Prospective PrEP users sometimes ask:
How many tablets of PrEP (using FTC/TDF also known as Truvada) are required for protection?
After the last possible exposure to HIV, how many post exposure tablets need to be taken?
In my opinion, the appropriate answer depends on whether the possible exposure to HIV is by anal intercourse or by vaginal intercourse.
There is some evidence that among MSM and trans women concerned about HIV transmission by receptive anal sex:
- 2 tablets before anal sex provides some protection (maybe 84%), provided they continue after sex,
- 4 tablets before anal sex provides nearly full protection for some people, provided they continue after sex,
- 7 tablets before anal sex provides nearly full protection for nearly all people, provided they continue after sex,
- Do not take more than 2 tablets in a day, or more than 7 tablets in a week.
On-demand dosing makes what to say about starting and stopping easy. On-Demand dosing is known to be effective for MSM (See the references on the Ipergay study); cis and trans women were not included in that study. On demand dosing involves 2 tablets taken before sex (2 to 24 hours), a third tablet taken the day after sex, and forth tablet taken 2 days after sex. There is only one effectiveness study for on demand dosing (Ipergay) while the effectiveness of daily dosing for MSM/TGW has been evaluated in 2 trials (iPrEx and Proud). So far, only daily usage of PrEP is recommended in the US by the FDA and the CDC. The European AIDS Clinical Society also suggests that on-demand dosing is an alternative for men who have sex with men, whose risk of acquiring HIV mainly arises from "bottoming" or receptive anal intercourse. This is the main way of exposure to HIV for trans women as well.
For women and cisgender men concerned about HIV transmission by vaginal sex, more tablets are needed because the concentrations of the active form of tenofovir (TFV-DP) in the vagina reach lower levels compared with the rectum (by as much as 20 fold). Furthermore, detailed analysis linking different concentrations of PrEP medications with different levels of protection have not be completed or presented. The pharmacological modeling and some evidence suggests that:
- 3 tablets before vaginal sex provides some protection, provided they continue after sex,
- 7 tablets before vaginal sex provides nearly full protection, provided they continue after sex.
How long after the last possible exposure to HIV should people continue to take PrEP? A cautious and simple answer would be 28 days, as this is the equivalent of post-exposure prophylaxis, and does not depend on how many pre-exposure doses were taken. This amount of time also allows people to think about whether the "last possible exposure to HIV" will really be the last - it may take a while to learn what the course of one's sexual practices will be. The Ipergay trial suggests that 2 days after the sexual exposure might be enough, provided that the pre-sex doses were taken on time. Whether this is sufficient to provide FULL protection for ALL MSM is not yet known. Women were not included in that study. The modeling done by Cottrell et al suggests after daily dosing, the medication concentrations remains high in the rectum for about 7 days after the last dose. So there is no clarity on how long to continue PrEP after sex. One approach might be:
- 28 days is definitely long enough (for men or women) regardless of how much pre-exposure dosing was taken,
- 2 days may be long enough for MSM if pre-exposure doses were taken on time (there is no information regarding less than 28 days dosing after vaginal sex).
Again, definitive answers are not available, so this story may change going forward.
References and Notes:
Anderson, P. L., D. V. Glidden, A. Liu, S. Buchbinder, J. R. Lama, J. V. Guanira, V. McMahan, L. R. Bushman, M. Casapia, O. Montoya-Herrera, V. G. Veloso, K. H. Mayer, S. Chariyalertsak, M. Schechter, L. G. Bekker, E. G. Kallas and R. M. Grant (2012). "Emtricitabine-Tenofovir Concentrations and Pre-Exposure Prophylaxis Efficacy in Men Who Have Sex with Men." Sci Transl Med 4(151): 151ra125.
Notes: Correlates blood cell concentrations of the active form of tenofovir (TFV-DP) with HIV incidence reduction in iPrEx randomized clinical trial and numbers of tablets taken per week. Concentrations commensurate with use of 7 tablets per week were associated with a 99% reduction in HIV incidence. In fact, there were no infections that occurred at that concentration.
Grant, R. M., P. L. Anderson, V. McMahan, A. Liu, K. R. Amico, M. Mehrotra, S. Hosek, C. Mosquera, M. Casapia, O. Montoya, S. Buchbinder, V. G. Veloso, K. Mayer, S. Chariyalertsak, L. G. Bekker, E. G. Kallas, M. Schechter, J. Guanira, L. Bushman, D. N. Burns, J. F. Rooney, D. V. Glidden and t. iPrEx study (2014). "Uptake of pre-exposure prophylaxis, sexual practices, and HIV incidence in men and transgender women who have sex with men: a cohort study." Lancet Infect Dis 14(9): 820-829.
Notes: The iPrEx open label extension shows no new infections among MSM and TGW who had drug levels commensurate with use of 4 or more tablets per week. There was only two infections among people with drug concentrations indicating use of 2 to 3 tablets per week, still an 84% reduction in HIV incidence.
Donnell, D., J. M. Baeten, N. N. Bumpus, J. Brantley, D. R. Bangsberg, J. E. Haberer, A. Mujugira, N. Mugo, P. Ndase and C. Hendrix (2014). "HIV protective efficacy and correlates of tenofovir blood concentrations in a clinical trial of PrEP for HIV prevention." Journal of acquired immune deficiency syndromes (1999) 66(3): 340.
Notes: There was a 90% reduction in HIV risk among heterosexual men and women who had PrEP medications detected in the blood plasma. Detection of drug in the blood plasma suggests that medication was taken in the past 3 days; the numbers of tablets taken per week cannot be estimated.
Cottrell, M., K. Yang, H. Prince, C. Sykes, N. White, S. Malone, E. Dellon, R. Madanick, N. Shaheen, M. Hudgens, J. Wulff, K. Patterson, J. Nelson and A. Kashuba (2016). "A Translational Pharmacology Approach to Predicting HIV Pre-Exposure Prophylaxis Outcomes in Men and Women Using Tenofovir Disoproxil Fumarate ± Emtricitabine." J. Infect. Dis.
Notes: A pharmacological modeling study is consistent with observations from trials suggesting that use of 4 tablets per week would be fully protective for anal intercourse, while full vaginal protection may require 6 to 7 tablets per week.