A trial of SGN-00101 (HspE7) to treat high-grade anal intraepithelial neoplasia in HIV-positive individuals

Objectives: To test a therapeutic vaccine consisting of a fusion of the human papillomavirus (HPV) 16 E7 protein and the Mycobacterium bovis heat shock protein 65 (SGN-00101) to treat high-grade anal intraepithelial neoplasia (HG-AIN) in HIV-positive individuals. Design: A phase I/II trial with three cohorts of five participants each, sequentially assigned to receive 100, 500 or 1000 mu g SGN-00101, injected three times subcutaneously in alternating thighs at 4-week intervals. Anal disease was assessed at baseline, 8, 12, 24 and 48 weeks and was classified as the more severe of anal cytology and anal biopsy. Anal HPV DNA was detected using L1 consensus primer-based PCR followed by type-specific probing and dot-blot hybridization (DBH). HPV16, 18 and 31 DNA copy numbers were measured using quantitative real-time PCR. Setting: University-based research clinic. Participants: Thirteen HIV-positive men and two HIV-positive women with HG-AIN. Results: There were no drug-related serious adverse events or significant changes in HIV viral load and CD4/CD8 ratio. At 48 weeks, two of five participants in both the 100 and 500 mu g cohorts regressed to AIN 1 and one of five participants in the 1000 mu g cohort regressed to atypical squamous cells of undetermined significance (ASC-US). All participants had at least one oncogenic HPV type at baseline. Three of five (60%) participants who regressed to AIN 1 or ASC-US became HPV-negative using DBH and real-time PCR, compared with none of 10 participants with no clinical response (P = 0.02). Conclusions: SGN-00101 was well tolerated in HIV-positive individuals, with preliminary evidence for clinical activity.