Lopinavir/Ritonavir in PLWH With High-Grade AIN

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

* To evaluate the safety and tolerability of intra-anal administration of lopinavir/ritonavir, administered via suppository with 3 different schedules, in PLWH with high-grade anal intraepithelial neoplasia (HGAIN) (AIN 2/3).

Secondary Objectives

* To measure the effect of intra-anal topical lopinavir/ritonavir administration * To evaluate clearance of human papillomavirus (HPV) * To elucidate the mechanism of action of protease inhibitors

• Number of Participants in the Expansion Cohort Who Experience Regression of AIN2/3 Determined by Pathology [Срок оценки: week 12, week 40]
• Number of Participants in the Expansion Cohort Determined clear of HPV by PCR test [Срок оценки: week 12, week 40]
• Number of Tissue Samples with evidence of apoptosis measured by presence of Activated Caspase 3 [Срок оценки: week 12, week 40]
• Number of Tissue Samples with evidence of autophagy measured by presence of LC3β and p62 [Срок оценки: week 12, week 40]
• Number of Tissue Samples with evidence of cellular proliferation measured by presence of Ki-67 [Срок оценки: week 12, week 40]
• Number of Tissue Samples with evidence of HPV positivity measured by presence of p16 [Срок оценки: week 12, week 40]
• Number of Tissue Samples with p53 expression [Срок оценки: week 12, week 40]