Approaches towards a cure for HIV Flashcards
(36 cards)
Why is a cure for HIV needed?
needs to be provided lifelong; global instability of funding etc; ART drug resistance; ART toxicity
Where is the HIV reservoir focused?
lymphoid tissue; lymph nodes; GALt; GU tract and brain
What are the ways of measuring HIV reservoir?
total HIV DNA; 2-LTR circles; integrated DNA infecitous units
How does the integrated DNA infectious units assay work?
activate cells and see if they can replicate virus
What is the problem with the total HIV DNA assay?
doesn’t reflect replication competent virus but is still the most reproducible measure used in many studies
What is the most clinicalyl important outcome for HIV remission/cure?
viral control off ART
What are the ways of measuring viral control off ARt?
time to viral rebound; allow viral rebound and look fro length of potential control; allow to reach a new set point
When does viral rebound usually happen after ART interruption?
within 7-30 days
What are the questions surrounding ART interruption study designs?
how to do it safely; how frequently to test viral load; how to test viral load; risks of viral transmission; how long to wait before treatment re-initiation
What is a functional cure?
host control of viral replication without continued treatment; immune function restored and stabilised; HIV-induced inflammation reduced; risk of transmission to others reduced
What are hte 4 main approaches to cure HIV?
inhibit residual replication; immune modulation; shock and kill; gene therapy
What is the goal of inhibiting residual replication?
limiting the size of HIV reservoir below a threshold- enhanced cART and tissue penetration
What is the gaol of immune modulation strategy?
make the immune response able to recognise and remove HIV infected cells
What are the methods of immune modulation?
therapeutic vaccine; broadly neutralising antibodies
What is the strategy with gene therapy?
modify gene expression of latently infected cells to either lock down viral transcription or kill HIV infected reservoir cells
What have been the results of intensifying ART by additional ART agents?
after adding CCR5 inhibitor no impact on total HIV DNA; no impact with adding extra ART
What is the hypothesis with starting ARt in acute infection?
HIV reservoir in acute infection is most homogenous, smallest size and maybe easiest to influence
What is the result of initiating ART acutely vs in chronic infection?
rate of decline in total HIV DNA is nehanced after starting ART when started in acute infection and absolute level of total DNA achieved on stable therapy is lower
What does total HIV DNA predict?
time to viral rebound after treatment interruption
What is thought to be the reason for very early ART initiation not conferring post treatment control?
in Thai study, 8 individuals started in first 2 weeks of infection did not have any improved PTC- maybe as prior to antibody development, which didn’t allow the immune system to develop and be able to control viral rebound
what is the prupose of giving anti-PD1 to treat HIV patients
prevents immune exhaustion
What is the hypothesis behind broadly neutralising antibodies reducing HIV reservoirs?
block cell-cell spread of HIV; promote ADCC; antibody-dependent phagocytosis and complement fixation; antibody-antigen compelxes activate DCs to enhance antigen presentation function
What have been results of therapetuic T cell vaccine studies?
have had no impact on the HIV reservoir or lower viral rebound after ARt interruption
What is the theory behind DC-primed vaccines?
monocyte derived DCs loaded ex vivo with RNA encoding HIV antigens as are potent APCs and induce T cells reponses- has been successful in chronic infections and acancer
