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HIV Flashcards

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1
Q

What are examples of human retroviruses?

Retriviral DNA exists in human genome as product of evolution. Does not produce infectious virus

A 
Family - retrovirus
Sub-family - orthoretrovirinae
Genus - lentivirus
Species -
HIV1 
HIV2 - West Africa, less virulent

Family - retrovirus
Sub-family - orthoretrovirinae
Genus - deltavirus
Species - HTLV1/ HTLV2 - West Indies/ Japan.

Also known has tropical spastic paraparesis. T- cell leukaemia

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2
Q

What is structure of HIV virus

A

GP41/ GP120 envelope glycoproteins
Lipid mebrane - host derived
Matrix protein p17

Single stranded RNA
RT
Integrase
Virion core proteins - p7, p9, p 24

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3
Q

HIV nuclear material is two copies of positive sense SS RNA.

It codes for virion proteins/ regulatory proteins.

What virion proteins does it code for?

A

LTR

gag

pol

env

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4
Q

HIV nuclear material is two copies of positive sense SS RNA.

It codes for virion proteins/ regulatory proteins.

What regulatory proteins does it code for?

A

nef

rev

tat

vif

vpr

vpu

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5
Q

What do these HIV virion proteins code for?

LTR

gag

pol

env

A

LTR - long terminal repeat promotes transcription/ replication

gag - virion core proteins -

  • p7
  • p9
  • p17 - matrix
  • p24 - nucleocapsid

pol - RT, integrase, protease

env - gp160 glyocprotein which is cleaved into gp120 and gp41

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6
Q

gp 41 and gp 120 formed from env gene.

What are their roles?

A

gp 120 - attachment protein

gp 41 - fusion protein

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7
Q

What do these HIV regulatory proteins code for?

nef

rev

tat

A

nef - negative regulatory factor - important for virulence

rev - promote export viral RNA from nucleus

tat - transactivator protein regulates viral transcription

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8
Q

What do these HIV regulatory proteins code for?

vif

vpr

vpu

A

What do these HIV regulatory proteins code for?

vif - virion infectivity factor

vpr - weak transcriptional activator

vpu - for efficient budding

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9
Q

What is replication cycle of HIV?

A 
Absorption of HIV gp120 onto CD4 cell
Fusion via GP41
Penetration
Uncoating
Reverse transcription of positive sense ssRNA into DNA
Integration into host DNA - now provirus

Transcription of viral mRNA and progeny RNA
Translation of viral proteins
Assembly of virions
Budding via envelope proteins

HIV also binds to dendritic cells/ macrophages, which transport to lymph nodes, which helps spread infection to other CD4 cells

Most CD4 cells die. Only few survive to continue HIV virion production

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10
Q

HIV-2 confined to West Africa, originally zoonosis from sooty mangabeys

HIV-1 has different groups, what are they?

A

During transmission from chimpanzees, groups evolved.

M - major. 90% of cases, worldwide distribution. Emerged between 1910-1930 in West Africa
N - new. West Africa. Very rare
O - outlier. West Africa
P - only one case ever

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11
Q

HIV1 group M (major), has further subtypes, based on geographical spread. What are they?

A

Subtype A: Central and East Africa, Eastern Europe

Subtype B: West and Central Europe, the Americas, Australia, South America, and several southeast Asian countries (Thailand, and Japan), as well as northern Africa and the Middle East. Most common in UK

Subtype C: Sub-Saharan Africa, India, and Brazil.

Subtype D: North Africa and the Middle East.

Subtype F: South and southeast Asia.

Subtype G: West and Central Africa.

Subtypes H, J, and K: Africa and the Middle East

CRF - circulating recombinant types, due to recombination between different subtypes

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12
Q

HIV virus uses gp120 to bind to CD4 receptor on which cell types?

A 
T-helper cell
Monocyte
Dendritic cell
Langerhans cell
Microglia
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13
Q

HIV virus binds gp120 to CD4. What other receptors are required for entry?

A

chemokine co-receptor CCR5 absolutely required
CXCR4 co-receptor is also desired by virus

If CCR5 gene deletion, host can be resistant to HIV progression- elite controllers 0.3%.

Once infected Th rests in lymphoid tissue, it can continue to produce new virions. If Th cell becomes activated, cell will die.

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14
Q

What is immune response to HIV infection?

A

CD8 T cells which kill infected cells
B cells produce antibodies directed towards infected cells

CD4 Th cells directly killed by virus, undergo apoptosis, damaged by CD8/ B cells

As Th count decreases, immune response wanes, and HIV load rises

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15
Q

Why does having another STI increase risk of HIV transmission?

A

Other STIs cause genital ulcers/ discharge, which can provide route for HIV transmission

Uncircumcised males more likely to be affected

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16
Q

What are transmission routes of HIV?

A

Blood transfusion - haemophiliacs
IVDU/ tattoo/ accupuncture/ needlestick
Sex

Vertical - up to 50% of HIV mothers will pass on to children (if untreated). Avoid breast-feeding, perform C-section

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17
Q

What are initial symptoms of HIV infection?

A

fever
malaise
maculopapular rash
lymphadenopathy

Can invade CNS and cause self-limiting aseptic meningitis

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18
Q

After initial HIV exposure, what tests can be used to diagnose HIV, and when are they used in timeline?

Can also perform genome sequencing to assess antiretroviral drug resistance and tropism (CCR5/ CXCR4)

A

p24 antigen - 1-8 weeks after exposure, then levels will drop as Ab produced

HIV antibody - 4 weeks 95% will test positive. If negative, can check up to 12 weeks after exposure

Diagnosis is infants is difficult as passively acquired IgG will be detected up to 12 months after birth. Test infant at various intervals from 12-24 months

Tests available:
p24 antigen
HIV RNA
HIV proviral DNA - check mother will always remain positive
HIV antibody
Point-of-care tests - less sensitive/ specific

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19
Q

How is HIV viral load measured?

A

RT-PCR of HIV RNA

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20
Q

AIDS is when:

  • patient with HIV antibodies
  • develops opportunistic infections (usually CD4 <200)

What are viral opportunistic infectious?

A

CMV - retina, brain, GI

HSV - lungs, GI, CNS, skin

JC - brain PML

EBV - hairy leukoplakia, primary cerebral lymphoma

HHV8 - Kaposi sarcoma

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21
Q

AIDS is when:

  • patient with HIV antibodies
  • develops opportunistic infections (usually CD4 <200)

What are bacterial opportunistic infectious?

A

Mycobacterium tuberculosis - disseminated/ extrapulmonary

Mycobacterium avium

Salmonella dissemninated

Also higher risk of common bacterial pathogens - streptococcus/ haemophilus

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22
Q

AIDS is when:

  • patient with HIV antibodies
  • develops opportunistic infections (usually CD4 <200)

What are protozoal/ fungal opportunistic infectious?

A

Cryptococcus neofromans - CNS

Coccidioides

Histoplamosis

PCP

Toxoplasma

Cryptosporidium

Isospora

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23
Q

What are ways to reduce HIV spread?

Combatting HIV/ AIDS was 6th Millenium Development Goal

A

Change sexual behaviours - condoms

Pregnant women start ART after first trimester

Treat other STIs

Clean needles

Blood product screening

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24
Q

HIV transmission can be explained via R0 equation. What are factors in this?

R0 >1 epidemic spread can occur
R0 <1 infection will eliminate

A

R0 is proportional to C x beta x D

C - is the average rate of contact between susceptible and infected
individuals

beta - transmissibility - probability of HIV transmission per given exposure e.g anal intercourse has 1.65 % risk transmission

D - duration of infectious period

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25
What are risk factors for more rapid progression of HIV?
``` Female Older Depression Poor pre-morbid nutritional state Certain HLA types Co-infection HBV/HCV/ TB can alter immune system ```
26
WHO HIV staging is grouped into: Primary HIV infection Clinical stage 1 - asymptomatic Clinical stage 2 - mild symptoms (CD4 <500) Clinical stage 3 - moderate symptoms (CD4 200-500) Clinical stage 4 - severe symptoms (CD4 <200) On average, untreated it will take 8-10 years from HIV acquisition to AIDS. WHO staging does not use CD4 count What symptoms might primary/ clinical stage 1 have?
Asymptomatic - time from acquisition of virus, to development of HIV antibody, HIV p24 antigen or HIV RNA Viral illness - fever, malaise, sore throat, lymphadenopathy, maculopapular rash - approx 50% of patients
27
WHO HIV staging is grouped into: Primary HIV infection Clinical stage 1 - asymptomatic Clinical stage 2 - mild symptoms Clinical stage 3 - moderate symptoms Clinical stage 4 - severe symptoms What symptoms might primary/ clinical stage 2 have?
``` Moderate weight loss - <10% body Recurrent URTI VZV Angular chellitis Recurrent oral ulceration Sebhorrhoeic dermatitis Fungal nail infections ```
28
WHO HIV staging is grouped into: Primary HIV infection Clinical stage 1 - asymptomatic Clinical stage 2 - mild symptoms Clinical stage 3 - moderate symptoms Clinical stage 4 - severe symptoms What symptoms might primary/ clinical stage 3 have?
Unexplained weight loss >10% body Chronic diarrhoea - two or more loose stools per day Persistent oral candidiasis Oral hairy leukoplakia Pulmonary TB Severe bacterial infections - pneumonia, meningitis
29
WHO HIV staging is grouped into: Primary HIV infection Clinical stage 1 - asymptomatic Clinical stage 2 - mild symptoms Clinical stage 3 - moderate symptoms Clinical stage 4 - severe symptoms What symptoms might primary/ clinical stage 4 have?
``` HIV wasting syndrome - >10% weight loss and diarrhoea PCP Recurrent severe bacterial pneumonia Oesophageal candidiasis Extrapulmonary TB KS CMV Toxoplasmosis HIV encephalopathy Cryptococcus Cryptosporidiosis Isosporiasis Coccidiomycosis Histoplasmosis Non-typhoidal salmoneall Lymphoma - cerebral or B-cell non Hodgkin Cervical carcinoma HIV neuropathy ```
30
What are the UNAIDS 90-90-90 targets?
90% living with HIV, know their status 90% diagnosed with receive ART 90% on treatment will have suppressed viral loads
31
What is U=U in regards to HIV?
Undetectable viral load = transmissible Data on 58 000 episodes of unprotected sex in HIV individuals, showed no transmission
32
Patient presents 8 weeks after unprotected sex, with fever, sore throat. HIV p24 positive HIV antibody negative What steps should you take next
Diagnosis is primary HIV infection Need to refer to HIV specialist and start ART within 2 weeks Early ART is associated with better preservation of immune function, CD4 count, morbidity associated with high viraemia, and reduced risk of transmission. It may also prevent HIV developing a reservoir in deep lymph nodes.
33
If initial HIV test positive, what are next steps labs take to confirm this?
Initial diagnosis on Architect Use same sample to confirm on VIDAS New sample to confirm on Archiect Geenius to check HIV1/HIV2 as different treatment Viral load by PCR Whole genome sequencing for resistance pattern
34
After initial HIV diagnosis, baseline laboratory tests are required. HIV related/ other infectious/ metabolic What are HIV related tests?
Confirm HIV1/HIV2 Viral load Genotypic resistance testing CD4 T cell count Viral tropism test is sometimes performed, if considering CCR5 inhibitor as first line therapy If PCP - consider G6PD if needing dapsone/co-trimxoazole/primaquine as contraindicated otherwise. African/ mediterranean/ Chinese
35
After initial HIV diagnosis, baseline laboratory tests are required. HIV related/ other infectious/ metabolic What are other infectious agents to test for? viral/ bacterial/ protozoal
Viral HAV IgG HBV surface antigen/ core antibody HCV IgG EBV/ CMV - serology initially, but can be negative in HIV. Check viral load buy PCR Measles IgG - if no history of vaccine/ infection Varicella IgG - if no history of vaccine/ infection Rubella IgG - in women of child-bearing age Note - vaccine preventable diseases - HAV/ HBV/ Measles/ varicella/ rubella Bacteria Chlamydia NAAT Gonorrhoea NAAT Syphilis serology IGRA Sputum for AAFB - BAL ``` Protozoa/ fungal CrAg Toxoplasmosis Strongyloides Giardia Beta-d-glucan/ galactomannan ``` Must screen partner/ children
36
After initial HIV diagnosis, baseline laboratory tests are required. HIV related/ other infectious/ metabolic What metabolic tests are required?
``` FBC U+Es LFTs Bone Lipids Glucose ``` Urinalysis Urine PCR - if proteinuria Pregnancy test HLA-B*57:01 - if abacavir being considered
37
When do perform HIV resistance testing?
At baseline At commencement of ART if there is a delay Suboptimal viral load response to therapy - <1 log10 drop in 4 weeks Virological failure - viral load >200 copies/ml on two samples while on ART. Always perform whilst on ART - as otherwise resistant strain will become smaller part of opulation On CSF samples if CSF viral load detectable on therapy Pregnancy - if detectable viral load at week 36 of pregnancy If on CCR5 antagnoist, and has virological failure, check tropism to ensure no tropism switch
38
Pregnant women with HIV, starting ART. When should repeat viral load be measured?
``` Baseline 2-4 weeks after starting ART (first trimester) Second trimester 36 weeks (third trimester) Time of delivery ```
39
Children born to HIV infected mothers. When should HIV testing be performed?
HIV proviral DNA or RNA PCR - - Within 48 hours of birth - 6 weeks of age - after completing 4 weeks anti-retroviral prophylaxis - 12 weeks of age - two months after completing prophylaxis - Monthly if breastfeeding is taking place, to detect late transmission HIV antibody testing - - 18 months - following loss of maternal antibodies at this time - 6 weeks after stopping breastfeeding
40
What are elite controllers? What are negatives to this?
Have HIV antibodies, but no HIV RNA in blood, and normal CD4 count. Usually lacking CCR5 gene, so HIV cannot bind Studies show they are in low grade inflammatory state, and may have more issues with illness compared to those on ART
41
When must HIV post-exposure prophylaxis be taken?
Within 72 hours of exposure
42
Patient commenced on ART, 4 weeks later viral load has not dropped by 1log10. Resistance testing initially negative What is the next step?
Check medication compliance/ drug side effects Re-check HIV resistance testing. Testing can detect resistant species if make up 25% of virus population. So if <25% of population, will not be detected. Once ART given, these resistant strains can emerge, and become dominant population, which can be detected.
43
When checking CD4 count and viral load, how often do you need to check CD4 count?
If patient has CD4 count >350, on two occasions, with low viral load, then no longer need to check. As we can presume CD4 will be higher than this. Re-check if new symptoms, or signs of treatment failure.
44
When should ART be initiated?
Within two weeks from diagnosis, regardless of CD4 count Hold if TB meningitis
45
What classes of ART exist?
NRTI - nucleoside/ nucleotide reverse transcriptase inhibitor NNRTI - non-nucleoside reverse transcriptase inhibitor Protease inhibitor Fusion inhibitor INSTI - integrase strand transfer inhibitors
46
How do NRTIs work?
Act as false nucleotides (ATCG) RT attempts to convert viral RNA into DNA, but NRTI inserts and causes chain termination
47
What are examples of NRTIs?
``` Abacavir (ABC) Emtricitabine (FTC) Lamivudine (3TC) Stavudine (d4T) Tenofovir (TDF) Zidovudine (ZDV) - sometimes known as AZT ```
48
How do NNRTIs work?
Non-competitive inhibitors of RT, by binding to allosteric site on enzyme HIV-2 naturally resistant
49
What are examples of NNRTIs?
Efavirenz (EFZ) Nevirapine (NVP) Rilpivirine (RPV)
50
How do protease inhibitors work?
Inhibit protease enzyme preventing cleavage of essential proteins (gag proteins) necessary for viral maturation and budding from cell membrane
51
What are examples of protease inhibitors?
Atazanavir (ATZ) Darunavir (DRV) Lopinavir (LPVr) All are prescribed with ritonavir which boosts action
52
How do fusion inhibitors work? What is an examples of this? - CCR5 inhibitor - fusion inhibitor
CCR5 inhibitor -Interfere with binding/ fusion of virus to cell membrane through co-receptor CCR5. Virus can switch from CCR5 to CXCR4 - so tropism assay is required prior to starting this class -Maraviroc (MVC) Fusion inhibitor - binds to GP41 on CD4, preventing HIV binding - Enfuvirtide (ENF, T-20)
53
How do INSTI - integrase strand transfer inhibitors work?
Inhibit viral enzyme integrase, which is essential for integration of viral DNA into host cell DNA
54
What are examples of INSTIs?
Dolutegravir (DAG) Raltegravir (RAL) Elvitegravir (EVG) + cobicistat (COBI) cobicistat is a PK (pharmacokinetic enhancer), which blocks breakdown of other drug
55
HAART is usually made of 3 drugs. Two NRTIs + third drug (NNRTI/ PI/ INSTI) 2xNRTIs are normally fixed drug combinations. What drugs make up these combinations - Truvada Descovy Kivexa Combivir
Truvada - tenofovir disoproxil fumarate (TDF) + emtricitabine Descovy - tenofovir alafenamide (TAF) + emtricitabine Kivexa - abacavir + lamivudine. Recommended only if viral load < 100 000, or any level if used with dolutegravir Combivir - Zidovudine + lamivudine
56
When is tenofovir contraindicated? When is abacavir contraindicated? When is efavirenz contraindicated?
If CrCl <70ml/min If HLA-B*57:01 positive Mental health disorder
57
What are examples of third drug added to 2xNRTIs backbone for HAART? NNRTI
NNRTI - Nevirapine Efavirenz Rilpivirine - only if viral load <100 000
58
What are examples of third drug added to 2xNNRTIs backbone for HAART? PI
``` PI - atazanavir/ ritonavir atazanavir/ cobicistat darunavir/ ritonavir darunavir/ cobicistat ``` PI interact with PPIs. So switch omeprazole to ranitidine
59
What are examples of third drug added to 2xNNRTIs backbone for HAART? INT
INSTI - Dolutegravir Raltegravir Elvitegravir + cobicistat
60
When starting ART, when do blood tests need to be monitored?
2 weeks post ART - metabolic tests to ensure no reaction 4 weeks post ART - viral load/ CD4 - expect two-log VL drop 6 months - VL should be undetectable Once established on ART - check VL every 6 months, and CD4 once a year
61
Patient has HIV and HBV. What are treatment options?
Tenofovir + emtricitabine is recommended NRTI backbone
62
Patient has HIV and HCV What are treatment options?
ART If CD4 count ok, treat HCV first, then HIV, to reduce drug-drug interactions
63
Pregnant women, when should be commenced on ART? If presenting late, treatment should be started immediately. What are options?
Prior to 24 weeks Combination - Zidovudine/ lamivudine Raltegravir Nevirapine - stat dose
64
Why do ART drugs affect liver function/ have multiple itneractions?
All metabolised via cytochrome p450 pathway
65
If patient on NRTI + NNRTI, and is failing, what is next step?
Switch to NRTI + PI
66
Patient with TB and HIV. After waiting 2 weeks, what drugs should be started?
RIPE for TB (not need to switch to rifabutin) ART - abacavir + lamviduine + dolutegravir
67
What is given to protect against opportunistic infections PCP in HIV?
Co-trimoxazole 480mg OD Co-trimoxazole 960mg M/W/F Dapsone Pentamidine nebuliser Co-trimoxazole is preferred, as also protects against diarrhoeal disease, and some effect against toxoplasma Prophylaxis can be stopped if CD4 >200 for 3 months, with undetectable viral load
68
What advice is given to avoid toxoplasmosis? If CD4 <50, how often retinal screening for CMV?
Avoid raw meat/ cat litter Every 3 months
69
PCP can present with SOB, fever, fatigue. SOB worsens quickly on exertion - can check patients saturations. Normal CXR does not exclude PCP. PaO2 <9.3 or Sp02 <92% - severe infection How to diagnose PCP?
Sputum analysis - either induced sputum/ BAL. Grocott methenamine silver stain. PCP stays in samples up to 10 days after starting treatment, so do not delay treatment awaiting diagnosis
70
What is first line treatment of PCP?
Co-trimoxazole for 21 days Oral if mild IV if severe Alternatives: Atovaquone Clindamicin + primaquine Pentamadine IV Steroids if severe. Prevents IRIS to dead fungi. Prendisolone 40mg BD 5 days Prednisolone 40mg OD 5 days Prednisolone 20mg OD for next 11 days Can take 7 days before seeing response
71
When is second line PCP treatment required? What is the treatment?
Clinical failure to first line - no improvement after 5 days (remember to consider alternative diagnosis) Sulpha allergy Patient toxicity Clindamicin/ primaquine Pentamidine IV Trimethoprim/ dapsone Atovaquone
72
What is treatment for toxoplasmosis? Often have ring-enhancing lesion on CTB Retinal exam shows retinitis
Sulphadizine + pyrimethamine Give with folinic acid 6 weeks treatment, then lower dose long term prophylaxis Anti-epileptics may be required Second line - clindamicin + pyrimethamine co-trimxazole
73
What are side effects of sulphadiazine used to treat toxoplasmosis?
Cause crystal uropathy and renal dysfunction - need to be hydrated
74
Cryptococcal meningitis causes raised ICP by preventing CSF reabsorption. When performing LP, how much fluid is removed?
Aim closing pressure <20cm H2O Or if very high, aim for half the pressure. e.g 50cm H2O aim 25cm H2O Daily LP may be required. If persistingly high pressure, or hydrocephalus, will need shunt/drain ventriculo-peritoneal shunt (if hydrocephalus) lumbar-periotenal shunt external lumbar drainage
75
How to diagnose cryptococcal infection?
Serum CrAg CSF CrAg India ink staining
76
What is treatment for cryptococcal infection?
Liposomal amphotericin + flucytosine for 2 weeks, then High dose fluconazole 10 weeks Normal dose fluconazole long term prophylaxis
77
Which organs can CMV affect?
Retina - 75% cases Lungs GI CNS
78
What eye symptoms does CMV cause? How does it appear on fundoscopy?
Reduced visual acuity, can lead to blindness Necrotising retinitis - pizza pie appearance
79
How to diagnose CMV infection?
Fundal exam CMV DNA titre does not necessarily indicate organ disease, if no symptoms. But DNA levels useful for monitoring response to treatment.
80
What are treatment options for CMV infection?
oral valganciclovir 900mg BD for 2-4 weeks 900mg maintenance until CD4 >100, and VL <40 IV options - ganciclovir foscarnet cidofovir Intravitreal anti-CMV treatment injections can be used
81
Mycobacterium avium complex is a group of common environmental organisms (mycobacterium avium and mycobacterium intracellularae). Cannot be spread person-person. Found in water, soil, dust Causes non-specific symptoms such as night sweats, fever, diarrhoea. Typically patiets CD4< 50. How is MAC diagnosed?
Sputum culture 98% diagnosed if two sets of blood cultures taken for mycobacterium culture
82
What is treatment for MAC?
Clarithromycin + ethambutol Rifabutin is added in severe cases Treat until at least symptom free for 3 months, and CD4 >100 May require lifelong treatment
83
What are patterns of disease causes by MAC?
Pulmonary MAC - usually underlying lung disease Disseminated MAC - AIDS patient, any organ Lymphadenitis MAC - children with immunodeficiency causes swelling of lymph nodes
84
What is treatment for - oral candidiasis genital candidiasis oesophageal candidiasis candidaemia
oral candidiasis - nystatin genital candidiasis - clotrimazole oesophageal candidiasis - oral fluconazole candidaemia - IV fluconazole Candida albicans is most common fungus. Other species such as C krusei or C glabrata are resistant to fluconazole, and need itraconazole
85
Stage 4 AIDS - what are causes of diarrhoeal disease? Lymphoid tissue in gut has high levels of CD4 lymphocytes - so high risk GI disease
Cryptosporidia - nitazoxanide/ paromomycin Cyclospora - co-trimoxazole Isospora belli – co-trimoxazole Microsporidia – albendazole ART side effects - particularly protease inhibitors
86
Stage 4 AIDS - what are empirical treatments for diarrhoeal disease?
Cryptosporidia - nitazoxanide/ paromomycin Cyclospora - co-trimoxazole Isospora belli – co-trimoxazole Microsporidia – albendazole Starting ART is treatment for all diarrhoeal disease
87
What are general side effects of NRTIs?
In general - | anaemia, lipodystrophy, lactic acidosis, liver cirrhosis/ hepatitis, pancreatitis, peripheral neuropathy
88
What are side effects of these NRTIs? Lamivudine Stavudine Tenofovir Zidovudine
Lamivudine - well tolerated Stavudine - no longer used as multiple side effects Tenofovir - renal disease, osteoporosis Zidovudine - anaemia, lipodystrophy, lactic acidosis, liver cirrhosis/ hepatitis, pancreatitis, peripheral neuropathy
89
What are general side effects of NNRTI?
``` Nausea Diarrhoea Hepatotoxicity Fever Rash ```
90
What are side effects of these NNRTIs? Efavirenz Nevirapine
Efavirenz (EFV) – psychiatric symptoms Nevirapine (NVP) – rash – SJS/ TEN (CD4 >250 count puts more at risk)
91
What are side effects of protease inhibitors?
diarrhoea diabetes lipodystrophy hepatitis
92
After starting ART, what other drugs should be commenced?
IPT - isoniazid preventative therapy 6 months, if no active TB Co-trimoxazole - until CD4 count improved
93
2x NRTI combinations - what drugs are in these combinations? Combivir Kivexa Truvada
Combivir - zidovudine/ lamivudine Kivexa - abacavir/ lamivudine Truvada - tenofovir/ emtricitabine
94
2x NRTI and 1x NNRTI come as combination drugs. What drugs are in these combinations? Trioday Viraday
Trioday - tenofovir/ lamivudine/ efavirenz Viraday - tenofovir/ emtricitabine/ efavirenz
95
If on NRTIx2/ NNRTI, and have virological failure, what steps would you take?
Change one of the NRTI Switch NNRTI to PI
96
Why does HIV resistance emerge?
Replicates 1 billion times/day. Reverse transcription is error prone. Selective pressure – rapid emergence of resistance Can be infected with resistant strain, but usually resistant virus is not as "fit" as wild virus
97
Which ART drugs are at high risk of having resistance emerge?
NRTI - emtricitabine/ lamivudine/ tenofovir/ zidovudine NNRTI - efavirenz/ nevirapine
98
Which ART drugs do not show much resistance?
Protease inhibitors
99
How does HIV evade immune system?
Hide - in sanctuary sites (Brain/ testes) Run - high levels virus turnover, high mutation rate
100
What is pathogenesis of IRIS in TB for example?
Low CD4 count - macrophages contain TB, but cannot be fully activated CD4 count increases due to ART IFN-gamma and other cytokines stimulate macrophages Macrophages produce overwhelming cytokine response - TNFalpha, IFNgamma, IL6 Excessive inflammation causes tissue destruction
101
HIV most important risk factor for reactivation of TB. New diagnosis HIV, how should you screen patient?
1. Check for active symptoms - then CXR if suspicious of active pulmonary TB 2. If no symptoms symptoms - IGRA. IGRA positive - CXR check for active TB IGRA negative - give patient 6 months isoniazid prophylaxis Active - give RIPE Latent - 6 months isoniazid prophylaxis
102
Why are sputum samples less reliable in advanced HIV? Why is IGRA less reliable in advanced HIV?
Reduction in smear positive cases, as no immune response/ cavitation. Use Genexpert HIV may give false negative IGRA test as cannot produce antibodies
103
Rifampicin is potent enzyme inducer, used in TB treatment How does this affect ART? - No interaction between rifampicin and NRTI - NNRTI
Efavirenz (nNRTI) – levels only reduced slightly, does not need dose adjustment Nevirapine (nNRTI) – rifampicin reduces levels greatly. Give higher dose of nevirapine – but risk of hepatotoxicity. Only use if have to - LMIC
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Rifampicin is potent enzyme inducer, used in TB treatment How does this affect ART? - PI - Integrase inhibitor
Lopinavir/ atazanavir (protease inhibitor) – reduces levels greatly. Severe hepatotoxicity, can only give ritonavir. Switch rifampicin to rifabutin (if need to be on protease inhibitor) Raltegravir/ dolutegravir (integrase inhibitor) – reduces levels greatly. Double the dose
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What are the 5Cs of HIV testing?
``` consent confidentiality counselling correct results connection to services ```
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Neurological disease can occur in HIV due to infections. What are other causes of non-infectious neurological disease?
Stroke - 5x more likely in HIV HIV associated neurocognitive disorder (HAND) – neuronal damage due to CNS inflammation (IRIS/ ARVs/ HIV replication CNS), direct neurotoxic effect of HIV
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What drug is used for pre-exposure prophylaxis? When is is taken?
Truvada - tenofovir/ emtricitabine Descovy - tenofovir/ emtrictabine 70-99% effective Every day dosing or Event based dosing (EBD) take 2 pills 2 – 24 hours before sex take 1 pill 24 hours later take 1 more pill 24 hours after that or Holiday PrEP 7 days daily dosing before the period 7 days daily dosing during the period (or for as long as the specific period lasts) 7 days daily dosing after the period.
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What are downsides to pre-exposure prophylaxis?
Increased risky sexual behaviour Does not protect from other STIs Need HIV test before treatment, and every 3 months
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What drugs are included in post-exposure prophylaxis? Must take within 72 hours Course lasts 28 days Re-test for HIV at 3 months
Truvada + Raltegravir
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Vertical transmission - approx 30% transmission risk in pregnancy, 20% transmission risk breast feeding What are risk factors for increasing transmission?
High viral load Maternal malnutrition Placental infection STI Premature birth Low birth weight Longer breast feeding Breast abscess/ mastitis
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How are these ART drugs affected in pregnancy? NRTI NNRTI Integrases Protease inhibitors
NRTIs/ NNRTIs - dose normal in pregnancy Pregancny - on antacids/ iron replacement - integrases don’t work as bind to metals. Normal dose in pregnancy Protease inhibitors effect reduced in pregnancy
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Why do HIV infected children progress rapidly to AIDS?
Immature T cells, so cannot suppress viral load
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How do HIV infected children present?
Malnutrition/ stunted growth Oral thrush Severe infection - pneumonia
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Which vaccines to avoid in HIV? Vacccines are less effective in HIV due to weakned immune response
``` BCG Measles/ Mumps/ Rubella Rotavirus Typhoid Varicella Yellow fever ``` Any live attenuated vaccine

Medical Microbiology and Virology (60 decks)

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