Case 6 HIV/Hep B/C Flashcards
What is HIV virus structure?
- HIV is a single stranded, positive sense, enveloped RNA retroviridae family
- Need reverse transcriptase to transcribe a complementary double-stranded pro-viral DNA (ssRNA dsDNA)
- Pro-viral DNA enters host cell nucleus and integrate itself into host DNA
- Every time when immune cells are activated due to infection, new HIV viruses are being transcribed and translated bud off cell membrane to infect more cells
What is the target cells for HIV virus?
Target CD4+ cells (cells that have CD4 molecules)
- Macrophages, T helper cells, dendritic cells
- HIV attach to CD4 molecule via its gp120 protein found on its envelope
- HIV also attaches to co-receptor via its gp120 protein
o CXCR4 on T cells
o CCR5 on macrophages, T helper cells, dendritic cells
- Genetic mutation of co-receptors or fewer on cell surface disease resistance, slower disease progression
What is window period for HIV?
Up to 6-12 weeks, where HIV testing can be inaccurate
How is HIV transmitted?
Sexual intercourse, IVDU sharing needles, mother-child (placenta, delivery, breast milk)
- PRESENT IN blood, genital fluids, breast milk
- NOT PRESENT in saliva, sweat, urine or faeces
What are the different phases of HIV?
- Acute infection: R5 strain binds to CCR5 receptors on macrophages, dendritic cells and T cells
Patient typically experience flu-like symptoms BUT INFECTIOUS, hard to detect on tests - Dendritic cells which normally stays in the epithelial or mucosal tissues migrate to lymph nodes
- Infect more immune cells in lymph nodes, leading to a big increase in HIV replication and amount of virus found in patient’s blood
WINDOW PERIOD: UP TO 12 WEEKS - Immune system is triggered to control viral replication –> lower level of HIV virus but still detectable by 12 weeks –> enter chronic phase
- Chronic/clinically latent phase (2-10 years)
Virus slowly increases and T cells slowly decreases
T cells remain 500 cell/mm3: still can fight infections except TB
Some patients develop X4 strain of HIV which targets CXCR4 coreceptors: only T cells and destroy 90% of T cell in lymph nodes - Symptomatic phase: 200-500 T cells/mm3
o Swollen lymph nodes
o Leucoplakia on tongue caused by Epstein Barr
o Oral candidiasis yeast infection - AIDS: < 200 T cells/mm3
Persistent fever, fatigue, weight loss, diarrhoea
What is AIDS and what are some aids defining conditions?
- AIDS: < 200 T cells/mm3
Persistent fever, fatigue, weight loss, diarrhoea
AIDS defining
o Recurrent bacterial pneumonia
o Pneumocystis pneumonia Chest X ray: hazy looking areas
o Histoplasmosis fever, fatigue, weight loss, cough, dyspnoea
o Fungal infections (candidiasis of oesophagus)
o Tumours (kaposi sarcoma)
o Primary lymphoma
o CNS toxoplasmosis encephalitis
o HIV-associated dementia altered mental state, cerebral atrophy
What are some symptoms and signs of HIV?
Symptoms
- Fever/night sweats/lethargy/malaise/weight loss/nausea/vomiting
- Lymphadenopathy, rash, oral thrash
Examinations
- Generalised lymphadenopathy, noting size, site, mobility and tenderness
- Skin infection: HIV-associated rashes, fungal infections, Kaposi sarcoma (purple patches/nodules)
- Mouth: oral thrush, leucoplakia
- Chest and CVS exam: infections
- GI exam: hepatosplenomegaly
- Genitalia exam
- Neuro exam
What are some investigations to diagnose HIV?
4th generation antibody/antigen test
- Detect antibodies against HIV (IgM and IgG), p24 antigen
- Can detect HIV-1 and HIV-2, WINDOW PERIOD might be inaccurate
HIV antibody enzyme immunoassay
- Takes up to 3 weeks to become positive after the onset of clinical signs
- Also can do a differentiation immunoassay either or both
P24 antigen test
- Become positive within a few days of symptoms and be absent after two weeks
Nucleic acid test (RNA/DNA)
- Most sensitive test for HIV
infection in newborns
HIV RNA viral load by Reverse transcriptase PCR
- Measures active replication of HIV in blood
- Not recommended to diagnose acute HIV infection due to false-positive rate indicated by low viral levels
CD4 count
- Indicates health of host’s immune system
- Average CD4 count for HIV-negative adult 800 cells
- < 500 cells asymptomatic but inc risks of general infections
- < 350 cells substantial immune suppression
- < 200 cells AIDS
HIV genotype
Drug resistance testing
To determine if the disease has progressed to AIDS
- T cells count < 200 cell/mm3
- Assess for presence of AIDS-defining conditions
- HIV viral load tests
Co-morbid tests
- Basic bloods (CBE, LFT, EUC, cholesterol, BGL)
- Hep A, B and C serology
- Serology: Syphilis, toxoplasma, cytomegalovirus
- Chlamydia and gonorrhoea at exposed site (vaginal, urethral, throat and rectal)
What is behavioural management for HIV?
Risk reduction counselling - Reduce further transmission of HIV - Safe sex education (use condoms) ART counselling - Preparing patient to commit to long-term ART Good nutrition - Healthy balanced diet - No alcohol - Multi-vitamin
3 monthly tests - CBE EUC, LFT 6 monthly tests - Liver and renal function - Viral load, CD4 count - STI screening (Hep A, B, syphilis, if not immune give vaccinations) Antiretroviral treatment side effect - Bone mineral density (2-4 years) Mental health, referrals Vaccinations - Can give non-live vaccinations (flu, meningococcal, pneumococcal, Hep A) CVS disease (6-12 monthly) most patients died from - BP, weight, BGL, alcohol, smoking
What is anti-retroviral treatment?
2 NRTIs + 1 integrase inhibitors
Goal: <40 copies/mL, viral load dec 10-fold within 4-8 weeks, restore immunological function
Undetectable = Untransmittable
Nucleoside reverse transcriptase inhibitors (NRTI)
Mechanisms: Competitively inhibit reverse transcriptase and viral DNA synthesis
Side effects: Lactic acidosis (secondary to mitochondrial toxicity)
Rash, bone marrow suppression
Non-Nucleoside reverse transcriptase inhibitors (NNRTI)
Mechanisms: Non-competitively inhibit function of reverse transcriptase
Side effects: Vivid dreams/nightmares, agitation
Integrase Strand Transfer Inhibitors (INST)
Mechanisms: Inhibit HIV integrase, stopping insertion of viral DNA into host DNA
Side effects: Elevated serum creatinine, myopathy, worsening anxiety/depression/agitation
Protease Inhibitors (PI) Mechanisms: Inhibit HIV integrase, stopping insertion of viral DNA into host DNA
What are some differences between HAV, HBV and HCV?
Transmission
HAV: faecal oral
HBV: body fluids
HCV: blood
Chronic
HAV: no
HBV: yes
HCV: yes
vaccination
HAV: yes
HBV: yes
HCV: no
What are some risk factors of HCV?
Risk factors
- IV drug user HIGH RISK
- Tattoos or body piercings medium risk
- Vertical transmission low risk
- needle stick injury low risk
- Sex workers
- ATSI
- Liver disease
What are some symptoms and signs of HCV?
Acute viral hepatitis presentation - Flu-like symptoms: fatigue, headache, anorexia, nausea/vomiting, low grade fever - Jaundice, joint pain/stiffness Usually after 1-2 weeks - Jaundice - Pale stools - Dark urine - RUQ pain
Signs
- Generally unwell
- Overt jaundice, jaundice of sclera
- RUP tenderness
- Hepatosplenomegaly
- Ascites
- Lymphadenopathy
What are some investigations of HCV?
LFT
- Inc ALT, AST but ALT>AST
- Inc conjugated (leaks out when bile ducts are damaged) and unconjugated bilirubin (apoptosis of hepatocytes lose the ability to conjugate bilirubin)
Urinalysis
- Inc urobilinogen
CBE: WCC, platelet
HCV antibody against core protein and non-structural proteins
- Negative antibody does not rule out acute HCV infection or in severely immunocompromised patients should be repeated in 3 months
- Positive result indicates exposure to HCV
Nucleic acid amplification tests (NAAT)
- Include PCR for HCV RNA, DNA analysis
- absence of HCV RNA can mean patient has cleared virus after acute exposure
Viral genotyping (HCV 1-6)
- should be done to assist in determining dose and duration of therapy
How does investigations result indicate HCV?
Test outcome Interpretation
HCV antibody non-reactive –> Negative for HCV
HCV antibody reactive –> Positive for HCV
HCV antibody reactive, HCV RNA detected –> Positive for active HCV
HCV antibody reactive, HCV RNA not detected –> Past HCV, not active infection
