Vaginal 5-fluorouracil for high-grade cervical dysplasia in human immunodeficiency virus infection: A randomized trial

Objective: To compare the efficacy and toxicity of topical vaginal 5-fluoro uracil (5-FU) maintenance therapy against the effects of observation after standard treatment for high-grade cervical. dysplasia in human immunodefici ency virus (HIV)-infected women and to evaluate the association between bas eline CD4 count and time to recurrence. Methods: In a phase III unmasked, randomized, multicenter, outpatient clini cal trial, 101 HIV-positive women either received 6 months of biweekly trea tment with vaginal 5-FU cream (2 g) or underwent 6 months of observation af ter standard excisional or ablative cervical treatment for cervical intraep ithelial neoplasia (CIN). Papanicolaou smears and colposcopy were scheduled at regular intervals during the ensuing 18 months, with the primary end po int being the time at which CIN of any grade recurred. Results: Thirty-eight percent of women developed recurrence: 14 (28%) of 50 in the 5-FU therapy group and 24 (47%) of 51 in the observation group. Tre atment with 5-FU was significantly associated with prolonged time to CIN de velopment (P = .04). Observation subjects were more likely to have high-gra de recurrences, with 31% developing CIN 2-3 compared with 8% in the 5-FU tr eatment arm (P = .014), and disease recurred more quickly in observation su bjects as well. Baseline CD4 count was related significantly to time to rec urrence (P = .04), with 46% of subjects with CD4 counts less than 200 cells /mm(3) developing recurrence compared with 33% of subjects with CD4 counts at least 200 cells/mm3. Disease recurred more slowly in subjects who had re ceived antiretroviral therapy than in antiretroviral therapy-naive subjects . There were no instances of grade 3 or 4 toxicity, and compliance with 5-F U treatment was generally good. Conclusion: Adjunctive maintenance intravaginal 5-FU therapy after standard surgery for high-grade lesions safely and effectively reduced recurrence o f cervical intraepithelial neoplasia in HIV-infected women. (Obstet Gynecol 1999;94:954-61. (C) 1999 by The American College of Obstetricians and Gyne cologists.).