Lopinavir/Ritonavir in PLWH With High-Grade AIN

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 * 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

Inclusion Criteria: * willing to provide informed consent * greater than or equal to 18 years of age * Diagnosis of biopsy-confirmed HGAIN * willing to comply with all study procedures Exclusion Criteria: * Diagnosis of low-grade anal dysplasia (AIN, low-grade squamous intraepithelial lesion (LSIL)) by HRA. * CD4 count less than 200 cells/mm\^3 at the time of consideration for entry into the study * unable to provide informed consent * Pregnant or breastfeeding female * Currently receiving systemic chemotherapy or radiation therapy for another cancer.