AJPH PREEXPOSURE PROPHYLAXIS

Individual Versus Community-Level Compensation Following Preexposure Prophylaxis of HIV

We analyzed the concept of risk Martin Holt, PhD, and Dean A. Murphy, PhD compensation and how it has been applied in HIV prevention, See also Landers and Kapadia, p. 1534. to consider the impact of PrEP on paying particular attention to community norms and practices the strategy of HIV preexposure and not only on the immediate reexposure prophylaxis and safety and recalibrate their prophylaxis (PrEP). In risk com- recipients of the intervention. P (PrEP) is one of the most actions if they perceive that pensation, reduced perceptions Risk compensation theory significant developments in HIV they are exceeding their target of risk after the introduction relies on a rational actor model prevention, providing an al- or acceptable level of risk. A of a preventative intervention of human behavior, which is ternative and supplement to pre- key part of risk compensation derived from classic economic lead to more frequent risk- vention methods such as theory is that the benefits of an theory and has not been without taking behavior. Such a change . PrEP involves intervention (e.g., seatbelts) can its critics.9,10 The idea that risk may undermine the interven- HIV-negative people regularly be outweighed over time as compensation is inevitable is tion’sprotectivebenefits. taking antiretroviral drugs to people begin to feel safer and contested, particularly when We found that many studies prevent HIV infection.1,2 It has then increase their risk-taking highly effective interventions purporting to investigate risk been found to be highly effective behavior (e.g., driving faster or are introduced. Also, it is not in preventing HIV acquisition more dangerously). The theory compensation do not assess or straightforward to measure contends that an intervention report changes in perceptions of in multiple population groups, people’stargetlevelsofrisk, may fail unless the target or ac- risk, instead relying on behavioral particularly gay and bisexual men, making the theory difficult to ceptable level of risk is reduced, measures. Our analysis suggests as long as recipients regularly take test. Because of the variability that is, unless people are moti- a complex and sometimes coun- the prescribed drugs (at least in findings (in safety and 3 vated, educated, or incentivized terintuitive relationship between four doses per week). However, other areas), researchers suggest the development of PrEP has to behave more prudently. the introduction of a new pre- that more attention needs to not been without controversy. vention intervention, perceptions be paid to the conditions under Before the efficacy of PrEP was of HIV risk, and subsequent which risk compensation does demonstrated, researchers were and does not occur. changes in behavior. already concerned that “PrEP RISK COMPENSATION As PrEP is introduced, we be- may be used as a justification for We considered how risk lieve comprehensive assessment of increasing the frequency or types compensation has been used in community-level risk compen- of risk-taking behaviors, which the HIV field, particularly in sation—that is, changes in risk could result in higher rates of relation to PrEP. We discuss RISK COMPENSATION perceptions and behavior as sexually transmitted infections the theory of risk compensation AND HIV a result of increased optimism and fuel HIV transmission.”4(p864) and how it has been measured. Risk compensation has gar- about avoiding HIV among The concept of increased risk We suggest alternative ways to nered attention as a way to un- people not directly protected by taking undermining the effective- assess the impact of PrEP, in- derstand why the uptake of “ PrEP—should not be omitted. ness of an intervention is often cluding evaluating prevention HIV prevention measures “ optimism.” We argue that re- sometimes fail to achieve a re- We therefore suggest ways to referred to as risk compensa- ”5,6 searchers and evaluators need duction in HIV infections assess prevention optimism tion, and the implementation of PrEP has intensified debates and community-level risk com- about it. ABOUT THE AUTHORS pensation. (AmJPublicHealth. Risk compensation is a con- Martin Holt and Dean A. Murphy are with the Centre for Social Research in Health, 2017;107:1568–1571. doi:10.2105/ University of New South Wales, Sydney, Australia. Dean A. Murphy is also with the cept derived from risk homeo- Department of Gender and Cultural Studies, University of Sydney, Australia. AJPH.2017.303930) 7,8 stasis theory. It suggests that Correspondence should be sent to Martin Holt, Centre for Social Research in Health, Level 2, people continually evaluate the John Goodsell Building, UNSW Sydney, NSW 2052, Australia (e-mail: [email protected]. fi au). Reprints can be ordered at http://www.ajph.org by clicking the “Reprints” link. potential and bene ts of This article was accepted May 16, 2017. their actions for their health doi: 10.2105/AJPH.2017.303930

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and as something to monitor when randomized trials in Africa have PREEXPOSURE which is higher than in the introducing new interventions.5,6 foundlittleevidencethatmed- PROPHYLAXIS AND placebo-controlled phase.1 A It has been investigated in relation ical male leads to RISK COMPENSATION large, open-label trial in the to condoms, HIV treatment, male increased sexual activity or more United Kingdom found that 15,16 PrEP researchers were cog- circumcision, and PrEP as well condomless sex. nizant of the potential for risk PrEP reduced the risk of HIV as potential future strategies (e.g., Fourth, changes in behavior fi infection by 86% among gay and compensation, and the rst large 22 microbicides and vaccines). IfHIV may be rendered irrelevant be- randomized controlled trials bisexual men and that after one interventions lead to a reduced cause a prevention strategy is so year PrEP users were more likely monitored the sexual behavior perception of risk and subsequent effective that there is little chance than were nonusers to report of participants over time.1,2,4 adoption of compensatory be- of increased HIV transmission, recent, receptive condomless sex The trials did not focus on per- havior such as more sexual partners despite changes in perceived risk (21% vs 12%). ceptions of risk (as participants or more acts of condomless or sexual behavior. For example, In these open-label studies, did not officially know whether sex, then risk compensation is studies have found that adopting changes in behavior did not di- they were receiving PrEP or considered to have occurred. use may precede people minish the efficacy of PrEP in a placebo). The first completed There are several observa- having more partners or engaging preventing HIV infection. In- studies found that the combined tions we can draw from previous in more frequent sex, but there creased condomless sex, along drugs tenofovir and emtricitabine research on risk compensation is little evidence that this leads to an with the increased monitoring reduced the risk of HIV infec- andHIV.First,moststudiesrely increased risk of HIV.12 When that PrEP users receive, may, tion by 44% to 75% (modified on behavioral measures (e.g., efficacy is lower, risk compensation however, contribute to the high intention-to-treat analysis), with number of partners or con- may pose a greater problem. The rates of other sexually transmitted higher efficacy among people domless sex), without measur- promotion of male circumcision infections that have been ob- who had detectable drug levels. ing or reporting on attitudinal as a population-level prevention served among PrEP users.23 The studies found no evidence changes or perceptions of strategy, for example, has been However, because PrEP is not risk.11,12 Failing to assess per- controversial because of its of increased condomless sex designed to reduce the risk of fi during the trial period (in fact, ceived risk overlooks a key part moderate ef cacy and lack of 1,2 sexually transmitted infections, of risk compensation theory7,8 protection for female partners.17 condom use increased). A re- increases in sexually transmitted and means that changes in sexual Finally, most research on risk cent systematic review and infections should perhaps be behavior are assumed to be compensation and HIV focuses meta-analysis of 18 trials found considered unintended conse- evidence of risk compensation, on individuals who receive or use that PrEP reduced the risk of HIV quences of PrEP rather than rather than demonstrating that an intervention, rather than infection by 70%, compared with a failure of the HIV-related in- changes in attitudes or percep- considering the effect of in- placebo, as long as participants tervention. How to manage 3 tion precede changes in behavior. terventions on risk perceptions were at least 70% adherent. The sexually transmitted infections as Second, even when attitudes and behavior in the broader review also found no evidence PrEP use increases remains and risk perceptions are mea- community.5 An example of of increased risk-taking behavior a subject of debate. sured, the temporal relationship a compensatory effect occurring in the studies. with behavior may not be clear. beyond those who are the direct To assess risk compensation This relationship is important targets of an intervention is that of related to PrEP, we recommend because some prospective studies HIV treatment optimism: the examining situations outside have found that more frequent belief that it is easier to avoid HIV randomized controlled trials in PREVENTION engagement in condomless sex, (or less serious to contract HIV) as which users know that they are OPTIMISM for example, can precede the a result of effective antiretroviral receiving an active drug that is The effect of PrEP on risk 20 development of optimistic atti- treatment.18,19 People with op- effective in preventing HIV. perceptions and sexual practices tudes about avoiding HIV.13 timistic beliefs about avoiding The open-label extension of at a community level has not Third, studies of risk com- HIV because of treatment have the international iPrEx (Iniciativa been systematically assessed. In pensation and HIV sometimes been found to be nearly twice as Profilaxis Preexposicion or San Francisco, California, one show no change in behavior, likely to report condomless sex as Prexposure Prophylaxis Initia- of the first locations to embrace or even change in a counterin- are their more skeptical peers, tive) study found that, after PrEP, an analysis by Chen et al. tuitive direction. For example, regardless of their HIV status.14 a year’s follow-up, PrEP users of behavioral surveillance in- a meta-analysis found that This finding suggests that it is were slightly more likely than dicates that consistent condom HIV-positive people in treat- important to assess how the in- were nonusers to report receptive use by HIV-negative gay and ment or with an undetectable troduction of a new intervention condomless sex (25% vs 20%), bisexual men (including men viralloadwerenomorelikely (like PrEP) affects risk percep- whereas other behaviors not using PrEP) has declined to engage in condomless sex tions and sexual behavior at a remained unchanged.21 The more rapidly since PrEP was than were other people living community level, not just among level of HIV risk reduction ob- introduced.24 The authors sug- with HIV,14 whereas large those receiving the intervention. served in the study was 51%, gest that some men “have given

October 2017, Vol 107, No. 10 AJPH Holt and Murphy Peer Reviewed Commentary 1569 AJPH PREEXPOSURE PROPHYLAXIS

particularly interested in opti- EXAMPLES OF MEASURES OF HIV PREVENTION OPTIMISM RELATED TO PrEP mism and condomless sex among people not using PrEP, that is, Item Measured Aspects of Prevention Optimism community-level risk compen- a ’ How likely do you think it is that you will become HIV positive? Individual s perceived risk of HIV infection sation. This is because current Because of PrEP, I am less likely to get HIV.b Personal optimism research suggests limited changes It is safe for me to have sex without condoms if I am using PrEP.b Personal optimism, direct protection in behavior and, when behavior It is safe for me to have sex without condoms if my partners are Personal optimism, direct protection does change, little overall impact fi using PrEP.b on ef cacy in preventing HIV among PrEP users. Of more rel- It is safe for me to have sex without condoms because other people Personal optimism, indirect protection evance, in our opinion, is in- are using PrEP.b creased risk taking by people Sex without condoms has become safer because of PrEP. Community-level optimism unprotected (or not directly pro- Because of PrEP, fewer people will get infected with HIV.b Community-level optimism tected) by PrEP that is driven by The availability of PrEP makes condom use less important.b Community-level optimism unrealistic optimism (particularly As more people use PrEP, condom use becomes less important.b Community-level optimism in situations in which HIV in- fection rates are sustained or in- Note. PrEP = preexposure prophylaxis. creasing). For example, over the a Score from very unlikely to very likely (5-point scale). past 20 years, rates of condomless bScore from strongly disagree to strongly agree (5-point scale). sex and HIV infection rates have gradually increased among gay and bisexual men in many 25 up consistent condom use under a suggested list of measures to in San Francisco it may be realistic high-income countries. If the assumption that other men assess prevention optimism in the (and not optimistic) to believe prevention optimism leads to will be using PrEP.”24(p2794) box on this page. condomless sex has become safer, increases in condomless sex AlthoughtheuptakeofPrEP Optimistic attitudes could because HIV infections have among those not using PrEP, can be tracked using behavioral develop at a community level and continued to decline since PrEP’s thiscouldtemperornegatethe fi surveillance, it is difficult to subsequently affect practice introduction.24 population-level bene ts of determine whether changes in through contact with PrEP users However, in other settings, PrEP use. To assess changes in percep- behavior are a result of risk (as sexual partners, friends, or HIV incidence among gay and tions of risk, the development compensation without assessing peers) or through learning about bisexual men is stable or in- of prevention optimism, and attitudes to PrEP and the per- PrEP through media and word of creasing,25 and PrEP use is rare, so community-level risk compen- ceived risk of acquiring HIV. mouth. Both of these mecha- it would be optimistic to rely on sation, we recommend that The cross-sectional nature of nisms could lead to a belief that PrEP use by others and believe measures such as those in the box most behavioral surveillance also PrEP is effective and that the risk that condomless sex is safer. We on the previous page be included meansthatitisnotpossibletosee of condomless sex has been re- think this belief in indirect pro- in repeated surveys (including if changes in attitudes lead to duced because of PrEP. tection as a result of PrEP and behavioral surveillance) and changes in behavior (or vice It is critical to distinguish be- a premature reduction in con- prospective cohort studies. Re- versa). We are therefore advo- tween condomless sex with (or dom use regardless of local peated, cross-sectional studies can cating cross-sectional and pro- among) people using PrEP (di- epidemic conditions best assess community-level changes spective research on what we call rect protection) and condomless encapsulates the idea of pre- in attitudes and behavior over “ ” prevention optimism. sex with people not using PrEP vention optimism. In this way, time, although they cannot assess We derived the concept of because of the belief that con- prevention optimism departs whether changes in attitudes prevention optimism from pre- domless sex has become safer in theoretically from risk compen- precede changes in behavior at vious work on HIV treatment general through the increased use sation because it encompasses the individual level. Longitudinal 14,18,19 fi optimism. We de ne of PrEP in the population (in- a more diffuse effect at a com- cohort studies could assess prevention optimism as the belief direct protection). Believing that munity level that could impede whether prevention optimism that it is easier to avoid HIV in- PrEP use by others makes con- the population effectiveness of leads to risk compensation (and fection or transmission because domless sex safer may be partic- PrEP rather than solely focusing increased risk of HIV) among of PrEP and that it is more ac- ularly inaccurate (and risky) in on the behavior of individuals or both PrEP users and nonusers, ceptable and safer to engage in contexts where HIV infections dyads using PrEP. if they monitor participants’ condomless sex because the risk have not declined after PrEP’s Prevention optimism could be perceptions of risk, beliefs of HIV is perceived to be re- introduction or where there is assessed in PrEP trials, as has been about PrEP, sexual behavior, duced. We have included limited use of PrEP. For example, suggested by others,20 but we are and HIV incidence.

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Qualitative research could people unprotected by PrEP. We developments in psychology and sociol- 23. Kojima N, Davey DJ, Klausner JD. – explore and contextualize believe it is important to identify ogy. Risk Anal. 2006;26(2):397 411. Pre-exposure prophylaxis for HIV in- 11. Gray RH, Kigozi G, Kong X, et al. fection and new sexually transmitted in- changes in risk perception and this to respond to unintended and fections among men who have sex with The effectiveness of male circumcision for – sexual behavior among PrEP unwanted changes in perception HIV prevention and effects on risk be- men. AIDS. 2016;30(14):2251 2252. nonusers, especially if interview and practice, if they occur, and haviors in a post-trial follow up study in 24. Chen YH, Snowden JM, McFarland participants are followed over increase the likelihood of cur- Rakai, Uganda. AIDS. 2012;26(5):609– W, Raymond HF. Pre-exposure pro- 615. phylaxis (PrEP) use, seroadaptation, and time. When attempting to as- tailing or eliminating the sexual sexual behavior among men who have sex 12. Pinkerton SD. Sexual risk com- with men, San Francisco, 2004–2014. certain the degree of community- transmission of HIV. pensation and HIV/STD transmission: AIDS Behav. 2016;20(12):2791–2797. level risk compensation owing empirical evidence and theoretical CONTRIBUTORS to PrEP and prevention opti- considerations. Risk Anal. 2001;21(4): 25. Sullivan PS, Hamouda O, Delpech V, M. Holt wrote the first draft of the 727–736. et al. Reemergence of the HIV epidemic mism, we recommend also assessing commentary. Both authors developed the among men who have sex with men in 13. Huebner DM, Rebchook GM, concept for and refined and revised the North America, Western Europe, and attitudes to HIV treatment and Kegeles SM. A longitudinal study of the 18,19 commentary, and agreed on the final Australia, 1996–2005. Ann Epidemiol. treatment optimism so that association between treatment optimism submitted version. 2009;19(6):423–431. there is a chance to disentangle and sexual risk behavior in young adult gay fi the effects of different biomedical and bisexual men. J Acquir Immune De c ACKNOWLEDGMENTS Syndr. 2004;37(4):1514–1519. prevention strategies on percep- The Centre for Social Research in Health 14. Crepaz N, Hart TA, Marks G. Highly receives funding from the Australian tions of risk, behavior, and risk of active antiretroviral therapy and sexual risk Government Department of Health. behavior: a meta-analytic review. JAMA. HIV. We are not aware of any Both authors declare nonfinancial 2004;292(2):224–236. such studies, and we encourage support from Gilead Sciences, Inc., outside our colleagues to consider them. the submitted work. 15. Bailey RC, Moses S, Parker CB, et al. Male circumcision for HIV prevention in REFERENCES young men in Kisumu, Kenya: a rando- mised controlled trial. 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