Studies highlight complex questions about how communities will respond to PrEP

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Two consecutive sessions at the 19th International AIDS Conference (AIDS 2012) in Washington DC highlighted some of the complexities of translating exciting research findings about pre-exposure prophylaxis (PrEP) into effective large-scale HIV prevention strategies.

In 2010 and 2011, two landmark studies reported that when certain antiretroviral drugs are taken by HIV-negative people at high risk of acquiring HIV, transmission is much less likely to occur. PrEP regimens have been shown to have a protective effect among heterosexuals with HIV-positive partners, as well as among men who have sex with men (MSM). (See Pre-exposure prophylaxis on aidsmap for more information.)

In May 2012, these findings led the US Food and Drug Administration to become the first major regulatory body to approve the prophylactic use of an existing antiretroviral drug, Truvada, by HIV-negative people. Truvada (a combination of tenofovir and FTC) can greatly reduce the likelihood of HIV infection occurring, but it does not by any means provide complete protection against the virus.



An umbrella term for people whose gender identity and/or gender expression differs from the sex they were assigned at birth.

adjusted odds ratio (AOR)

Comparing one group with another, expresses differences in the odds of something happening. An odds ratio above 1 means something is more likely to happen in the group of interest; an odds ratio below 1 means it is less likely to happen. Similar to ‘relative risk’. 


Insertive anal intercourse refers to the act of penetration during anal intercourse. The insertive partner is the ‘top’. 


Receptive anal intercourse refers to the act of being penetrated during anal intercourse. The receptive partner is the ‘bottom’.

Mycobacterium Avium-Intracellulare (MAI)

Infections caused by a micro-organism related to TB which can cause disease in people with advanced HIV.

One concern, therefore, is whether using PrEP as a targeted HIV prevention intervention in high-risk populations may encourage some people who take it to consequently engage in what is known as “risk compensation”, i.e., reducing other important protective practices such as condom use. There are also concerns about affordability, acceptability and willingness to adhere to PrEP regimens. (The small number of biomedical studies reported to date indicate that missing doses can have a major impact on PrEP’s level of effectiveness.)

The World Health Organization is encouraging demonstration projects that will generate the evidence necessary for it to develop public health recommendations regarding PrEP. In a recently released interim guidance document, the agency observed that “while the effects on risk behaviours, values, preferences and resource costs have been studied in conjunction with the clinical trials, they are not well understood in actual application, and so the feasibility of PrEP implementation is not known”.

One study presented at the conference explored the issue of risk compensation by surveying more than 5000 North American men who were members of an internet social network for men who have sex with men (MSM). Survey respondents were asked to hypothesise what their sexual behavior would be if they were taking PrEP. One-fifth of respondents thought that they would decrease condom use for insertive anal sex, and 14% thought that they would do so for receptive anal sex.

Men who reported having unprotected anal sex in the previous three months were more likely than other men to anticipate decreasing their use of condoms for both insertive and receptive anal sex (adjusted odds ratios, respectively, 1.58, 95% confidence interval 1.22-2.04, p = 0.0005; 1.57, 95% CI 1.16-2.13, p = 0.004). Factors that signaled potential drug and alcohol abuse were also associated with anticipated decreases in condom use. An additional factor associated with anticipating less condom use was having a higher self-perceived risk of acquiring HIV.  

Another research team surveyed 89 seronegative partners of HIV-positive people in the US state of South Carolina about risk compensation issues. More than a quarter of respondents predicted that if they were taking PrEP, they would be more likely to have unprotected sex with an HIV-positive partner. A similar proportion thought that they would have difficulty taking PrEP daily and consistently using condoms as well.

Men (56% of the study population) were more likely than women to associate the prospect of taking PrEP with inconsistent condom use with an HIV-positive partner (aOR 10.43, 95% CI 2.67-40.79). MSM (26% of the study population) were less likely than heterosexual respondents to do so (aOR 0.21, 95% CI 0.05-0.87).

As in the study carried out among internet social network members, the South Carolina study called attention to current sexual risk-taking as a factor potentially associated with sexual behavior in the context of PrEP use. The perception “condom is no longer needed while taking PrEP” was more likely among respondents who reported not using condoms during last sexual intercourse (aOR 7.45, 95% CI 1.57-35.45).

In many settings, people who might benefit greatly from PrEP are not necessarily aware of or knowledgeable about this new HIV prevention strategy. Since awareness and knowledge could greatly affect uptake of PrEP, researchers are keen to explore these issues as well.

An Australian PrEP study analysed online survey results from 1041 MSM, 88% of whom were HIV-negative. Researchers sought to assess how well PrEP might be accepted in this population by asking study participants whether they agreed or disagreed with various statements.

Both HIV-positive and HIV-negative respondents were inclined to agree that PrEP is effective for preventing HIV, and also to agree that it is not as effective as condoms. However, HIV-negative respondents differed from HIV-positive respondents in that they did not think taking HIV treatment was straightforward.

In the Australian study, HIV-positive and HIV-negative respondents agreed that use of PrEP “would make people less responsible”, a finding that may add weight to concerns about risk compensation. Meanwhile another study, this one drawing on focus group discussions with US MSM whose HIV status was either HIV-negative or unknown, found that many study participants “were concerned that PrEP could prompt increased sexual risk-taking across the MSM community”.

An encouraging theme to emerge from the two conference sessions was that the concept of PrEP seemed to elicit generally favorable responses across a variety of study populations. A study of MSM in the US cities of Miami (N = 321) and Washington DC (N = 323) found that, even though fairly small proportions of study participants reported already knowing about PrEP, almost half of the Miami cohort and almost two-thirds of the Washington DC cohort indicated willingness to take PrEP.

Among Miami MSM, non-injecting drug use in the past year was associated with being less willing to use PREP – but MSM in Washington DC who reported non-injecting drug use in the past year were more willing to take PrEP.

Another study evaluated attitudes toward PrEP among MSM and male-to-female transgender persons in Chiang Mai, Thailand. This city was one of the sites for the 2010 study that showed a reduction in HIV transmission among MSM taking PrEP.

Perhaps as a result of the earlier biomedical study, the 131 MSM and 107 transgender persons who were surveyed about PrEP had high levels of prior awareness of this intervention. Respondents were asked to rate their likelihood of using PrEP if the efficacy level was 50%, i.e., if PrEP prevented half of all cases of HIV transmission that would happen if PrEP was not used. Three-quarters of MSM and 77% of transgender people indicated that they were either “very likely” or “somewhat likely” to use PrEP.

Factors associated with willingness to use PrEP were not the same for MSM and transgender people. Acceptability was higher among MSM who had a prior history of sexually transmitted infections, and among those who expressed strong confidence in their ability to take daily medications for one year. For transgender study participants, prior awareness of PrEP and having private insurance were significant factors.

Another difference to emerge was that transgender study participants, many of whom were taking female hormones, were more likely to express concern about how PrEP might interact with other medications.

Taken together, the studies presented at the conference indicate the potential for a great deal of variation in how people at high risk of acquiring HIV respond to opportunities to use PrEP, suggesting the need for further research across diverse populations and subpopulations.


Metsch L et al. Willingness to take daily pre-exposure prophylaxis (PrEP) among MSM in two HIV epicenters in the United States. Nineteenth International AIDS Conference, Washington DC, abstract TUPDC0301, 2012.

Tripathi A et al. Perceptions and attitudes about PrEP among seronegative partners and the potential of sexual disinhibition associated with the use of PrEP. Nineteenth International AIDS Conference, Washington DC, abstract TUPDC0302, 2012.

Underhill K et al. Project PrEP Talk: an in-depth qualitative analysis of PrEP acceptability, expectations and risk compensation beliefs among United States MSM. Nineteenth International AIDS Conference, Washington DC, abstract TUPDC0306, 2012.

Holt M et al. HIV-negative and HIV-positive gay men’s attitudes towards antiretroviral-based prevention: similar attitudes to pre-exposure prophylaxis (PrEP) but greater skepticism among HIV-negative men about “treatment as prevention.” Nineteenth International AIDS Conference, Washington DC, abstract TUAC0301, 2012.

Krakower D et al. Anticipated risk compensation with pre-exposure prophylaxis use among North American men who have sex with men using an internet social network. Nineteenth International AIDS Conference, Washington DC, abstract TUAC0302, 2012.

Yang D et al. Acceptability of HIV pre-exposure prophylaxis (PrEP) with Truvada among men who have sex with men (MSM) and male-to-female transgender persons (TG) in northern Thailand. Nineteenth International AIDS Conference, Washington DC, abstract TUAC0303, 2012.

View complete listings of the session presentations, with links to abstracts and webcasts, on the conference website here and here.