HIV Flashcards
1
Q
Target cells for HIV infection:
A
- Dendritic cells
- Macrophages
- CD4+ T cells
2
Q
Modes of transmission HIV:
A
- Sexual transmission - highest in MSM in developed countries, heterosexual transmission common in Africa
- Parenteral transmission - IVDU largest group, also haemophiliacs and random blood transfusion recipients
- Mother to infant - transplacental in utero spread, during delivery, breastfeeding
- Healthcare workers - small but definite risk (0.3% risk if no ART given)
3
Q
Properties and structure of HIV:
A
- Retrovirus of lentivirus family
- HIV 1 →US, Europe, Central Africa
- HIV-2 → West Africa, India
-
Structure:
- Core containing:
- Capsid protein p24
- Nucleocapsid protein p7/p9
- 2 copies viral genomic RNA
- 3 viral enzymes → protease, reverse transcriptase, integrase
- Core surrounded by matrix protein p17
- Lipid envelope derived from host cell membrane
- gp 120 and gp 41 (glycoproteins) stud the envelope
- Core containing:
4
Q
Description of life cycle of HIV:
A
- HIV binds to CD4 molecule on target cells
- For entry into cell gp 120 also needs to bind to coreceptors
- CCR5 and CXCR4
- Different strains bind to different coreceptors - R5 strains select for CCR5 and preferentially infect macrophages (M-tropic) and X4 strains bind CXCR4 and preferentially infect T cells (T-tropic).
- M-tropic dominant in 90% but over course of illness T-tropic viruses accumulate
- Binding to co-receptor induces conformational change in gp 41 allowing fusion with cell membrane and entry of viral genome into cytoplasm
- In cell RNA → double stranded complementary DNA by reverse transcriptase
- DNA integrated into nucleus → transcribed to RNA. Viral core assembled in cell and buds off from cell membrane - results in cell lysis
5
Q
Description of natural history of HIV infection:
A
- Infection of memory CD4 T cells in mucosal lymphoid tissue
- Mucosal infection → dissemination of virus - dendritic cells in epithelia capture virus and migrate to lymph nodes → virus passed onto other target cells. Viral replication → viraemia
- Individual mounts host response (within 3-7 weeks of exposure) → called seroconversion (manifests as a flu like illness). Virus specific CD8+ cytotoxic T cells develop. Viraemia drops at this point with initial containment and CD4 cells recover a bit
- Chronic infection/latent period → often asymptomatic, destruction of CD4+ T cells in lymphoid tissue continues and levels decline, HIV RNA levels increase (not clear how it escapes immune control). Virus may evolve to reply more on CXCR4 for entry into cell (A/W more rapid decline in CD4+ cells). Patients can develop minor opportunistic infections during this phase
- AIDS - breakdown host defence, dramatic increase viral load, lift-threatening clinic disease (develops after 7-10 years in untreated disease).
6
Q
Tumours associated with HIV infection:
A
- Kaposi sarcoma (see photo) → caused by HHV8 infection, in HIV infected patients tumour is usually widespread - skin, mucous membranes, GI tract, lymph nodes, lungs
- Lymphomas
- Germinal centre B cell hyperplasia → B cell lymphomas with translocations (Burkitt lymphoma - MYC)
- T cell depletion → unchecked EBV KSHV reactivation in latently infected B cells → virus associated B cell lymphomas
- HPV associated cancers (cervix, anus)
7
Q
Features of HIV seroconversion
A
- Fevers, sore throat, lymphadenopathy
- Malaise, myalgia, arthralgia
- Diarrhoea
- Maculopapular rash
- Mouth ulcers
- Rarely meningoencephalitis
8
Q
Examples of focal neurological lesions (on imaging) in HIV
A
- Toxoplasmosis - 50% of cerebral lesions in HIV, presents with constitutional symptoms, headache, confusion
- CT - single/multiple ring enhancing lesions, mass effect
- Co-trim prophylaxis if CD4 <100
- Primary CNS lymphoma - 30% cerebral lesions, CT - single or multiple homogenous enhancing lesions
- TB - least common, single enhancing lesion
Can be difficult to distinguish between toxoplasmosis and lymphoma - generally toxoplasmosis multiple lesions and ring/modular enhacnment, lymphoma often single and homogenous
9
Q
Examples of generalised neurological disease in HIV:
A
- Encephalitis - may be due to CMV or HIV itself
- Cryptococcus - clinical picture of encephalitis
- PML - infection of oligodendrocytes by JC virus, subacute onset - behavioural change, speech/motor/visual impairment. MRI - high signal demyelinating white matter lesions
10
Q
Notes on cryptococcus in HIV infection:
A
- Yeast, C. neoformans neoformans most common. Cryptococcal meningitis majority of HIV associated infection
- LP - raised opening pressure. India ink stain and cryptococcal antigen positive (CRAG)
- LP therapeutic (may need to be repeated)
- Rx: amphoteracin plus flucytosine (5FU) x 1/52, then 8 weeks high dose fluconazole with secondary prophylaxis after until immune reconstitution
11
Q
Opportunistic infections and other disorders in HIV and associated CD4 counts
A
- CD4 count 200-500
- Oral candidiasis
- Shingles
- Hairy leukoplakia (EBV)
- Kaposi sarcoma (HHV-8)
- CD4 count 100-200
- Cryptosporidiosis (usually a self-limiting illness at this stage)
- Cerebral toxoplasmosis
- PML (JV virus)
- PJP
- CD4 count 50-100 cells
- Aspergillosis
- Oesophageal candidiasis
- Cryptococcal meningitis
- Primary CNS lymphoma
- CD4 <50
- CMV retinitis
- Mycobacterium avium
12
Q
Notes on nucleoside reverse transcriptase inhibitors (NRTIs)
A
- Bind to viral reverse transcriptase at deoxynucleotide binding site, blocking DNA synthesis
- Activity against HIV 1 and HIV 2
- Zidovudine (AZT) associated with lipodystrophy, metabolic toxicity, GI side effects
- Abacavir (ABC) associated with hypersensitivity (test for HLA B57*01), CVD risk
- Tenofovir disoproxil fumarate and tenofovir alafenamide
- Lamivudine (3TC) and emtricitabine (FTC)
13
Q
Notes on tenofovir
A
- Administered orally as the prodrug tenofovir alafenamide (TAF) or tenofovir disoproxil fumarate (TDF) → converted to tenofovir diphosphate
- TDF short plasma half life, kidney takes up more tenofovir from blood → more nephrotoxic. Also A/W bone mineral density loss
- TAF → longer plasma half life, less renal exposure, less nephrotoxic
14
Q
Notes on non-neucleoside reverse transcriptase inhibitors (NNRTIs)
A
- Bind viral RT but not at deoxynucleotide binding site, alter conformation of enzyme blocking DNA synthesis. Low barrier to resistance
- No role in HIV-2 infection
- Examples:
- Nevirapine (NVP) → hypersensitivity reactions inc. fatal hepatitis (stop if rash - SJS)
- Efavirenz (EFV) - CNS S/Es in 1st few weeks (sedation, insomnia), rash, deranged LFTs and hyperlipidaemia. Cytochrome P450 inducer.
- Rilpiverine (RPV) → Can prolong QTc
- Delaverdine (DLV) - rash (usually treat through)
- Etravirine (ETR) - rash (usually treat through)
- Doravirine - CYP3A substrate
15
Q
Notes on integrase inhibitors
A
- Inhibit viral integrase preventing integration of viral DNA into host DNA.
- Active against HIV-1 and HIV 2
- A/W w/ more weight gain as a class than other classes
- Particularly rapid reduction in viral load
- Raltegravir (RAL) → rise in CK (cases of rhabdo)
- Elvitegravir (EVG) → needs to be “boosted” with cobistat - potent CYP3A4 inhibitor leading to interactions
- Dolutegravir (DTG) → Headache, depression, possible small increase in NTDs
- Bictegravir (BIC) → Headache, GI SE, avoid dofetilide
21
Q
Risk of transmission with exposure from known HIV positive source who is not on ART therapy
A
22
Q
Post exposure prophylaxis recommendations after non-occupational exposure with known HIV positive source
A
- Recommended for all exposures except receptive/insertive oral sex if source not on treatment or has detectable or unknown viral load
23
Q
PEP recommendations after occupational exposure HIV positive source
A
- Recommend 3 drugs for exposure, can consider two if source known to have undetectable viral load
24
Q
PEP recommendations if non-occupational status with unknown HIV status
A
- Recommend use of 2 drugs generally if source MSM or high prevalence country
25
Q
Eligibility criteria for PREP (pre-exposure prophylaxis)
A
