In an effort to alleviate the inconvenience and other drawbacks of life-long daily treatment, many patients with HIV wish to take "drug holidays," or periodic breaks from antiretroviral therapy.

Several studies -- including the large SMART treatment interruption trial -- have shown that CD4-guided treatment interruption is a potentially hazardous strategy, leading to an increased risk of both opportunistic infections and serious non-AIDS-defining disease.

But a different type of treatment interruption -- a short-cycle strategy alternating periods of 5 days on and 2 days off drugs -- may be feasible for some people, according to a study presented at the 9th International Congress on Drug Therapy in HIV Infection (HIV9) last week in Glasgow, Scotland.

The FOTO study ("Five On, Two Off") included 60 U.S. patients taking tenofovir, emtricitabine, and efavirenz -- the 3 drugs in the Atripla fixed-dose combination pill -- who had a CD4 count above 200 cells/mm3 (mean about 670 cells/mm3) and sustained viral suppression. Most (83%) were men, three-quarters were white, and the mean age was about 45 years.

Participants were randomly assigned to either continue daily therapy or switch to alternating 5 consecutive days on treatment (typically Monday-Friday) followed by 2 days off. HIV RNA levels were assessed at weeks 4, 12, and 24; in the FOTO arm, viral load was measured at the end of a 2-day interruption.

The primary endpoint was the proportion in each arm with virological suppression < 50 copies/mL at week 24. Data on adverse events (AEs), adherence, and quality of life were also collected.

Results

• 53 participants completed 24 weeks in the study (25 in the FOTO arm and 28 in the daily treatment arm).

• All 7 patients who stopped the study prior to week 24 had HIV RNA < 50 copies/mL at the time of discontinuation.

• 10 viral load "blips" (transient increases to 50-500 copies/mL) were detected in the FOTO arm compared with 8 in the daily therapy arm.

• No participants in either arm experienced virological failure (confirmed HIV RNA > 400 copies/mL) through week 24.

• In an intent-to-treat (drop out = failure) analysis, 83% of participants in the FOTO arm and 80% in the daily therapy arm had HIV RNA < 50 copies/mL at week 24 (not a statistically significant difference).

• In an as-treated analysis, 100% in the FOTO arm and 85% in the daily treatment had undetectable viral load at week 24.

• Week 24 viral suppression rates were deemed equivalent in the 2 arms, with the study powered to detect a 15% difference

• CD4 cell counts remained high, and were similar in both arms.

• No AIDS-related events occurred in either arm.

• 3 mild neuropsychiatric AEs were reported, 2 in the FOTO arm and 1 in the daily therapy arm.

"These data confirm the success of a Five-day On/Two-day Off strategy for maintaining virologic suppression for at least 24 weeks on [efavirenz/tenofovir/emtricitabine]," the investigators continued.

In addition to improved convenience for patients in wealthy countries, they noted, "This treatment strategy could significantly reduce antiretroviral drug costs, which is especially important in resource-scarce areas."

Continued follow-up is ongoing to further assess the durability of this strategy over a longer term.

Community Research Initiative of New England, Boston, MA; AIDS Research and Treatment Center of the Treasure Coast, Fort Pierce, FL; Orlando Immunology Center, Orlando, FL; Kinder Medical Group, Miami, FL; Whitman-Walker Clinic, Washington, DC; Community Research Initiative of New England, Springfield, MA; Baystate Medical Center, Springfield, MA.

11/18/08

Reference
C Cohen, A Colson, G Pierone, and others. O214 The FOTO study: 24-week results support the safety of a 2-day break on efavirenz-based antiretroviral therapy. 9th International Congress on Drug Therapy in HIV Infection. Glasgow, Scotland. November 9-13, 2008. Journal of the International AIDS Society 11(Suppl 1):O19. November 10, 2008.