Approaches towards a cure for HIV Flashcards Preview

Module 2 > Approaches towards a cure for HIV > Flashcards

Flashcards in Approaches towards a cure for HIV Deck (36):

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


What was the result of DC-primed vaccination?

rapid viral rebound after vaccination and aRT interruption


What are the 5 key bNAb binding sites on the HIV envelope?

Cd4-binding site; V1/V2; V3; gp120/gp41 interface and MPER


What happened when Bnabs were given to viraemic patients prior to starting ARt?

acted as antivirlas and reduced HIV viral load by 2.5 logs


What was the effect of giving Bnabs to patients during treatment interruption?

up to 19 week delay in rebound vs historical avergae of 2.6 weeks


what caused rebounds in patients given bnabs during treatment interruption?

escape variants or once antibody levels had dropped


What is the hypothesis with latency reversing agents?

force viral transcription from latently infected cells to induce cell death and reduce the size of hte reservoir


How do histone deacetylases inhibit HIV expression?

catalyse de-acetylation of histone tails and keep chromatin in a compacted state, inhibtion of these histone deacetylases promotes histone acetylation leading to relaxation of chromatin and initiation of transcription


Give an example of a histone deactylase inhibitor?



What were the resutls of a study comparing ART vs ART+ vorinostat +HIV vaccine?

no difference in total HIV DNA or viral outgrowth


What provides hope for the kick and kill approach?

study in rhesus monkeys with a TLR7 agonist and V3 bnab substantially delayed and controlled viral replication after cessation of ARt


What is the novel gene-editing technique capable of disrupting HIV-integrated genomces?

CRISPR-Cap9 technique


What is a danger with gene editing?

what is the possibility of deleting the wrong genes?