FOTO (Five Days On, Two Days Off) Study

In 2005, a pilot study initiated and conducted by Community Research Initiative investigators suggested a novel short-cycle intermittent treatment approach for HIV might be an effective way to sharply cut the cost of treating the disease and enhance the quality of life of patients facing decades of powerful and sometimes toxic drugs and periodically accompanied by devastating side effects.

Researchers theorized that medication levels might not be significantly affected by a two-day break from drugs, assuring that the virus would remain in check. Tests showed after 48 weeks in the pilot FOTO (Five Days On, Two Days Off) study, for all patients on efavirenz-based antiretroviral therapy, the virus stayed suppressed and their immune systems intact.

An effective short-cycle intermittent treatment approach would address a number of problems associated with continuous therapy for HIV infection, including:

  • Adherence concerns. “Pill fatigue” associated with daily treatment often leads to erratic adherence and treatment failure.
  • Drug toxicity. Cumulative exposure to highly potent antiretroviral therapy may involve toxicities and side effects for many patients.
  • The high cost of therapy. The 5/2 intervention would reduce the cost of HIV medications by 29% for individuals on efavirenz-based antiretroviral therapy. This represents an approximate annual cost savings per patient of $4,060.

To follow up on the positive results of the pilot study, 60 subjects, all on daily efavirenz/tenofovir/emtricitabine (EFV/TDF/FTC) with CD4 count>200 and durable viral suppression, were randomized to continue daily therapy or change their weekly schedule to five consecutive days on treatment (typically Monday–Friday) followed by two days off treatment (five on, two off, or “FOTO” schedule). The primary endpoint was the proportion in each arm with virologic suppression (VL<50) at week 48.

These data confirmed the success of a FOTO strategy for maintaining virologic suppression for at least 48 weeks on EFV/TDF/FTC. This treatment strategy could significantly reduce antiretroviral drug costs, which is especially important in resource scarce areas.