A Phase 1 interventional study of Lopinavir / Ritonavir in High-Grade Anal Intraepithelial Neoplasia, sponsored by University of Wisconsin, Madison. Recruiting at 1 site in United States. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-05-15.
Sponsored by University of Wisconsin, Madison · Phase 1, Interventional, and Prevention
This study is being done to assess the safety of lopinavir/ritonavir in patients with PLWH with AIN. 30 participants will be recruited and can expect to be on active study for approximately 3 months and long term follow up for 40 weeks.
This is a Phase I modified 3 + 3 design, in which the maximum tolerated dose (MTD) will be identified. The 3 + 3 dose escalation will consist of 6 dose levels (18 participants; planned escalation described in arms below) in combination with variation in dosing schedules of the drug lopinavir/ritonavir. This design also allows for some possible intermediate doses to be examined if dose-limiting toxicities (DLTs) occur and de-escalation is needed.
An expansion cohort of 12 participants will occur at the MTD. Once the MTD is determined, then secondary outcomes will be evaluated.
Primary Objective
Secondary Objectives
University of Wisconsin, Madison is the lead sponsor of 1,161 studies on the registry; 182 are open to participants now.
Of its 151 completed or terminated interventional studies of FDA-regulated products, 114 (75%) have results posted.
Counted across the registry records on this site, refreshed daily.
Exclusion Criteria:
Cohort 1 will receive two 5-day cycles of the low dose of the suppository (Lopinavir/Ritonavir (200mg/50mg)) in Weeks 0 and 2
Drug: Lopinavir / Ritonavir
Cohort 1b will receive three 5-day cycles of the low dose of the suppository (Lopinavir/Ritonavir (200mg/50mg)) in Weeks 0, 2, and 4 if Cohort 2 has one dose-limiting toxicity (DLT).
Drug: Lopinavir / Ritonavir
Cohort 2 will receive two 5-day cycles of the higher dose of the suppository (Lopinavir/Ritonavir (400mg/100mg)) in Weeks 0 and 2, if Cohort 1 dose is safe.
Drug: Lopinavir / Ritonavir
Cohort 2b will receive three 5-day cycle of the higher dose of the suppository (Lopinavir/Ritonavir (400mg/100mg)) in Weeks 0, 2 and 4 if Cohort 3 has one DLT.
Drug: Lopinavir / Ritonavir
Cohort 3 will receive two 5-day cycles of the highest dose of the suppository (Lopinavir/Ritonavir (600mg/150mg)) in Weeks 0 and 2, if the Cohort 2 dose is safe.
Drug: Lopinavir / Ritonavir
Cohort 4 will receive three 5-day cycles of the highest dose of the suppository (Lopinavir/Ritonavir (600mg/150mg)) in Weeks 0, 2, and 4, if the Cohort 3 dose is safe.
Drug: Lopinavir / Ritonavir
Human Immunodeficiency Virus (HIV) antiviral, given via suppository
Maximum Tolerated Dose (MTD) as determined by the number of participants at each dose level in the escalation cohorts who experienced a dose-limiting toxicity (DLT)
The MTD is the highest explored dose of lopinavir/ritonavir is the dose at which less than 33% of patients experienced a DLT. A DLT is defined as any toxicity at least possibly related to ritonavir/lopinavir with a drug-related Grade greater than or equal to 3.
Time frame: up to 5 weeks
Rate of Grade 3 or above Toxicities in any Organ System in the Escalation Cohorts
Grade 3 or above as delineated in Common Terminology Criteria for Adverse Events v 5.0 (CTCAE)
Time frame: up to 5 weeks
Number of Participants in the Expansion Cohort Who Experience Regression of AIN2/3 Determined by Pathology
Efficacy of intra-anal topical lopinavir/ritonavir administration determined by pathology, based on the regression of AIN2/3 at study weeks 16, 28, and 40. Regression defined as either AIN1 or no AIN lesion detected by High resolution anoscopy (HRA)/biopsy and anal cytology. Down grade of disease from AIN2/3 to AIN1 or normal.
Time frame: week 12, week 40
Number of Participants in the Expansion Cohort Determined clear of HPV by PCR test
HPV clearance determined by quantitative polymerase chain reaction (PCR) test.
Time frame: week 12, week 40
Number of Tissue Samples with evidence of apoptosis measured by presence of Activated Caspase 3
Mechanism of action of protease inhibitors investigated with biomarker studies (immunohistochemistry and Immunofluorescence of tissue). Samples with activated caspase 3 indicate evidence of apoptosis.
Time frame: week 12, week 40
Number of Tissue Samples with evidence of autophagy measured by presence of LC3β and p62
Mechanism of action of protease inhibitors investigated with biomarker studies (immunohistochemistry and Immunofluorescence of tissue). Samples with LC3β and p62 indicate evidence of autophagy.
Time frame: week 12, week 40
Number of Tissue Samples with evidence of cellular proliferation measured by presence of Ki-67
Mechanism of action of protease inhibitors investigated with biomarker studies (immunohistochemistry and Immunofluorescence of tissue). Samples with Ki-67 indicate evidence of cellular proliferation.
Time frame: week 12, week 40
Number of Tissue Samples with evidence of HPV positivity measured by presence of p16
Mechanism of action of protease inhibitors investigated with biomarker studies (immunohistochemistry and Immunofluorescence of tissue). Samples with p16 indicate evidence of HPV positivity.
Time frame: week 12, week 40
Number of Tissue Samples with p53 expression
Mechanism of action of protease inhibitors investigated with biomarker studies (immunohistochemistry and Immunofluorescence of tissue).
Time frame: week 12, week 40
Plan to share: No
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University of Wisconsin, Madison