HIV

Question 1

Kaposis sarcoma

Answer 1

Caused by HHV-8 infection in HIV positive individuals AIDS defining illness. Multiple purplish nodules in the skin

Question 2

CD4 count 200 - 500 cells/mm³

Answer 2

• Oral thrush –> Secondary to Candida albicans
• Shingles -> Secondary to herpes zoster
• Hairy leukoplakia -> Secondary to EBV
• Kaposi sarcoma -> Secondary to HHV-8

Question 3

CD4 count 100 - 200 cells/mm³

Answer 3

• Cryptosporidiosis
• Cerebral toxoplasmosis
• Progressive multifocal leukoencephalopathy -> Secondary to the JC virus
• PJP
• HIV dementia

Question 4

CD4 count 50 - 100 cells/mm³

Answer 4

• Aspergillosis -> Secondary to A.fumigatus
• Oesophageal candidiasis ->Secondary to Candida albicans
• Cryptococcal meningitis
• Primary CNS lymphoma ->Secondary to EBV

Question 5

CD4 count < 50 cells/mm³

Answer 5

• Cytomegalovirus retinitis -> Affects around 30-40% of patients with CD4 < 50 cells/mm³
• Mycobacterium avium-intracellulare infection

Question 6

HIV, neuro symptoms, widespread demyelination

Answer 6

Progressive multifocal leukoencephalopathy. Caused from JC virus:

• widespread demyelination due to infection of oligodendrocytes by JC virus (a polyoma DNA virus)
• Symptoms, subacute onset -> behavioural changes, speech, motor, visual impairment
• CT: single or multiple lesions, no mass effect, don’t usually enhance.
• MRI is better - high-signal demyelinating white matter lesions are seen

Question 7

HIV: neurocomplications

Answer 7

Focal neurological lesions:

• Toxoplasmosis - 50% of cerebral lesions
• Primary CNS lymphoma - 30% of cerebral lesions assoc with EBV
• TB - much less common than above. single enhancing lesion on CT

Generalised neurological disease:

• encephalitis
• cryptococcus
• progressive multifocal leukoencephalopathy - AIDS dementia complex

Question 8

Toxoplasmosis

Answer 8

• accounts for around 50% of cerebral lesions in patients with HIV.
• CT: MULTIPLE lesions with ring or nodular enhancement.
• SPECT negative Constitutional symptoms, headache, confusion + drowsiness.
• management: sulfadiazine and pyrimethamine

Question 9

Primary CNS lymphoma

Answer 9

• Assoc with EBV
• CT: SINGLE lesion (or multiple) homogenous aka solid enhancing lesions.
• Thallium SPECT positive treatment generally involves steroids (may significantly reduce tumour size), chemotherapy +/- whole brain irradiation.
• Surgical may be considered for lower grade tumours

Question 10

HIV drugs rule of thumb

Answer 10

• NRTIs end in ‘ine’
• Pis: end in ‘vir’
• NNRTIs: nevirapine, efavirenz

Question 11

Highly active anti-retroviral therapy (HAART)

Answer 11

At least 3 drugs - typically 2 NRTI and either a PI or a NNRTI

Question 12

Entry inhibitors

Answer 12

• maraviroc (binds to CCR5, preventing an interaction with gp41),
• enfuvirtide (binds to gp41, also known as a ‘fusion inhibitor’) prevent HIV-1 from entering and infecting immune cells

Question 13

Nucleoside analogue reverse transcriptase inhibitors (NRTI)

Answer 13

• examples: zidovudine (AZT), abacavir, emtricitabine, didanosine, lamivudine, stavudine, zalcitabine, tenofovir
• general NRTI side-effects:
  
  • peripheral neuropathy
• tenofovir: used in BHIVAs two recommended regime NRTI. Adverse effects include renal impairment and ostesoporosis
• zidovudine: anaemia, myopathy, black nails
• didanosine: pancreatitis

Question 14

Non-nucleoside reverse transcriptase inhibitors (NNRTI)

Answer 14

• examples: nevirapine, efavirenz
• side-effects: P450 enzyme interaction (nevirapine induces), rashes

Question 15

Protease inhibitors (PI)

Answer 15

• examples: indinavir, nelfinavir, ritonavir, saquinavir
• side-effects: diabetes, hyperlipidaemia, buffalo hump, central obesity, P450 enzyme inhibition
• indinavir: renal stones, asymptomatic hyperbilirubinaemia
• ritonavir: a potent inhibitor of the P450 system

Question 16

Integrase inhibitors

Answer 16

• raltegravir, elvitegravir, dolutegravir

Question 17

Immune reconstitution inflammatory syndrome

Answer 17

• can occur in HIV positive patients when starting anti-retrovirals; this is an immune phenomenon that results in the clinical worsening of a pre-exisiting opportunistic infection.
• TB is the most common cause of IRIS

Question 18

HIV seroconversion

Answer 18

• HIV seroconversion is symptomatic in 60-80% of patients and typically presents as a glandular fever type illness.
• Increased symptomatic severity is associated with poorer long term prognosis. It typically occurs 3-12 weeks after infection.
• Features: sore throat, lymphadenopathy malaise, myalgia, arthralgia, diarrhoea maculopapular rash mouth ulcers, rarely meningoencephalitis
• Dx: antibodies to HIV may not be present HIV PCR and p24 antigen tests can confirm diagnosis

Question 19

Pregnancy

Answer 19

Factors which reduce vertical transmission (from 25-30% to 2%)

• maternal antiretroviral therapy
• mode of delivery (caesarean section)
• neonatal antiretroviral therapy
• infant feeding (bottle feeding)

Antiretroviral therapy

• all pregnant women should be offered antiretroviral therapy regardless of whether they were taking it previously

Mode of delivery

• vaginal delivery is recommended if viral load is less than 50 copies/ml at 36 weeks, otherwise caesarian section is recommended a zidovudine infusion should be started four hours before beginning the caesarean section
• Neonatal antiretroviral therapy zidovudine is usually administered orally to the neonate if maternal viral load is <50 copies/ml. Otherwise triple ART should be used. Therapy should be continued for 4-6 weeks. Infant feeding in the UK all women should be advised not to breast feed

Question 20

Pneumocystis jiroveci

Answer 20

• unicellular eukaryote, generally classified as a fungus but some authorities consider it a protozoa
• PCP is the most common opportunistic infection in AIDS
• all patients with a CD4 count < 200/mm³ should receive PCP prophylaxis
• Extrapulmonary manifestations are rare (1-2% of cases), may cause hepatosplenomegaly lymphadenopathy choroid lesions
• Ix:
  
  • CXR: typically shows bilateral interstitial pulmonary infiltrates but can present with other x-ray findings e.g. lobar consolidation. May be normal exercise-induced desaturation sputum often fails to show PCP,
  • BAL often needed to demonstrate PCP (silver stain shows characteristic cysts)
• Mx:
  
  • co-trimoxazole IV pentamidine in severe cases aerosolized pentamidine is an alternative treatment for Pneumocystis jiroveci pneumonia but is less effective with a risk of pneumothorax steroids if hypoxic (if pO2 < 9.3kPa then steroids reduce risk of respiratory failure by 50% and death by a third)

Question 21

Cancers associated with HIV

Answer 21

Question 22

Delta32 mutation in CCR5

Answer 22

Conveys resistance to HIV1 in homozygous patients

Question 23

Toxoplasma Encephalitis

Answer 23

Question 24

Side effects of HIV-PIs

Answer 24

• increased chlesterol and triglyceride concentrations, assoc with insulin resistance and DM
• Also assoc with an increased risk of MI
• hepatotoxicity and rash

Question 25

Side Effects of CCR5 antagonists

Answer 25

rash hepatotoxicity

Question 26

Fiebig Stages of HIV

Answer 26

Fiebig Stages I to VI I - Viral RNA PCR positive (first positive study)

Question 27

Side Effects of Fusion Inhibitors (Anti-retrovirals)

Answer 27

Question 28

Side Effects of NNRTIs

Answer 28

Question 29

PrEP for HIV regimen

Answer 29

**Tenofovir (disoproxil fumarate) and Emtricitabine** PBS streamline authority * Adult patients who are HIV negative * Who are high risk of contracting HIV * Before starting PrEP * Test for HIV * Check renal function **eGFR \> 60** * **Check for other STIs and give vaccines**