The present study evaluated the efficacy of intermittent antiviral treatment administered to HIV-infected patients under stepwise reductions in weekly medication. Forty-eight patients were invited to reduce their antiviral medication to 5 consecutive days per week; after control over HIV activity was ascertained, antiviral drugs were cut to 4 consecutive days per week. Of the 48, 39 then reduced medicines further to 3 d, and 12 of those eventually undertook a 2 d/wk schedule. Clinical and immunological status and plasma HIV load were repeatedly monitored. HIV was unremittingly maintained below detection levels in all patients under either 5- or 4-d/wk treatment regimens, for a mean 56 ± 40 wk/patient (5-d regimen) and 84 ± 46 wk/patient (4-d regimen). Of the 39 patients under 3-d regimens, 35 maintained optimal control over HIV activity for a mean 50 ± 32 wk, as did 10 of the 12 under 2-d regimens, for 24 ± 10.5 wk. Summing up treatment 5 d/wk, plasma HIV remained below detection levels for a cumulative 8895 wk (170 patient-yr). No major HIV-related clinical event was reported. and CD4⁺ T-cell counts and percentages readily increased over the last value noted under the 7-d treatment course. Viral failure was documented in 6 of the 48 patients: 4 under a 3-d/wk regimen, 2 under a 2-d/wk regimen. All 6 patients had their treatment swiftly set back to a 7-d/wk regimen, resulting in rapid control over HIV replication. In summary, intermittent antiretroviral regimens optimally suppressed HIV in patients taking antiviral medicines 5 and 4 d/wk, as well as in a substantial proportion of patients under 3- or 2-d/wk antiviral regimens, reducing both expenses and, possibly, drug toxicity. Controlled prospective clinical trials are warranted before considering short weekly cycles of antiretroviral medicines an alternative in the management of chronically HIV-infected patients.—Leibowitch, J., Mathez, D., de Truchis, P., Perronne, C., Melchior, J. C. Short cycles of antiretroviral drugs provide intermittent yet effective therapy: a pilot study in 48 patients with chronic HIV infection.