The American public health agency, the Centers for Disease Prevention and Control (CDC), today released guidelines for the use of Truvada by HIV-negative gay and bisexual men wishing to reduce their risk of HIV infection. While the CDC highlights a number of uncertainties and concerns about pre-exposure prophylaxis (PrEP), they have issued their ‘interim guidance’ just two months after the first positive results of a research trial into the approach.
They have done this, they say, because: “Concerns exist that without early guidance, various unsafe and potentially less effective PrEP-related practices could develop among health-care providers and MSM beginning to use PrEP in the coming weeks and months.”
Prescriptions should only be given for 90 days at a time, with HIV testing, adherence counselling, sexually transmitted infection check-ups, sexual risk counselling and condoms provided before new prescriptions are issued.
The guidelines state that PrEP should only be provided for men who have sex with men, specifically those who are “at substantial, ongoing, high risk for acquiring HIV infection”.
Pre-exposure prophylaxis involves HIV-negative people taking antiretroviral medications in order to reduce their risk of acquiring HIV. In November, a study conducted with gay and bisexual men in six countries showed that daily use of the two drugs tenofovir and FTC (combined in one pill as Truvada) reduced the risk of infection by 44%. However many of the gay and bisexual men participating in the trial did not take the pills each day, as prescribed. In men who did take the drugs consistently, results seemed to be much better. In men with very poor adherence, results were worse.
However extensive analysis of the adherence data from the trial has not yet been completed, nor have the trial results been replicated in other settings.
The CDC only endorses a model of Truvada prescribing that is very close to that carried out in the trial setting. That is why its use is limited to high-risk gay and bisexual men.
The guidance gives quite a broad indication of which men PrEP may be suitable for, citing only lack of condom use in combination with “frequent partner change or concurrent partners in a geographic setting with high HIV prevalence” as examples.
The CDC says that antiretrovirals other than Truvada should not be used for PrEP and that the same daily dosing schedule that was employed in the trial must be followed. Therefore, ‘intermittent’ dosing (i.e., before or after sex) is not endorsed.
Moreover adherence support must be a “routine component of any PrEP program”. It should be provided before PrEP is issued, and then at least every 90 days.
Similarly, PrEP should only be delivered “as part of a comprehensive set of prevention services” that includes risk-reduction counselling, ready access to condoms and the diagnosis and treatment of sexually transmitted infections. These activities should take place each 90 days, before a new prescription is issued.
Before PrEP is provided, clinicians must also check that the patient is HIV-negative. If he has any signs or symptoms that may be linked to HIV seroconversion, RNA testing is recommended. He must also be screened for sexually transmitted infections and hepatitis B, and have his kidney function assessed (Truvada can sometimes harm the kidneys).
Other tests for side-effects are required after three months and then annually. Any serious adverse events should be reported to the Food & Drug Administration (FDA).
Cost remains a central concern. As Truvada is only approved by the FDA for the treatment of HIV and not its prevention, insurance companies are unlikely to pay for PrEP. Doctors are allowed to prescribe it if men have the means to pay for it themselves. A month’s supply of the drug costs around $1000, to which must be added the costs of counselling, side-effects monitoring and medical appointments.
The CDC’s document provides ‘interim guidance’. Further guidelines, with more involvement from stakeholders, are in the process of being developed.
Smith DK et al. Interim Guidance: Preexposure Prophylaxis for the Prevention of HIV Infection in Men Who Have Sex with Men. Morbidity and Mortality Weekly Report 60: 65-68, 2010.