Intervention and mode of delivery (Figs 
toxicity, toxicities, HRA/biopsy
ANAL DYSPLASIA, ADVERSE EVENT, LOW-GRADE SQUAMOUS INTRAEPITHELIAL LESION, ADVERSE EVENTS, HSIL, ADVERSE EVENT, REGRESSION
Participants with anal HSIL biopsies in the previous 8 weeks were screened for study participation. At the time of signing consent, the presence of residual HSIL was documented by HRA. The time between screening for study eligibility and week 0 (study commencement) was ≤ 4–6 weeks.Artesunate suppositories (Frantz Viral Therapeutics, LLC) were administered intra-anally through a 3+3 dose escalation schema (doses: 200 mg, 400 mg, 600 mg) in which the maximal tolerated dose was identified, with the safeguard of an integrated de-escalation schema. The lowest dose level was two 5-day cycles of artesunate, followed by three five-day cycles of artesunate. In the absence of toxicity, patients were enrolled at the next highest dose in the same manner.During the week 0 clinic visit, the first suppository of the entire treatment regimen was inserted digitally into the anal canal by the healthcare provider, while the patient was in the left lateral position. Patients were instructed to insert the remaining suppositories at bedtime using the same technique shown by the clinician.The study team performed a follow-up phone call the week after each treatment cycle began to document compliance with the study medication and any adverse events. At weeks 2, 4, 6, the anoscopic exam assessed for the presence of local mucosal reactions, and symptom diary cards were reviewed, graded, and causality to the study drug assessed by the clinician. Initial screening and follow-up (weeks 16, 28, 40) studies included anal cytology, HPV genotyping (AmpFire HPV genotyping assay, Atila Biosystems, Inc, Sunnyvale, CA), and HRA. HRA-directed biopsies were obtained at week 16, and if clinically indicated, at weeks 28 and 40.The primary outcome/endpoint was to evaluate the safety and tolerability of intra-anal artesunate. Safety reporting consisted of all adverse events (AEs) reported by patients during the dosing phase of the study and for one month following the last dose of Artesunate. Relatedness of an AE to study treatment was assessed by the investigator.A dose-limiting toxicity was defined as any drug-related Grade 2 or greater, drug-related toxicities in any organ system as delineated in Common Terminology Criteria for Adverse Events v4.0. Tolerability was defined as the percentage of participants who completed the dosing regimen without any drug-related serious adverse event (SAE).Secondary outcomes/endpoints for efficacy included the following:Complete histologic regression is defined as either regression to LSIL (low-grade squamous intraepithelial lesion) or no anal dysplasia detected by HRA/biopsy and anal cytology at week 16 and over the study window. Partial regression is defined as: (1) clearance of intra-anal HSIL, but not perianal HSIL in a patient who had both or (2) >50% reduction of the area of HSIL lesions compared to the area of anal HSIL seen on screening HRAClearance of detectable HPV genotypes identified at the screening evaluation that became undetectable consistently through serial HPV genotyping over the study window. New genotypes acquired during the study were not included in evaluation.Descriptive summary statistics were used to assess demographic characteristics, safety, and regression of anal HSIL. Categorical data were summarized using frequencies and relative frequencies (i.e., proportions). Continuous data were summarized by mean or median with the range.