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HIV & Infections > HIV > Flashcards

HIV Flashcards

1
Q

where is the highest HIV/AIDS population

A

sub-Saharan Africa

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2
Q

initial risk groups

A

-men who have sex with men (MSM) (account for most)
-injecting drug users
- recipient of blood products

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3
Q

what is HIV

A

human Immunodeficiency Virus
-an RNA virus which has to recode itself into a double stranded DNA to insert into a host DNA

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4
Q

how does HIV replicate

A

convert their genetic material into host genetic material via reverse transcription by viral enzyme reverse transcriptase

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5
Q

what is AIDS

A

Acquired Immune Deficiency Syndrome
- observed as Pneumocystis jiroveci (PCP) infection in homosexual men & injecting drug users

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6
Q

what is PCP

A

-rare opportunistic infection which occurs in immune compromised pts

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7
Q

what happens if HIV is left untreated

A

AIDS

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8
Q

what is HIV-2

A
  • has five phylogenetically distinct forms most common in west Africa
  • subtypes less virulent and transmissible in humans
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9
Q

what is HIV 1

A

-most commonly referred to when talking about HIV
- has 4 groups: MNOP, which represent Simian Immunodeficiency Virus (SIV) into humans

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10
Q

what is group M of HIV1

A
  • Has 9 genetic sub types (clades)
    -subtype C most common as it accounts for more than 55% of HIV1 infections
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11
Q

what is circulating recombinant forms (CRFs)

A
  • 2 subtypes meet in same host cell & share genetic code ….. most dont survive
    e.g. CFR A/E = A and a parent subtype E (not a pure E subtype)
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12
Q

can someone be infected with multiple distinct HIV1 strains

A

yes…… reported cases of people co- infected with 2+ strains
simultaneously before their immune system could react

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13
Q

what is the structure of HIV

A

-fatty membrane with 72 protein spikes made up of gp41(mediates fusion between viral and cellular membranes) and gp120 (for movement to bind to target cell)
-2 identical strands of RNA and reverse transcriptase, integrase and protease for replication

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14
Q

how does HIV replicate

A
  1. once in cell, gp120 binds to CD4 (found on T cell surface) receptors on host cells
  2. Gp120 conformational change = bind to a chemokine co-receptor (CCR5 on macrophages or CXCR4 on T helper cells)
  3. GP41 interacts with the host cell & fuse HIV particle to host
  4. HIV RNA and replication enzymes enter cell
  5. viral reverse transcriptase converts RNA to DNA in host cytoplasm
  6. viral DNA moves into host cell nuclues and becomes part of host DNA = Provirus & viral integrase facilitates this
  7. messenger RNA produced and host mRNA is used to produce viral proteins/ enzymes (translation)
  8. precursor proteins from immature core cut into smaller functional proteins by viral protease= viral particle
  9. viral particle leaves cell and is released into blood
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15
Q

what is the name of drugs that work at the stage of Gp120 conformational change

A

entry inhibitors

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16
Q

what is the name of drugs that work at the sage of HIV RNA in host and give examples

A

fusion inhibitors e.g. Enfuvirtide

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17
Q

what drugs target convertion of RNA to DNA process

A

Nucleoside non-nucleoside reverse transcriptase inhibitors

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18
Q

what drugs target integration of HIV DNA with host DNA (think enzyme involved here) & give examples

A

Integrase inhibitors:
Bictegravir
Cabotegravir
Dolutegravir
Elvitegravir
Raltegravir

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19
Q

what drugs are involved in final process of HIV replication (think of protein + enzymes involved) and give examples

A

Protease inhibitors:
Atazanavir
Darunavir
Lopinavir
Ritonavir
Tipranavir

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20
Q

what are the 4 categorise in HIV testing

A

-Third generation tests
- Fourth generation tests
- Rapid HIV tests
- Polymerase Chain Reaction (PCR) Tests

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21
Q

what are 3rd generation tests

A

-enzyme linked immunosorbent assay (ELISA) antibody test
-inexpensive, accurate and very sensitive
- disad: only become accurate after 12 weeks as takes a person 6-12 weeks to raise antibodies against HIV
-

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22
Q

what are 4th generation tests

A

-ELISA to detect antibodies and p24 antigens
- detect 1 month post exposure and possibly 11 days post
-BASHH recommend this for anyone presenting for test 4 weeks post exposure
- 4 week post exposure follow up recommended because highly infectious in 1st few weeks
-

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23
Q

what are self testing kits

A
  • work as ELISA tests
    -e.g. OraQuick HIV-1 and HIV-2 rapid test kit
    -results in 20mins
    -use blood or oral fluids sample
    -positive results = confirmatory stands ELISA test
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24
Q

what are Polymerase Chain Reaction (PCR)

A

-detects HIV genetic material
-identify HIV in blood samples within 2-3 weeks of infection
-usually used for babies born to mothers with HIV because have maternal HIV antibodies for several months after birth= false positive ELISA test
-expensive & require training

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25
Q

how often are Gay, bisexual and other men who have sex with men are advised to test

A

every 3 months or if having sex with new partner

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26
Q

what does HIV actually do

A

-attacks the immune system by destroying CD4 positive T cell (CD4 cells)
-CD4 cells co-ordinate immune responses…. destruction = vulnerable to opportunistic infections + other complications

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27
Q

which 2 parameters used to monitor progression

A

-CD4 cell count: for the health of an individual’s immune system. normal= 800 and 1500 cells/µl.
-viral load: measure of plasma HIV RNA

HIGH CD4 = LOW viral load

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28
Q

what are the 3 clinical presentations of HIV

A

primary HIV infection, chronic HIV infection and AIDS.

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29
Q

what happens during the primary infection

A

-dynamic equilibrium between virus replication and its destruction by the immune system
- viral load increase in first few months and then decreases = highly infectious
-very few symptoms
-Seroconversion (loss of antibody detectability) illness = recognisable symptoms in first 2 months
- symptoms disappear within couple weeks, when HIV antibodies start being produced by Bcells
-symptoms mistaken for flu

30
Q

what are the symptoms of primary HIV infection

A

Rash
Fever
Weight loss
Persistent lymphadenopathy
Diarrhoea for longer than four days
Malaise
Headaches

31
Q

what happens in chronic HIV

A

-remain asymptomatic for while before progression
-after diagnosis… CD4 count and viral count monitored to determine severity

32
Q

what are the non- specific symptoms of HIV

A

Rapid weight loss
Recurring fever
Profuse night sweats
Prolonged swelling of the lymph
glands
Immunosuppression related
conditions

33
Q

what happens in diagnosis of AIDS

A

-HIV infected person presents with one or more AIDS defining illnesses (opportunistic infections and
malignancies) because destruction the immune system, and prevention of normal immune
responses
- CD4 count below 200 cells/µl

34
Q

give examples of AIDS defining illnesses

A

Cryptococcal meningitis
Cytomegalovirus disease
Mycobaterium avium complex (MAC)
Pneumocystis pneumonia (PCP)
Progressive multifocal leucoencephalopathy
(PML)
Toxoplasmosis encephalitis
Tuberculosis
Cervical cancer
Kaposi’s sarcoma
Non-Hodgkin’s lymphoma
Primary cerebral lymphoma

35
Q

what are the HIV treatment goals as they do no cure it

A

-Prevention of morbidity and mortality associated with HIV
- Improving physical and psychological well-being of a person living with HIV (PLWH)
- Prevention of onward sexual transmission to others
- Prevention of maternal transmission (where applicable)
- Restoring or maintaining immune function

36
Q

what is the choice of drug based on

A

-likelihood of success against the current viral strain
-tolerability
-likelihood of patients to adhere

37
Q

how does point at which treatment is started affect life expectancy

A

-starting late can cause up to 15 years of reduced life expectancy

38
Q

when should Antiretrovirals (ART) be started

A
  • on day of diagnosis
    -if presenting with AIDS defining illness or other serious bacterial infection with a CD4 count ≤200cells/μL
    =ART 2 weeks after antibacterial chemo
39
Q

what to screen before ART regimen

A

-HIV resistance
-Hepatitis B and C co-infection
- Cardiovascular risk
- Diabetes
- Renal problems
- Psychiatric problems
- Alcohol use
- Recreational drug use

40
Q

what are the 4 possible combination first line drugs in ART

A

-Tenofovir/emtricitabine (Truvad or Descovy) with dolutegravir (Tvicay) – two tablets daily
-Abacavir/lavivudine/dolutegravir (Triumeq) – one tablet daily
- Tenofovir/emtricitabine/bictegravir (Biktarvy) – one tablet daily
-Doutegravir/lamivudine (Dovato) – one tablet daily

41
Q

when should you change ART regimens

A

when viral load starts to increase…. shows resistance

42
Q

what are the main problems with HAART regimen (highly active antiretroviral therapy)

A
  • life long
    -side effects
    -compliance issues
    -poor penetration into brain = local proliferation of virus
43
Q

give examples of Nucleoside
reverse transcriptase inhibitors (NRTIs)

A

Abacavir
Darunavir
Emtricitabine
Lamivudine
Tenofovir
Zidovudine

44
Q

give examples of Non-nucleoside
reverse transcriptase inhbitors
(NNRTIs)

A

Doravirine
Efavirenz
Etravirine
Nevirapine
Rilpivirine

45
Q

what is the MOA of NRITS

A

-become incorporated into viral DNA = act as chain terminators in HIV reverse transcriptase reaction
- dideoxy-nucloside analogues which lack a second hydroxyl group = essential addition of subsequent bases for DNA elongation
-inhibit HIV-1, HIV-2,human T-cell leukaemia/lymphoma

46
Q

what is the MOA of NNRITS

A
  • bind at a different site on reverse transcriptase and inhibit the
    movement of protein domains necessary for DNA synthesis
    -non-competitive inhibitors
    of reverse transcriptase
47
Q

what are two mechanisms of NRTI resistances

A

-increased drug discrimination: active site amino acid changes = decreased affinity of enzyme for drug
- increased rate of primer unblocking AKA offloading: combination of amino acid changes= removal of the chain terminator and replacement with a natural nucleoside (pyrophosphorylysis)

48
Q

what do NRTIS use for activation and causes toxicity & which drug least toxic

A

-use cellular rather than viral enzymes for activation to the triphosphate form
-toxicity due to the inhibition of mitochondrial DNA polymerase by the triphosphates
-Lamivudine least toxic

49
Q

Side effects of NRTIs

A

-GI disturbances (nausea, vomiting, abdominal pain, flatulence, diarrhoea)
-Anorexia
- Pancreatitis
- Liver damage (hepatomegaly with hepatic steatosis)
- Lactic acidosis
- Dyspnoea
- Cough
- Headache
-Insomnia, dizziness, fatigue,
- Blood disorders (anaemia, neutropenia, thrombocytopenia)
- Myalgia, arthralgia
- Rash, urticaria
- Fever
- Fatal hypersensitivity (with abacavir)

50
Q

side effects of NNRTIs

A

-rash within first 2 weeks of treatment (6 weeks for nevirapine)
-rash more common in women with etravirine & this drug can cause severe hypersensitivity reactions
-Potentially life-threatening hepatotoxicity in first 6 weeks of treatment with nevirapine= monitor liver function
-suicidal ideation, psychosis and severe depression with Efavirenz

51
Q

MOA for protease inhibitors

A

-prevent the release of the mature infectious virus particle from the host cell
-competitively inhibit or reduce the activity of viral protease resulting in the production of inactive viral proteins
-prevents the maturation of virioins infecting other cells
-used in HIV1 AND 2

52
Q

what causes resistance to protease inhibitors

A

-use as single agents in the treatment of HIV

53
Q

side effects of protease inhibitors

A

-same as NNRTIs and NRTIs
-also associated with hyperglycaemia = used with caution in diabetics

54
Q

interaction of protease inhibitors

A

-may be both inhibitors and inducers of CYP450…. combined use with ritonavir = change degree of inhibition/ induction
- monitor use with drugs that are affected by CYP450 conc changes

55
Q

MOA of fusion inhibitors

A

-interacts with the viral surface glycoprotein gp41= prevent fusion of viral and host cell membranes
-Enfuvirtide 36 amino acid peptide…. structurally very similar to gp41 segment
-administered by sub-cutaneous (BD)
-Enfuvirtide only licensed to treat resistant HIV infection in combination to other ARTs or for pts intolerant to other ARTs

56
Q

key counselling point for enfuvirtide

A

-how to recognize the signs and symptoms of a hypersensitivity reaction & to seek medication attention if so.

57
Q

Integrase inhibitors MOA

A
  • inhibit integrase, which stitches HIV DNA into the host cell’s DNA
    -integrase attractive target for therapy because no similar enzyme in human cells
58
Q

CCR5 inhibitors MOA e.g. maraviroc

A

-only one licensed drug in this class
-used in combination with other antiretrovirals in pts previously with ARTs
-blocks the activity of the co-receptor CCR5 on macrophages
-need for tropism assay to determine whether the infection is CCR5-trophic before treatment can be initiated

59
Q

examples of combination products

A

-Kaletra: Lopinivir/ritonavir
-Kivexa: Abacavir/lamivudine
-Truvada: Emtricitabine/tenofovir disoproxil
-Atripla: Tenofovir disoproxil/emtricitabine/efavirenz
-Eviplera: Tenofovir disoproxil/emtricitabine/rilpivirine
-Stribild: Tenofovir disoproxil/emtricitabine/elvitegravir/cobicistat
-Combivir: Zidovudine/lamivudine
-Trizivir Dascovy Genvoya
Odefsey:
Abacavir/lamivudine/zidovudine Emtricitabine/ tenofovir
alafenamide
Tenofovir alafenamide/ emtricitabine/elvitegravir/cobicistat

60
Q

what are injectable long-acting treatments 2022 & who is it recommended for

A

-cabotegravir and rilpivirine (given as two separate injections every two months)
-recommended for pts with virological suppression (HIV-1 RNA fewer than 50 copies/mL)
-must be on stable antiretroviral regimen and without viral resistance & no previous virological failure with any NNRTIs or integrase inhibitors

61
Q

PK of Zidovudine

A
  • given Oral/ IV with half life of 1hr
    -Metabolized to inactive glucuronide in
    liver
    -20% active form excreted in urine
62
Q

PK of didanosine

A
  • oral
  • half life of 1.5hrs
    -Renal clearance by glomerular filtration and active tubular secretion
  • 20% of active form excreted in urine
63
Q

PK of Emtricitabine

A

-Excreted largely unchanged in urine (some in faeces)
-half life of 10hrs

64
Q

PK of Lamivudine

A

-Excreted mainly unchanged by active renal secretion
- 5-7hrs

65
Q

PK of Stavudine

A

-Renal clearance by glomerular filtration
and active tubular secretion
- half life 1-1.5hrs

66
Q

PK of Abacavir

A
  • half life 1.5hrs
  • Hepatic metabolism primarily by alcohol dehydrogenase and by glucuronidation
    -metabolites excreted in urine
67
Q

PK of Efavirenz

A
  • half life 52-76 hrs
  • 14 to 34% of a dose is excreted in the
    urine
    -most excreted in faeces
68
Q

PK of Nevirapine

A
  • half like 45 hours (after single dose)
  • Excreted in urine as glucuronide conjugates of the hydroxylated metabolites
69
Q

PK of rilpivirine

A

-45 hours half life
-Primarily metabolized and eliminated in Liver
- 25% in excreted unchanged in the faeces

70
Q

pk of protease inhibitors

A

-mainly eliminated in faeces as metabolites

HIV & Infections (4 decks)

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