Pre-exposure prophylaxis (PrEP) was a focus this morning at CROI.
After the iPrex study and it's open label extension iPrex OLE established good efficacy of PrEP among individuals who adhered to the drug, there has been considerable focus on establishing the conditions for effective (real world) use of PrEP among people at high risk of HIV. In short PrEP needs to be targeted to people engaged in high risk practices and there need to be high levels of adherence to the drug. As we know, adherence is not necessarily simple or easy for everyone.
Two studies of PrEP effectiveness among gay men reported this morning. Both studies received considerable attention last year when they closed their control arms earlier than expected and moved to offer all their participants immediate PrEP, suggesting that this prevention approach is proving to be very effective. At the time, though, there was limited detail about how, why and the extent to which risk was reduced.
The PROUD study is based in England among gay men who were either provided Truvada immediately or after a delay. Dosing was dailly. They both reported an 86% relative reduction in risk of HIV infection among those on PrEP.
The IPERGAY study is based in France and Quebec and used intermittent "on demand" dosing with pills taken before and after sexual intercourse--two before and two after. Whether or not participants actually dosed intermittently (or took the equivalent of a daily dose) was answered with an average of 16 pills per month used. On occasions where PrEP was not used other risk reduction strategies were employed, showing that this approach can be mixed and matched by gay men as appropriate.
Importantly neither study found evidence of risk compensation. Partipants' behaviors were classified as high risk on enrollment and this did not change while on PrEP. This underlines the importance of properly targeting the technology.
The other real world consideration discussed this morning was implementation, including cost. PrEP is currently only approved in the US and while many health insurers notionally cover it, many people are encountering high co payments for particular scripts or expensive plans to start with. Some community groups are training up 'navigators' to help potential PrEP users sort out the complex bureaucracy of insurance eligibility.
Meanwhile in countries with public insurance schemes like Australia, the drug manufacturer has been slow in seeking a license. Hopefully this will change in the coming year. Meanwhile ASHM and partners have published guidance for clinicians and individuals wishing to use PrEP including options for importation of generic drug. At around $3 per pill such drug is affordable to many Australians. Equity questions remain to be addressed for those who cannot afford it or who lack the wherewithal to obtain the drug in this way.
Meanwhile the news for PrEP among women in the form of Tenofovir gel was not good with the South African FACTS 001 study finding no HIV risk reduction among those using the drug versus those using placebo. In a thoughtful analysis Helen Rees concluded that socio-cultural issues play a large part in determining adherence and therefore effectiveness. Young South African women face a variety of structural inequity issues that limit their ability to reduce the risk of HIV. The study included a social science arm with qualitative interviews and it will be fascinating to see those findings in the future.
Finally, a study of PrEP as a bridge to ARV as prevention reported excellent results. The PARTNER demonstration study was based in sub-Sahran Africa among heterosexual serodiscordent couples. It aimed to get the HIV positive partner onto treatment and undetectable and in the meantime (6 months from treatment initiation) provided PrEP to the HIV negative partner. It showed a 96% reduction in the risk of HIV infection. This seems like a logical and cost effective way to dovetail the two technologies for prevention.
All this means that PrEP is likely to continue to be a hot topic in HIV prevention for some time yet.