Title: Extended-release Pre-Exposure Prophylaxis and Drug Resistant HIV
Speaker : Yanping Ma, Associate Professor, Loyola Marymount University;
When: April 07, 2-3pm;
Where: Phillips 736;
Collaborations with Yeona Kang and Angelica Davenport and Jennifer Aduamah and Kathryn Link and Katharine Gurski
Abstract: The pharmacologic tail of long acting cabotegravir (CAB-LA, injectable PrEP) allows months-long intervals between injections, but it might encourage the growth of drug-resistant HIV strains during the acute infection stage. We present a within-host, mechanistic Ordinary Differential Equation model of the HIV latency and infection cycle in CD4+ T-cells to investigate. We develop a pharmacokinetic/pharmacodynamic model for long acting cabotegravir (CAB-LA, injectable PrEP) to relate the inhibitory drug response to the drug concentration in plasma as well as rectal, cervical, and vaginal fluids and tissue. After validating our model against experimental results, we build in-silico trials. First, we separately administer CAB-LA to the in-silico macaque and human patients prior to and post-SHIV/HIV exposure, to observe SHIV and HIV infectivity dynamics, respectively. The model does not include a mechanism for CAB-LA to generate drug-resistant HIV mutations, but we observe the result when mutations arise naturally. We find CAB-LA may encourage the drug-resistant strain to grow and to outcompete the wild-type in the acute stage. The in-silico trials show that the level of drug resistance, the effectiveness of CAB-LA against the mutations, and the degree of fitness for the mutant strain of virions to infect T-cells determine the course of the drug-resistant strain.