Human immunodeficiency virus (I) Flashcards
What is HIV?
Retrovirus that infects and replicates in human lymphocytes and macrophages, resulting in immunodeficiency
Where does HIV primarily replicate in?
Human CD4+ T cells and macrophages
What is HIV transmitted via? (4)
- sexual contact / fluids (majority of cases)
- heterosexual = most common mode of transmission
- homosexuals are at greater risk in the West
- before birth or during delivery
- during breastfeeding (breast milk)
- blood - sharing contaminated needles and syringes in IVDU / blood transfusions
How does HIV enter CD4+ lymphocytes?
Binding to their CD4 molecule + GP120 receptors
Describe the pathophysiology of HIV infection.
- enters CD4+ T cells by binding to CD4 molecule + gp120 receptors
- retrovirus = uses reverse transcriptase to transcribe complementary double-stranded piece of proviral DNA –> incorporation of HIV genetic material into host genome
- when immune cell is activated it inadvertently transcribes and translates new HIV virus which bud off from cell membrane to infect more cells
- –> dissemination of HIV, cell death and eventual CD4+ T cell depletion
What is HIV-1?
Responsible for global epidemic
What is HIV-2?
Less pathogenic, restricted mostly to West Africa
What is toxoplasmosis (HIV)?
Happens in 50% of cerebral lesions in HIV patients
What are the symptoms of toxoplasmosis (HIV)? (4)
- constitutional symptoms
- headache
- confusion
- drowsiness
What imaging do we do for toxoplasmosis (HIV)?
CT showing single or multiple ring-enhanced lesions
How do we manage toxoplasmosis (HIV)?
Pyrimethamine + sulphadiazine for 6 weeks
What are the stages of HIV infection?
- seroconversion - transition from infection with HIV to detectable presence of antibodies in blood - symptomatic (60-80%), presents 3-12 weeks after infection
- early/asymptomatic
- AIDS
What are the clinical features of HIV (stage 1 - seroconversion)? (8)
Glandular fever type illness:
- fever, night sweats, weight loss
- generalised lymphadenopathy
- sore throat
- malaise, myalgia, arthralgia
- diarrhoea
- maculopapular rash
- mouth ulcers
- rarely: meningoencephalitis
What are the clinical features of HIV (stage 2 - early/asymptomatic)? (3)
- apparently well
- persistent lymphadenopathy
- progressive minor Sx - rash, oral thrush, weight loss
What is stage 3 of HIV?
AIDS - syndrome secondary disease from immunodeficiency
What are some direct effects from HIV infection? (6)
- neurological - polyneuropathy (peripheral), dementia
- lung - lymphocytic interstitial pneumonitis
- heart - myocarditis, cardiomyopathy
- GI - anorexia, wasting
- eyes - cotton wool spots
What are some secondary effects from immunodeficiency in HIV? (5)
- bacterial infection - TB, skin infections, pneumococcal infections
- viral - CMV, HSV, VZV, HPV, EBV
- fungal - candidiasis, Pneumocystis jirovecii pneumonia, Cryptococcus, invasive aspergillosis
- protozoal - toxoplasmosis
- tumours - Kaposi sarcoma, SCC, Hodgkin’s/non-Hodgkin’s lymphoma (hepatomegaly/splenomegaly)
What are some risk factors for HIV infection? (6)
- HIV-infected blood transfusion
- IV drug use
- unprotected sexual intercourse (heterosexual and MSM)
- percutaneous needle stick injury
- West Africa residence (HIV-2)
- maternal HIV infection
What are the first-line investigations for HIV? (4)
- serum HIV enzyme-linked immunosorbent assay (ELISA)
- serum HIV rapid test
- HIV non-invasive tests
- serum Western blot
What is the standard first-line investigation for HIV infection?
Combination test - HIV p24 antigen and HIV antibody test
What do we do if combination test (HIV p24 antigen and HIV antibody) is positive for HIV?
Repeat to confirm diagnosis alongside starting treatment
What is the p24 antigen (HIV)?
Viral core protein that appears early in blood as viral RNA levels rise (earlier than antibodies) –> present 1 to 3/4 weeks after exposure
How can we detect HIV antibodies?
Serum HIV enzyme-linked immunosorbent assay (ELISA) - positive for HIV antibodies after 4-6 weeks (however these may not be present in early infection, p24 antigens present early)
How can we track immune status in HIV?
CD4+ count
What are some differential diagnoses for HIV? (7)
- infectious mononucleosis (fever, lymphadenopathy, pharyngitis, maculopapular rash, EBV +ve)
- CMV infection (fever, lymphadenopathy, rash, splenomegaly)
- influenza
- common cold
- viral hepatitis (RUQ pain, jaundice)
- secondary syphilis (maculopapular rash)
- COVID-19
What is the first-line management for HIV infection?
Antiretroviral therapy (combination of at least 3 drugs) ASAP:
2 NRTIs + 1 PI/NNRTI
NRTI = nucleotide reverse transcriptase inhibitor
PI = protease inhibitor
NNRT = non-nucleoside reverse transcriptase inhibitor
What NRTIs are there for HIV? (3)
2 required for antiretroviral therapy:
- Zidovudine
- Abacavir
- Tenofovir
What NNRTIs are there for HIV? (2)
1 NNRTI or PI required for antiretroviral therapy:
- Nevirapine
- Efavirenz
What PIs are there for HIV? (3)
1 NNRTI or PI required for antiretroviral therapy:
- Indinavir
- Nelfinavir
- Ritonavir
What are some side effects of antiretroviral therapy for HIV?
- NRTI - peripheral neuropathy, renal impairment
- NNRTI - P450 enzyme interaction, rashes
- PI - diabetes, hyperlipidaemia, buffalo hump, obesity, P450 inhibition, renal stones
What other drugs are there HIV antiretroviral therapy? (2)
- entry inhibitors - prevent HIV-1 from entering and infecting immune cells
- integrase inhibitors - block enzyme that inserts viral genome into host DNA
What supportive care do we provide for HIV? (5)
- counselling
- prophylaxis of opportunistic infections
- treating other infections
- comorbidity management
- vaccinations - pneumococcal, meningococcal, influenza, hepatitis B, HPV, tetanus/diphtheria/pertussis
How do we prevent HIV in high-risk individuals?
HIV Pre-Exposure Prophylaxis (PrEP) - Tenofovir (daily use to reduce transmission)
What do we give patients up to 72 hours after potential exposure to HIV?
HIV Post-Exposure Prophylaxis (PEP) which is a short course of antiretroviral therapy for 4 weeks
What do we give for HIV if CD4+ count <200mm3?
Co-trimoxazole as prophylaxis against Pneumocystis jirovecii pneumonia
How do we monitor HIV patients?
HIV RNA testing after ART initiation until levels below detection limits - 2,4,8 weeks then every 2 weeks
Once viral suppression achieved - repeat every 3-6 months
What are some complications of HIV? (5)
- acute seroconversion
- AIDS
- opportunistic infections - candidiasis, Pneumocystis jirovecii pneumonia, recurrent pneumonia, toxoplasmosis, HIV encephalopathy
- secondary malignancies
- neuropsychiatric disease
Describe the prognosis of HIV.
If untreated, leads to death on average 8-10 years after infection
If receiving adequate ART, no changes in life expectancy to healthy individuals
