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Evidence that “on-demand” PrEP taken before and after sex can prevent HIV

, by Emily Land

PrEP pillHow many doses of Truvada-based PrEP (pre-exposure prophylaxis) are needed to provide adequate protection against HIV? Might it be possible to take PrEP only before and after sex—instead of every day?

In the U.S., once-daily dosing with Truvada is the only approved method of PrEP by the FDA—since continuous therapy provides the most complete protection against HIV. Researchers are now investigating, however, if other dosing schedules may also be effective—to reduce cost and also provide the most flexibility to PrEP users.

A recent article published in The Lancet HIV provides insight into this very question. The researchers report the results from a very small pharmacokinetic study with 21 HIV-negative participants. The participants, who took Truvada daily for a total of 30 days, had the level of drug measured in their blood at day 1 (after their first dose), 3, 7, 20, and 30. Based on drug concentration modelling, the researchers were able to estimate the proportion of people who achieved protective levels of drug with each different dose level.

Here’s what they found:

  • 84% of people achieved an estimated 98% reduction in HIV risk with four doses; and,
  • 90% of people achieved an estimated 99% reduction in HIV risk with seven doses.

(For one isolated sexual encounter, the minimum number of Truvada doses a person would take under currently investigated “on-demand” dosing regimens is four.)

Researchers have previously investigated, with a study named IPERGAY, whether “on-demand” PrEP dosing might be effective. In this study, which reported an estimated 97% HIV risk reduction, participants took two tablets of Truvada two to 24 hours before sex, then one tablet 24 after sex, and a final tablet 48 hours after sex. However, people included in this study were having sex on a regular basis—meaning that they ended up taking Truvada fairly frequently.

After the results of IPERGAY were released, the question then became—how much protection do people get from on-demand dosing if they aren’t having sex as frequently?

“Drug concentration modelling on the basis of pharmacological studies suggests that the event-driven four-tablet regimen (two-tablet loading dose, two doses after exposure) can confer high protection for MSM [men who have sex with men] and transgender women even for infrequent sexual exposures,” the authors conclude.

The current findings are applicable to people who may be exposed to HIV through anal—but not vaginal—sex. “Therapeutic drug concentration may decline more rapidly in vaginal tissue than in rectal tissue, indicating that controlled studies are needed for event driven dosing strategies in women,” the authors note.

Daily dosing of Truvada for PrEP is currently the only PrEP regimen approved by the U.S. FDA to reduce the risk for HIV infection. Keep up-to-date with new PrEP development and dosing strategies by reading BETA and subscribing to our weekly e-mail.


Glidden, D. V., Anderson, P. L. and Grant, R. M. Pharmacology supports on-demand PrEP. The Lancet HIV. September, 2016.


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