What if PrEP studies demonstrate that either tenofovir or Truvada have some protective effect? The implementation of PrEP may well raise some thorny issues.
Although the results from one trial will probably not change international public health policy, gay men in particular might begin to adopt PrEP informally if they hear of positive results from the first trials. At the moment there’s little evidence that tenofovir or Truvada are being used systematically as PrEP by gay men in the UK. But gay newspapers in the US have reported the informal use of tenofovir in several large cities, and one HIV physician (Marcus Conant of San Francisco) has gone on record to say he has prescribed it to some gay male patients.
In fact PrEP is already being provided by some clinicians to partners of HIV-positive people, to assist in risk reduction when the couple is trying to conceive. Moreover, Swiss researchers in 2007 successfully used two doses of PrEP to protect HIV-negative women trying to conceive with HIV-positive men. These women’s partners had undetectable viral loads and they only had unprotected sex on the days when the woman was most likely to conceive.
Initially PrEP is likely to be prescribed through sexual health clinics, accompanied by regular HIV testing. But some advocates want the drugs with the best safety records eventually to be available over the counter. This approach would shift the cost of providing PrEP to the user, making it more affordable to the NHS in the long term.
The short-term cost of PrEP could be enormous at current drug prices, but its cost needs to be considered in the context of the long-term cost of 7000-plus new people with HIV per year in the UK, each of them requiring antiretroviral therapy for 20 to 40 years or so at an annual cost of £10,000 a year for drugs and care.
The greatest impact on new infections would probably come from targeting PrEP to men with histories of serial risk-taking and repeat testing, to HIV-negative gay men with a high number of sexual partners, and to HIV-negative men and women in HIV-discordant relationships, especially women seeking to conceive.
However, the first generation of trials may still leave a range of questions partially unanswered:
- Is daily dosing necessary or can episodic dosing provide equivalent protection? Will other drugs with longer half-lives make episodic dosing a possibility?
- How long does PrEP remain effective in a population? Is there a decline in adherence?
- What effect does taking PrEP have in individuals who acquire HIV infection? Do they develop resistance and do they transmit drug-resistant virus?
- Are there any long-term side effects associated with use of PrEP? People will generally tolerate some side-effects when treating a life-threatening condition, but will be less tolerant of side-effects when guarding against an infection.
- What effect does PrEP have on risk-taking – both among those who take it and in the wider community?
- How does PrEP compare with a topical microbicide containing tenofovir? The VOICE study will test this question in a study that may report in 2011.
- A further strategy may be to combine different types of drugs to prevent infection, such as the use of topical microbicides with oral drug treatment to prevent infection.