non-randomized, non-blinded, multi-center clinical trial using historical
sequentially accrued patients with documented HSV infections (either
skin/eye/mucocutaneous (SEM), CNS, or disseminated) treated with intermediate
dose acyclovir (45 mg/kg/day for 21days) or high dose (60 mg/kg/day
for 21days) to historical controls who received standard dose (30 mg/kg/day
for 10days) therapy.1
- Patients were accrued over an 8 year period (1989-1997) and compared to controls enrolled in a previous trial from 1981-1988.
- The intermediate treatment group had 16 patients, which was too small to adequately assess for meaningful differences between intermediate and high dosing.
- The 72 patients treated with high dose therapy were compared to 107 standard dose controls.
- Overall, patients treated with high dose acyclovir had substantially improved mortality compared to patients who had previously received standard dosing.
- Patients with disseminated HSV had improved mortality (31% compared to 61%, NNT=3) when treated with high dose acyclovir compared with standard dose treatment.
- Elevations in AST, bilirubin, creatinine, and thrombocytopenia were noted in patients with disseminated disease treated with high dose acyclovir but were not compared to controls.
- Neutropenia was found in both patients with disseminated disease and localized CNS disease treated with high dose acyclovir. The neutropenia resolved with moderation of therapy.