19. HIV Agents Flashcards
burst of viral antigen > CD4 T cells decline > anti-HIV antibody gp120 increases > opportunistic infection
clinical progression of HIV disease
attachment > fusion > reverse transcription > integration > genome replication > budding > protein cleavage > mature virion
human immunodeficiency virus life cycle
inhibit attachment
co-receptor antagonist
inhibit fusion
fusion inhibitors
inhibit reverse transcription
nucleoside reverse transcriptase inhibitors / non-nucleoside transcriptase inhibitors
blocks integration
integrase strand transfer inhibitors
blocks protein cleavage
protease inhibitors
combination of two or three antri-retroviral drugs, from at least two different classes
standard of care for HIV therapy
abacavir, lamivudine, tenofovir disproxil fumarate, tenofovir alafenamide, emtrictiabine
nucleoside reverse transcriptase inhibitors
efavirenz, doravirine, rilpivirine
non-nucleoside reverse transcriptase inhibitor
darunavir, ritonavir, atanzanavir
protease inhibitors
bictegravir, raltegravir, dolutegravir
integrase strand inhibitors
enfuvirtide
fusion inhibitor
maraviroc
co-receptor antagonist
2 NRTI antivirals + 1 INSTI inhibitor
recommended initial treatment for HIV
1 NRTI + 1 INSTI
new two drug regiment for HIV
act at the active site of reverse transcriptase, require cellular kinases to converted to triphosphate form, approved for chronic hepatitis B, mitochondrial damage
NRTIs
associated with lipodystrophy syndrome
zidovudine and stavudine
cytosine analogue, single base change confers high level resistance, included in recommended initial treatment, can be used for heptatis b
lamuvidine
flourinated analogue of lamivudine, longer half life, headache, nausea, diarrhea, resistance by single base pair change, recommended in initial treatment regiment for HIV
emtricitabine
guanosine analogue, hypersensitivity in 4% of patients leading to fever, skin rash, fatigue, GI symptoms, associated with HLA-B5701, genetic screening must be done prior to treatment, resistance by multiple mutations, used in recommended initial treatment regimen
abacavir
prodrug of tenofovir, analogue of adenosine, crosses the placenta, recommended for initial treatment, contraindicated in renal patients
tenofovir disoproxil fumarate
phosphonoamidate prodrug of tenofovir, metabolized intracellularly by cathepsin A, higher concentrations in HIV replicating cells so more specific, bone and kidney toxicities
tenofovir alafenamide
acts on integrase enzyme
integrase inhibitors
analogue integrase strand transfer inhibitor, safe, resistance by single mutation
raltegravir
integrase strand transfer inhibitor, nausea, diarrhea, headache, recommended initial treatment of HIV
bicetegravir
integrase strand transfer inhibitor, combined with antiretroviral therapy in a single pill, insomnia, headache, still works if resistance against raltegravir and elvitegravir, increased risk of neural tube defects, contraindicated in pregnancy
dolutegravir
boosted PI + 2 NRTIs, NNRTI + 2 NRTIs, INSTI + 2 NRTIs
recommended initial regimens in certain clinical situations - 2020
target HIV protease by mimicing a peptide blocking maturation after budding, multiple mutations necessary for high level resistance
protease inhibitors
non-peptidic protease inhibitor, given orally, coadminstered with pharmokinetic enhancer, skin rash, GI intolerance, headache, 90% are still susceptible, recommended initial regimen for HIV
darunavir
peptide, once daily oral administration, requires acid for absorption so no antiacids, inhibitor of CYP3A4 and CYP2C9, multiple codon changes for high level resistance, included in recommended initial treatment for HIV
atanzavir
peptidomimetic protease inhibitor, 1st of its class approved, given orally, most commonly used as pharmacokinetic booster, potent inhibitor of CYP3A4 and 2D6s, multiple mutations for high level resisance, recommended in initial treatment of HIV
ritonavir
pharmacokinetic enhancer, inhibits CYP3A enzymes, no antiviral action on it’s own
cobicistat
target reverse transcriptase, do not require phosphorylation, not active against HIV-2, single amino acid changes confer resistance
reverse transcriptase inhibitors
non-nucleoside reverse transcriptase inhibitor, orally adminstered, induces CYP3A4s, associated with birth defects during pregnancy
efavirenz
non-nucleoside reverse transcriptase inhibitor, given orally, CYP3A4 substrate, resistance to this drug can confer resistance to other NNRTIs
doravirine
non-nucleoside reverse transcriptase inhibitor, administered orally, contraindicated with proton pump inhibitors, single base change confers resistance, recommended initial regimen in HIV treatment
rilpivirine
drugs reserved for treatment experienced patients
CCR5 receptor antagonists,
blocks co-receptor binding
CCR5 receptor antagonists
co-receptor antagonist, given orally, resistance through changes in tropism or mutations in gp120 blocking binding to it, resistance also by HIV virions that enter through CCR4 pathway instead, screen for tropism before use
maraviroc
blocks virus envelope fusion with plasma membrane, blocks confirmational change of gp41 preventing binding to gp120 by binding to prefusion complex
fusion inhibitors
36 amino acid peptide fusion inhibitor, administered in twice daily subcutaneous injection, painful erythematous nodule at the site of infection, high level resistance requires multiple mutations in gp41 gene
enfuvirtide
combination of TDF and emtricitibine, recommended for individuals in certain high risk groups for HIV infection like HIV negative individual with HIV positive partner, commericial sex workers, injection drug users, assess pregancy if women are pregnant
pre-exposure prophylaxis for HIV
recommended in groups like blood transfusion, needle sharing during injection drug use, percutaneous needlestick, within 72 hours of exposure, 28 day treatment, similar 3 drug regiment as preferred combination antiretroviral therapy for initial therapy for most people with HIV, testing for HIV is included in management
post-exposure prophylaxis
