Flashcards in Pre-clinical models of HIV prevention Deck (21):
what are the methods of HIV prevention prior to exposure?
behaviour changes; STI treatment; male circumcision; PrEP; vaccines
What are the methods of HIV prevention at the time of exposure?
male and female condoms; lube; cervical barriers; microbicides (vaginal and rectal PrEP)
What is the function of pre-clinical models of HIV?
facilitate and accelerate prioritization of candidate prevention agents ; their combinations, dosing and formulations to be evaluated in large trials
Why is the rectal epithelium particularly vulnerable to HIV infection?
single layer of columnar epithelium which is easily damaged; intestinal lamina propria contains an abundance of highly activated target cells for HIV-1 infection
What are some of the special considerations for the design of preventive strategies at hte mucosal level?
some ARVs may be cytotoxic in the colorectum or may induce immunological toxicity- induce reponse favourable for HIV
What does the cellular model of a co-culture of DCs and PM-1 (Cd4 T cell clone) allow the study of?
mimicks DCs-T cells interaction during viral amplification of the founder population and viral dissemination
What is hte function of the cellular models using epithelial cell lines and primary cells?
assess potential cytotoxicity, disruption of petihleium integrity induced by the candidate microbicide
What is the general function of the cellular models?
very good at screening for microbicides
What are the types of mucosal tissue explants?
cervical, vaginal, penile and colorectal which can be polarised or non-polarised
What can be measured from mucosal tissue explants?
virus in supernatant; proinflammatory cytokines and drug concentration in tissue
What are the limitations of non-human primate models of HIV?
cost; HIV does not replicate efficiently in macaque cells
What other viruses can be used in non-human primate models?
SIV or SHIV- with HIV env or RT
What are hte problems with humanised mice models?
cannot be bred; don't recapitulate basic features of HIV pathogenesis; don't elicit B cell responses upon vaccination
What are the physical properties required of microbicidals?
stability under diverse environenemtnal conditions in multiple topical dosage forms
How are correlates of vaccine protection be defined?
only in the context of trials that show some protection
What is the only vaccine trial to show some protection against HIV infection?
What pre-clinical models are used to assess the potential toxicity of cytotoxicity of HIV drugs?
What preclinical models are used to assess the immune response to
mice; mini-pigs (adjuvants); non-human primate models
What does the pharmacokinetics of a drug tell you?
bioavailability; how long it stays in tissues in active forms
What are the humoral assays for vaccine success?
plasma/serum anti-env IgG and IGA binding antibody; HIV neutralisation; ADCC against virus0infected cells targets