HIV Flashcards
How many distinct HIV viruses are there?
Two:
- HIV-1
- HIV-2
What is the most predominant type of HIV virus?
HIV-1
What type of virus is the HIV virus?
Retrovirus
How many RNA chains does the HIV virus have?
Two single chains of RNA
Describe the life-cycle of the HIV virus
- Binding: virus binds to host CD4 receptor molecules via the envelope glycoprotein gp 120 and co-receptors CCR5 and CXCR4.
- Fusion: subsequent conformational change results in the fusion between gp41 and the cell membrane.
- Reverse transcription: entry of the viral capsid followed by uncoating of RNA. DNA copies are made from both RNA templates. DNA polymerase from the host cell leads to formation of dsDNA.
- Integration: virally encoded DNA is inserted into the host genome - Integrase
- Transcription: regulatory proteins control transcription (an RNA molecule is now synthesized from the DNA template).
- Budding: the virus is reassembled (protease - needed for mature virus progeny) in the cytoplasm and budded out from the host cell
What are the 4 distinct strains of HIV?
- Group M - 98% of infections worldwide
- Group N
- Group O
- Group P
Describe the pathogenesis of HIV
- Virus transported by dendritic cells from mucosal surfaces
- GP120 reacts with CD4 and CCR5/CXCR4 -> entry into CD4 T cells, monocytes, macrophages and neural cells
- CD4 +ve cells migrate to lymphoid tissue
- Viral contents becomes integrated into nucleus of cell -> reverse transcription can take place
- As infection progresses - CD4 depletion/impaired function
What is the general progression of infection in HIV?
How can HIV be transmitted?
All fluids
- Sexual intercourse - Semen, cervical secretions
- Mother-to-child
- Contaminated blood, blood products, organ donation
- Contaminated needles (IVDU, Injections, Needle-stick injuries)
Where is HIV-2 most commonly found?
Most parts of WEst Africa
What enzyme integrates viral RNA into host DNA?
Viral integrase
What viral enzymes cleave initial viral proteins into enzymes and building blocks of the virus?
Viral proteases
What is seroconversion?
The time period during which a specific antibody develops and becomes detectable in the blood. After seroconversion has occurred, the disease can be detected in blood tests for the antibody
How soon after initial exposure does seroconversion occur?
2-6 weeks
What are features of HIV seroconversion?
Presents with flu-like syndrome:
- Fever
- Malaise
- Myalgia
- Pharyngitis
- Maculopapular rash
- Lymphdenopathy
- Mucosal ulceration
- Headache/asceptic meningitis - rare
What cells are susceptible to HIV infection?
- CD4+ T cells
- Macrophages
- Monocytes
- Neurons
What follows seroconversion?
Asymptomatic infection, or persistent generalised lymphadenopathy
How long can asymptomatic infection last for following seroconversion?
Can last for years
What proportion of individuals develop persistent generalised lymphadenopathy?
30%
What is persistent generalised lymphadenopathy?
Lymph nodes >1cm in diameter at >/= 2 extra-inguinal sites, persisting for > 3 months
What defines the first clinical stage of HIV infection?
Asymptomatic infection or PGL
What features define clinical stage II of HIV infection?
- Weight loss < 10%
- Minor cutaneous manifestations
- Herpes zoster in last 5 years
- Recurrent URTI
- Performance scale 1 - normal activity
What features define clinical stage III HIV infection?
- Weight loss > 10%
- Unexplained chronic diarrhoea > 1 month
- Unexplained prolonged fever > 1 month
- Oral candidiasis
- Oral hairy leukoplakia
- Pulmonary TB within past year
- Several bacterial infections
- Performace scale 3 - bedridden <50% of day
What features suggest clinical stage IV HIV infection (AIDS defining illnesses)?
- HIV wasting synrome
- PCP
- Toxoplasmosis of the brain
- Cryptosporidiosis with diarrhoea > 1 month
- CMV of organ other than liver, spleen or lymph nodes
- HSV > 1 month
- Progressive multifocal leukoencephalopathy
- Any disseminated endemic mycosis
- Candidiasis of oesophagus/trachea/bronchi/lung
- Atypical disseminated TB
- Extrapulmonary TB
- Kapose’s sarcoma
- HIV encephalopathy
- Performace scale 4 - bedridden > 50% day in last month
What respiratory conditions are regarded as AIDS defining illnesses?
- TB
- Pneumocystis
What neurological conditions are regareded as AIDS defining illnesses?
- Cerebral toxoplasmosis
- Primary cerebral lymphoma
- Cryptococcal meningitis
- Progressive multifocal leucoencephalopathy
What neurological conditions would you consider doing HIV testing in?
AIDS defining illnesses, plus:
- Aseptic meningitis/encephalitis
- Cerebral abscess
- SOL of unknown cause
- Guillain-Barre syndrome
- Transverse myelitis
- Unexplained Peripheral neuropathy
- Lecuoencephalopathy
What dermatological conditions are regarded as AIDS defining illnesses?
Kaposi’s sarcoma
What dermatological conditions would you consider doing HIV testing in?
- Kaposi’s Sarcoma
- Severe/intractable seborrhoeic dermatitis
- Severe/reclacitrant psoriasis
- Recurrent/multidermatomal HSV
What GI disorders are regarded as AIDs defining illnesses?
Persistent cryptosporidiosis
What GI conditions would you consider offering an HIV test in?
- Persistent cryptosporidiosis
- Oral candidiasis
- Oral hairy leukoplacia
- Chronic diarrhoea of unknown cause
- Weight loss of unknown cause
What oncological problems are regarded as AIDs defining illnesses?
Non-Hodgkin’s Lymphoma
What is Kaposi’s Sarcoma?
A cancer that causes patches of abnormal tissue to grow under the skin, in the lining of the mouth, nose, and throat, in lymph nodes, or in other organs
How does cerebral toxoplasmosis present?
- Confusion
- Seizures
- Fever
- Headache
- Drowsiness/Coma
- Signs of braainstem/spinal cord problems
What is the following?
Oral hairy leucoplakia - a white patch on the side of the tongue with a corrugated or hairy appearance.
What is progressive multifocal leukoencephalopathy?
A rare and usually fatal viral disease characterized by progressive damage (-pathy) or inflammation of the white matter (leuko-) of the brain (-encephalo-) at multiple locations (multifocal).
What virus is responsible for progressive multifocal leukoencephalopathy?
JC virus
What is the following?
Oral candidiasis
What eye disease is regarded as an AIDs defining illness?
CMV retinitis
What is the definition of AIDS?
HIV + AIDs defining illness
What CD4 count will someone with AIDs usually have?
<200x106/L
What are the main signs which suggest that HIV is progressing?
- Chronic fever
- PGL
- Cough > 1 month
- Chronic diarrhoea
- Oral thrush
- 10% weight loss in last month
- TB/HZ
If you suspected HIV, what investigations would you consider doing?
- Bedside - Rapid HIV serum test (finger prick), Mantoux test
- Bloods - FBC, U+E’s, LFTs, Hep B/C, Toxoplasma serology, Pregnancy test
- HIV specific - 4th Gen. ELISA for HIV Ab + Ag (p24 antigen)
- Imaging - CXR
What is important to remember when trying to determine if someone has HIV with regards to test results?
Remember the diagnostic window - time during which diagnostic markers are not detectable
When are serum IgG and IgM levels detectable for HIV?
After 3 months, then fall after AIDs develops
What is P24 antigen?
p24 protein is present during high viral replication and so is detectable in the blood during acute infection (first 3 months) and again during late stages of infection (AIDS). Its use, therefore, is as a supplementary test during the window period
What might you find on CXR in someone with HIV?
- Pneumocystis jirovecii pneumonia
- TB
If someone was tested for HIV and came back as being antigen/antibody negative, would this confirm that they were not infected with HIV?
No - have to retest tro make sure diagnosis has not been missed
What should HIV patients be monitored for regularly?
TB infection
What investigations would you do to monitor HIV?
- Clinical assessment
- Viral RNA load
- CD4 count
- HIV resistance testing
- Other bloods - FBC, U+Es, LFT, lipid profile, glucose
How often would you monitor CD4 levels?
3-6 months
What is viral load used for?
Determine effectiveness of antiviral therapy
What infections should all newly diagnosed HIV patients be screened for?
- TB
- Toxoplasma
- CMV
- Hepatitis B + C
- Syphilis
When is viral load highest?
Initially high during acute infection, then falls to low levels, then rises again in later stages of the disease (6-8 years after infection)
How is viral load measured?
Viral PCR quantitation
What is the normal CD4 level?
500-1500
At what CD4 level would you consider starting someone on antiretrovirals?
<350
What are indications for starting antiviral therapy in HIV?
- CD4 < 350
- AIDS defining illness
- Pregnant women
- HIV-associated nephropathy
- Co-infection with HBV
What are the main types of anti-retroviral drugs used in HIV?
- Nucleoside recerse transcriptase inhibitors
- Non-nucleoside reverse transcriptase inhibitors
- Protease inhibitors
- CCR5 antagonists
- Integrase strand transfer inhibitors
- Pharmakokinetic enhancers/boosters
What is the reason for someone to have persistent generalised lymphadenopathy?
Due to follicular hyperplasia caused by HIV infection
How much does 4th generation HIV testing reduce the window period to (in terms of number of days that a false negative can occur in)?
Approximately 10 days
What are examples of Rapid point-of-care testing for HIV?
- Finger-prick
- Mouth swab
What is viral load used for?
- Quantification of HIV RNA
- Monitoring of ART efficacy
Is rapid testing confirmatory of HIV?
No - needs serological confirmation with 4th Gen ELISA
What is viral/nucleic acid PCR used for?
Used to test for presence of virus
What are features of PCP infection in HIV?
- Progressive SOB on exertion
- Malaise
- Dry cough
- Tachypnoea
What might the following be in someone with SOB and dry cough with HIV?
PCP - perihilar infiltrates is classic sign
What are features of cryptococcal meningitis in someone with HIV?
- Meningism - headache, fever, neck stiffness
- Molloscum-like skin lesions
- Lung disease
How can CMV infection present in HIV?
- Retinitis
- Encephalitis
- GI disease
- Hepatitis
- Bone marrow suppression
- Pneumonia
What would be your differential diagnosis for a fever in an HIV patient?
- Intraoral abscess
- Sinusitis
- Pneumonia
- TB
- Endocarditis
- Meningitis
- Encphalitis
- Pyomyositits
- Lymphoma
- Any non-HIV cause
What would be your differential for lyphadenopathy in HIV patients?
- PGL
- TB
- Syphillis
- Histoplasmosis
- Cryptococcus
- Lymphoma
- Kaposi’s Sarcoma
- Local infection
What would be your differential diagnosis for a rash in someone with HIV?
- Drug reaction
- Herpes zoster
- Scabies
- Cutaneous cryptococcus
- Kaposi’s Sarcoma
- Seborrhoeic dermatitis
What would be your differential diagnosis for someone presenting with a cough/SOB in someone with HIV?
- CAP
- PCP
- TB
- Bronchial compression - lymphoma, TB, kaposi’s
- Pulmonary Kaposi’s sarcoma
- Cardiac failure - HIV cardiomyopathy, pericardial effusion, HIV vasculopathy
What would be your differential diagnosis for someone with diarrhoea who had HIV?
- Slamonella
- Shigella
- C. diff
- Amoebiasis
- Giardia
- Cryptosporidia
- CMV
- HIV enteropathy - diagnosis of exclusion
What might cause abdominal pain in those with HIB?
- TB
- CMV colitis
- Pancreatitis
- Pregnancy
What could cause headaches/seizures/focal neurology in HIV patients?
- Meningitis - bacterial, TC, syphillis
- Empyema
- SOL - toxo, lymphoma, TBoma
- Adverse drug reaction
- HIV encephalopathy
- Progressive multifocal leukoencephalopathy
- Stroke
What could cause dysphagia in someone with HIV?
- Candidiasis
- HSV
What might cause eye disease in HIV?
- CMV
- Herpes zoster
What might cause deranged LFTs in HIV?
- Viral hepatitis
- Drug-induced liver injury
- HIV cholangiopathy
- Lymphoma
- CCF
How do nucleoside/nucleotide reverse transcriptase inhibitors work?
Inhibit reverse transcriptase and the conversion of viral RNA into DNA
How do CCR5 antagonists work?
Inhibit entry of the virus into the cell by blocking the CCR5 receptor
How do integrase strand transfer inhibitors work?
Inhibit integrase and prevent HIV DNA integrating into the nucleus
How do protease inhibitors work?
Inhibit protease, an enzyme ivolved in the maturation of virus particles
What is the main purpose of pharmacokinetic enhancers/boosters?
Increase the effectiveness of antiretroviral drugs allowing lower doses
What would you consider for treatment-naive individuals in HIV?
2 NRTIs, plus one of:
- Boosted protease inhibitor
- NNRTI
- Integrase inhibitor
What are examples of NRTIs?
- Zidovudine (AZT)
- Didanosine (ddI)
- Zalcitabine (ddC)
- Lamivudine (3TC)
- Stavudine (d4T)
- Abacavir
What are side effects of NRTI’s?
- Marrow toxicity
- Neuropathy
- Lipodystrophy
- GI disturbance
- Anorexia
- Pancreatitis
- Hepatic dysfunction
- Lactic acidosis
What are the adverse reactions associated with protease inhibitors?
- Hyperglycaemia
- Lipodystrophy
- Diarrhoea
- Insulin resistance
- Dyslipidaemia
- Jaundice
- Hepatitis
What are adverse reactions of NNRTIs?
- Nausea and vomiting, abdominal pain and diarrhoea common
- Hypersenstivity reaction
- Rash (can be severe)
- CNS / psychiatric disturbance
- Hepatotoxicity
What are side effects of integrase inhibitors?
- Rash
- GI disturbance
- Insomnia
Why is adherence incredibly important in HIV treatment?
Deccreased adherence causes increased resistance due to error prone replication process of virus
What baseline tests should you consider doing in somone you are about to start on ART treatment for HIV?
- CD4
- Viral load
- FBC
- LFT
- U+E’s
- Pregnancy Test
- Viral genotyping for resistance
What measures would you take for managing a pregnant woman with HIV who are having a vaginal delivery?
- Continue HAART through labour
- Avoid foetal blood sampling
- Avoid amniotomy
- Use oxytocin for augmentation
- Avoid rotational/mid-cavity forceps
When should C-section be offered to women with HIV?
38 weeks gestation if:
- AZT monotherapy
- Viral load > 50 copies/mL
- Co-infected with hepatitis C
What post-partum measures should be taken in a mother with HIV?
- Avoid breastfeeding - cabergoline to suppress lactation
- ART for newborn within 4hrs birth
- Test at 1wk, 6 wks, 12 wks and 18 months for HIV
- Dicuss contraception, annual smears with mother
What Post-exposure prophylaxis is used for HIV?
3 drugs, for 28 days, within 72hrs of high-risk event. The drugs given are anti-retrovirals, anti-diarrhoeals and anti-nausea medications.
How long does it take for HIV infection to become established?
48-72 hours
What medications would you give someone with a CD4 count >500?
None - Monitored but not given HAART
What is HAART?
Highly active Anti-retroviral therapy
The use of multiple drugs that act on different viral targets. Usually consists of 2 NRTIs and a protease inhibitor, NNRT or integrase inhibitor
What investigations would you consider doing to diagnose HIV?
- 4th Gen. Elisa - Combined HIV antibody and p24 antigen tests
- Point-of-care tests - finger-prick or mouth swabs are used in some genito-urinary medicine (GUM) clinics, and results can be available within 1 hour. If the result is positive, a laboratory test should be done, as point-of-care tests are more likely to have false-positive results.
