Pre-clinical models of HIV prevention

Question 1

what are the methods of HIV prevention prior to exposure?

Answer 1

behaviour changes; STI treatment; male circumcision; PrEP; vaccines

Question 2

What are the methods of HIV prevention at the time of exposure?

Answer 2

male and female condoms; lube; cervical barriers; microbicides (vaginal and rectal PrEP)

Question 3

What is the function of pre-clinical models of HIV?

Answer 3

facilitate and accelerate prioritization of candidate prevention agents ; their combinations, dosing and formulations to be evaluated in large trials

Question 4

Why is the rectal epithelium particularly vulnerable to HIV infection?

Answer 4

single layer of columnar epithelium which is easily damaged; intestinal lamina propria contains an abundance of highly activated target cells for HIV-1 infection

Question 5

What are some of the special considerations for the design of preventive strategies at hte mucosal level?

Answer 5

some ARVs may be cytotoxic in the colorectum or may induce immunological toxicity- induce reponse favourable for HIV

Question 6

What does the cellular model of a co-culture of DCs and PM-1 (Cd4 T cell clone) allow the study of?

Answer 6

mimicks DCs-T cells interaction during viral amplification of the founder population and viral dissemination

Question 7

What is hte function of the cellular models using epithelial cell lines and primary cells?

Answer 7

assess potential cytotoxicity, disruption of petihleium integrity induced by the candidate microbicide

Question 8

What is the general function of the cellular models?

Answer 8

very good at screening for microbicides

Question 9

What are the types of mucosal tissue explants?

Answer 9

cervical, vaginal, penile and colorectal which can be polarised or non-polarised

Question 10

What can be measured from mucosal tissue explants?

Answer 10

virus in supernatant; proinflammatory cytokines and drug concentration in tissue

Question 11

What are the limitations of non-human primate models of HIV?

Answer 11

cost; HIV does not replicate efficiently in macaque cells

Question 12

What other viruses can be used in non-human primate models?

Answer 12

SIV or SHIV- with HIV env or RT

Question 13

What are hte problems with humanised mice models?

Answer 13

cannot be bred; don’t recapitulate basic features of HIV pathogenesis; don’t elicit B cell responses upon vaccination

Question 14

What are the physical properties required of microbicidals?

Answer 14

stability under diverse environenemtnal conditions in multiple topical dosage forms

Question 15

How are correlates of vaccine protection be defined?

Answer 15

only in the context of trials that show some protection

Question 16

What is the only vaccine trial to show some protection against HIV infection?

Answer 16

RV144

Question 17

What pre-clinical models are used to assess the potential toxicity of cytotoxicity of HIV drugs?

Answer 17

rodents

Question 18

What preclinical models are used to assess the immune response to
vaccine/drug?

Answer 18

mice; mini-pigs (adjuvants); non-human primate models

Question 19

What does the pharmacokinetics of a drug tell you?

Answer 19

bioavailability; how long it stays in tissues in active forms

Question 20

What are the humoral assays for vaccine success?

Answer 20

plasma/serum anti-env IgG and IGA binding antibody; HIV neutralisation; ADCC against virus0infected cells targets

Question 21

What are the cellular assays of vaccine success?

Answer 21

intracellular cytokine staining; ELISPOT; cellular proliferation in response to vaccine antigens