Figure 1

A. A schematic drawing SIV_mne inoculations and treatment regimens of different groups. Arrows show schedule of SIV_mne inoculation. The solid horizontal bar indicate schedule of daily PMPA treatment (30 mg/kg, subcutaneous). AID₅₀ is 50% animal infectious dose of the SIV_mne used in the studies. One AID₅₀ of the SIVmne stock was approximately10 50% tissue culture infectious dose (TCID₅₀) by intravenous inoculation, and 100 TCID₅₀ by intrarectal inoculation. Macaques in groups B (plus macaque 93043 in group D) received a 10-week PMPA treatment beginning 24 hours after virus inoculation, including treatment interruption plus SIV_mne re-inoculation with 10 AID₅₀ SIV_mne at weekly intervals during the first six weeks of treatment. Macaques in groups C and D received a 5-week PMPA treatment starting 24 hours after virus inoculation, including one treatment interruption plus SIV_mne re-inoculation with 10 AID₅₀ SIV_mne at week 1 of treatment. Macaque 95020 (group E) was untreated. B. The exact timing of events during the 72 hour interruption, including timing of SIV_mne re-inoculation during the treatment interruption. Treatment was initiated 24 hours after SIVmne inoculation, then continued for 5 days. Thereafter, treatment was withheld for 72 hours, during which macaques were re-inoculated with SIV_mne at 48 h and re-started on treatment at 72 h. After the last inoculation, treatment was continued uninterrupted for 28 days. Note that the during the treatment interruption, the 48-hour interval between the end of treatment and SIV_mne re-inoculation was approximately one half-life of PMPA active metabolites in resting lymphocytes or three times the half-life in activated lymphocytes [26].