually transmitted infections would have had to have been acquired nonsexually .
- Because social desirability bias in reporting of sexual risk behaviour is likely to be greater at follow-up in the intervention arm. For example, if one has been telling people in the intervention arm that they should use a condom each time they have sex, they are more likely to misreport having used a condom at follow-up than those in the comparison arm.
- Because the incidence or prevalence of other STIs, let alone reported sexual behaviours, may not be good surrogates for HIV .
The way forward: research
Despite the discouraging results of the trials reviewed above in terms of the impact of the behavioural interventions evaluated against HIV, effective ways of preventing HIV and STIs are urgently needed, and research to develop and evaluate such interventions should remain a high priority, including research on potential behavioural interventions. Several of these trials and others, which did not measure HIV as an outcome , have shown that, at the least, such interventions can increase knowledge on HIV, its modes of transmission, and methods of prevention, and can impart the skills needed to change behaviours such as negotiation of safe sex and sexual refusal skills.
Future trials to evaluate the effectiveness of behavioural interventions should have HIV as an outcome and be realistically powered to be able to detect a difference of 25% in HIV incidence, allowing for the fact that HIV incidence may well be lower in the comparison arm that predicted by preliminary studies. This means that they will need to be both large and expensive. This has not proved to be an insurmountable problem for funders of trials of biomedical interventions such as HIV vaccines, microbicides, and male circumcision; behavioural trialists must convince funders that their trials are of similar importance and merit adequate funding with long enough follow-up to produce reasonably unequivocal results. They must also include detailed process evaluation and collect data on secondary outcomes on the theoretical pathway by which the behavioural intervention is thought to have its effects on HIV. Very careful thought needs to be given to the choice of what will be done in the comparison arm of the trial. If this is excessive, then the chance of the trial being able to show a significant difference will be reduced.
Although such RCTs will continue to have an important place, especially if large enough and with long enough follow-up, intervention research should not be limited to trials. Studies of processes of change that aim to advance knowledge of the mechanisms by which interventions may work to change behavioural risk-taking, and which attempt to identify key mediators of behaviour change will also be important .
In terms of the interventions themselves, particular attention needs to be given to the social and sexual norms of the general population among whom the particular target group (such as young people or groups most at risk) live and interact. For young people, this should include the people who either control or influence their behaviours such as their parents and other adult relatives, older role models and influential people in the community, and external influences such as radio, films, television, and songs.
Also, most interventions evaluated to date have targeted HIV acquisition among the HIV-uninfected individuals; equal attention needs to be given to evaluating interventions that focus on prevention of HIV transmission from HIV-infected individuals. As discussed above, interventions to reduce HIV acquisition will need to target young people, and then be maintained thereafter, whereas interventions to reduce HIV transmission will need to primarily target young and middle-aged adults rather than adolescents. The latter will include interventions to reduce their number of sexual partners, and particularly their concurrent partners, and to increase their use of condoms even within long-term relationships. It will also be important to evaluate multicomponent behavioural interventions that target both HIV acquisition and HIV transmission.
Research is also needed on how the more widespread availability of HAART and antiretroviral therapy (ART) for prevention of mother-to-child transmission (PMTCT) affects the effectiveness of behavioural interventions among HIV-positive adults and discordant couples to reduce HIV transmission, and hence how best to design these interventions. Changing access to HAART will also complicate evaluations that use HIV prevalence as an outcome, as effective HAART programmes will lead to increasing HIV prevalence as HIV-related mortality declines, unless this is coupled with reductions in HIV incidence due to reduced viral load in those on treatment.
For technical reasons, mass media approaches have not been evaluated within the RCTs reviewed above. Yet this does not mean that they cannot be evaluated, at least in terms of their impact on knowledge, report attitudes, and reported self-efficacy, using carefully designed before-after studies .
Another area needing further research is the impact of HTC on HIV incidence, given the worrying findings from the Zimbabwean trial (VCT) described above and the results from many other studies in Africa and elsewhere which have shown that although reported sexual risk-taking tended to be reduced after VCT among those who tested HIV-positive, it tended to either be unchanged or was increased in those who tested HIV-negative [31–33]. A recent meta-analysis  of seven intervention studies (most of which were before–after or time series studies) of the impact of VCT on condom use and/or reported number of partners reached more encouraging conclusions, but data on the individual studies included in the meta-analysis again shows that although risk behaviours were more likely to decrease after VCT among those who tested HIV-positive or among discordant couples who tested together, the results were not clear cut among those who tested HIV-negative . Could it be that HTC is good for persuading HIV-positive individuals to reduce their risk of onward transmission of HIV to their partners, but leads to relative disinhibition among those who test HIV-negative along the lines of ‘I have taken risks in the past and have not been infected, so maybe I can continue with my previous behaviours’? But perhaps it is also that the posttest counselling for those who test HIV-negative is often too perfunctory or is not heard by the client who has just been told that they are HIV-negative?
Finally, we need to explore the potential for alternative study designs to the RCT with HIV as the primary outcome, exploiting the potential for careful plausibility evaluations within ‘natural experiments’ when programmes are being started, and continuing the search for cheaper but valid surrogate markers of HIV. Although RCTs will remain the most rigorous and convincing intervention study design, they are not always feasible either technically (e.g. to evaluate mass media interventions) or because of funding, and other study designs have a potential contribution to make as long as they are carefully designed to try to rule out extraneous reasons for the effects observed, and their limitations are acknowledged .
The way forward: programmes
Given the burden of the HIV epidemic in high-prevalence countries, decisions about the implementation of programmes, including interventions that aim to reduce behavioural risks of HIV, will not wait for further research results to become available.
In the meantime, programmes should continue to promote in-school interventions to increase the knowledge and skills of young people, not because they are likely to have a direct impact on HIV incidence in the short-to-medium term, but as a long-term investment as they will help to provide the background level of knowledge and may influence the general population attitudes related to sexual risk and HIV. Similarly, interventions to improve the quality of the sexual and reproductive health services provided by health facilities and to increase their utilization by clients deserve continued support, as they have been shown to be capable of success at least in terms of these limited outcomes .
Condom uptake remains pitifully low in most countries, especially those with high HIV prevalence . Much more strenuous efforts need to be made to both promote their use and to make them ubiquitously available.
Although the importance of concurrent partnerships is widely acknowledged, interventions that aim to specifically target this pattern of sexual relationship are still largely in their infancy, and their introduction should be linked to careful evaluation.
It is widely acknowledged that HIV prevention is likely to require multiple strategies, leading to calls for ‘combination prevention’ approaches. These are discussed in detail in the paper by Hankins and de Zalduondo in this issue .
Finally, although this article has focused exclusively on interventions that solely or largely rely on the promotion of low-risk sexual behaviours among the population at risk of either HIV acquisition or HIV transmission, it is important to realize that biomedical and structural interventions will also require behaviour change. For example, for male circumcision, a biomedical intervention, to be successful in prevention of HIV, men will need to come to health services to request the procedure, to abstain from sex for a period of several weeks after the operation, and then not to risk compensate by either increasing their number of sexual partners or reducing their condom use, for example. Similarly, ARTs for the PMTCT of HIV prevention will require high adherence to the medications by the clients.
This paper draws heavily on a literature review that was reported by Judy Wasserheit at the ISSTDR Conference in London in June 2009. It also draws on discussions with my colleagues in the Mwanza NIMR/LSHTM Research Team and collaborators over many years, and discussions held at the Mwanza Intervention Trials Unit (MITU) Scientific Symposium in Mwanza in July 2009.
This paper is dedicated to the people of Mwanza Region who have participated in the many HIV prevention research studies that have taken place over the past 20 years, and which have advanced our knowledge on what works, or, all too often, what does not work in terms of interventions to reduce behavioural HIV risk.
David Ross is a staff member of the London School of Hygiene and Tropical Medicine. No specific external funding was used to support the preparation of this paper, though his attendance at the MITU Symposium was supported by the MkV Trial Long-term Evaluation Project funded by the UK Department for International Development and Irish Aid. (Irish Aid is the name of the Irish Government's Aid Agency.)
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Keywords:© 2010 Lippincott Williams & Wilkins, Inc.
effectiveness; HIV; interventions; prevention; sexual behaviour