CPT2: HIV Flashcards
What virus causes HIV?
What is the characterisitics of this virus?
- Human immunodeficiency virus
- Retrovirus - single stranded RNA
A retrovirus is a type of virus that inserts a copy of its RNA genome into the DNA of a host cell that it invades, thus changing the genome of that ce
What can result if HIV is left untreated?
nInfection with HIV (eventually) results in AIDS & AIDS-related illnesses
What are routes of transmission?
Verical or horizontal transmission:
- Horrizontal - person to person transmission
- Vertical - Mother to child
Horizontal Transmission
- Sexual intercourse without condom
- Blood contamination
- Sharing injection equipment
- Contaminated blood transfusions or organ transplants
Verical Transmission:
- Breast Feeding
- Prenattaly during labour
- Why have cases in HIV decreased
- What have HIV deaths decreased?
- Better education, early treatment
- Better and more affordable medication
What is normally checked after a newly diagnosed HIV?
What are normal levels?
What do levels tell?
- CB4 is checked to measure immune status
- Normal - 800-1500 cells/mm3
Less than 350 cells/mm3 - Risk of developing AIDs related illness and mortality higher
What is the united nations aid groups aim?
The United Nations AIDS group. Has come up with a target called 1990 nineteen.
The aim is to have 90 percent of people living with HIV. Being diagnosed. Ninety percent of those who are diagnosed receiving antiretroviral therapy. And 90 percent of those will have an undetectable viral load.
What is the life expectancy of someone with HIV and someone without?
If diagnosed with HIV and therapy started early enough life exp is almost the same
What is the structure of HIV like?
Glycoproteins important in receptor (CD4?) attachemnet
What are the main stages in the lifecyle of HIV?
- Binding
- Fusion
- Reverse transcription
- Integration
- Replication
- Assembly
- Budding
Describe each step
How do clinical manifestations differ?
A patient infected with HIV will have a primary HIV infection – seroconversion ie HIV antibody production.
Following this Patients classified into 3 groups:
- Asymptomatic
- Symptomatic – specific & non-specific symptoms
- AIDS – AIDS-defining illness
Clinical manifestations depend on group patient is classed into.
Describe the infection process
Patient infected at week 0. The body doesnt start producing HIV until about 3 weeks. This period is called the window period - HIV test may be negative but patient is still being infected.
Viral starts replicating and viral load rises and CD4 falls and by week 6 the viral load has peaked. The patient has developed primary HIV or seroconversion illness. This is a non-specific illness with symptoms e.g. sore throat, rash (improve in few day), cold, lymphones enlarged.
By week 9 HIV levels are low and CD4 rising again - the immune system has produced AB and is fighting the infection.
Patient enters latency period - immune system has virus uncontrol.
Overtime virus mutations so HIV load raises again and CD4 decreases. The immune systes AB are no longer effective. Patient experiences non-specific symptoms and is called a clinical indicator disease.
If CD4 levels lower below 350 cells/mm3 then they are at risk of developing AID related illness and dying.
What are other clinical indicator illnesses?
Herpes Zoster, Psorasis, oral thrush, STDs
What monitoring is involved in patients with HIV?
- Initial diagnosis
- CD4 count (cells/mm3)
- (normal: 800-1500 cells/mm3)
- Plasma viral load (copies/ml)
- Surrogate markers of disease progression & to measure efficacy of treatment
- Routine monitoring every 3-6 months
- (after viral load undetectable - less than 36copies/ml)
- For first few months monitor closesly until plasma viral load becomes undetectable
Who does the BHIVA (2015) reccomend treatment too?
- All people diagnosed with chronic HIV
- All people presenting with AIDS-defining illnesses or co-infections
- All patients diagnosed with primary HIV infection should be offered treatment
- All pregnant women diagnosed with HIV
What are goals of HIV treatment?
- Suppress viral replication & maintain suppression for as long as possible
- Prevent deterioration of immune system
- Restore immune system
- Preventing and/or treating opportunistic infections
- Improve quality & quantity of life
What are other uses for antiretroviral therapy?
- PEP (Post exposure prophylaxis)
- Given to people who have bcome exposed to HIV following idealisitic? injury
- 2.PEPSE (Post exposure prophylaxis following sexual exposure)
- Given after Rape, incest, discordant couples whose barrier protection failed
- 3.PrEP (Pre-exposure prophylaxis)
- Given to people who are knowingly goinf to be exposed to HIV
PEP and PEPSE: 3 antiretro-viral drug therapy for 28days
prEP: 2 drug regime
What are examples of Antiretroviral treatments?
- Nucleoside (or nucleotide) reverse transcriptase inhibitors (NRTIs)
- Non-nucleoside reverse transcriptase inhibitors (NNRTIs)
- Protease inhibitors
- Entry inhibitor
- Integrase inhibitors
What is antiretroviral treatment cART?
What is important to counsel the patient on?
- Combination treatment - cART
- 2 NRTIs + 1 Third agent(first line therapy)
- NRTI backbones to prevent resistance to thirdline
- Third agent can be Protease inhibitor, integrase inhibitor or RTI
- Life long treatment – concordance is important
- Compliance is essential to ↓ development of resistance
- HIV replication is inhibited & presence of HIV RNA is reduced
What do the BARTA reccomend as first line treatment
How do NRTIs work?
What are examples?
- Emtricitabine, abacavir, lamivudine, didanosine, stavudine, zidovudine (nucleoside)
- Tenofovir (nucleotide)
Tenofovir normally pairs with Emtricitabine
Abcavir normally pairs with lamivudine
- Nucleosides require intracellular phosphorylation to active form
- Halt viral DNA synthesis by competing with cellular substrates. They become incoperated into the copying process and block further copting by reverse transcriptase
Side effects of NRTIs?
- nAbacavir – hypersensitivity reactions in patients who are HLA-B5701 positive (see BNF warnings)
nRenal side effects (eg Fanconi) with tenofovir
nTwo types of tenofovir – disoproxil and alafenamide (lower doses so less renal side effects)
Mechanism of action of NNRTIs?
Examples
Active against?
Irreversibily bind to alternative site to active site on reverse transcripase and alter conformation of active site. This inhibits further polymerisation by reverse transcriptase
- Efavirenz, nevirapine, etravirine, rilpivirine, doravirine*
- Active against HIV-1 but not subtype HIV-2 (prevalent mainly in West Africa)
Side effects of NNRTIs?
- Nevirapine – associated with hepatotoxicity & rash, including Steven-Johnson syndrome
- Efavirenz – nightmares, insomnia, low mood (not really used now)
- Etravirine – hypersensitivity reactions
What role do NNRTIs play in HIV treatment
Usually used in combo with backbone NRTIs
(Usually etravirine or Rilpirivine)
What is the mode of action of Protease inhibitors?
Examples - which is most commonly used?
- Darunavir, atazanavir, lopinavir, ritonavir
- Selectively bind & inhibit HIV protease breaking down HIV protein to form mature HIV. Inhibition leads to deformed HIV particles and reduced infectious capacity
PI:
- Metabolised by?
- What does Darunavir require?
- What are associated side effects?
- metabolised via CYP 450 enzyme system
- “boosting” with low dose ritonavir or cobicistat
- associated with metabolic effects & lipodystrophy
- drug treatment of hyperlipidaemia may be required
What is the mode of action of intergrase inhibitors?
Examples?
Inhibit intergase protein responsible for the incoperation of HIV DNA into the CD4 genome
- Latest addition to ART
- Currently being recommended in combination with a nucleoside backbone (2 NRTI)
- Four integrase inhibitors on the market are raltegravir, elvitegravir, dolutegravir, bictegravir
- Only elvitegravir needs boosted by a non-organic compound called cobicistat
Examples of entry inhibitors?
Generic mechanism
Prevent attachment and fusion of HIV envolope an dCD4 cell membrane
- Enfuviritide
- Ibalizumab
Mechanism of Enfuvirtide?
Route of admin?
Used in?
- Binds to segment of HIV gp41 of the CD4 receptor → prevents conformational changes required for fusion of viral & cellular membranes
- Heavily “treatment-experienced” patients – multi-drug resistant HIV
- Patients intolerant to other antiretrovirals
- bd subcutaneous injection
- Rarely used in current regimens
MEchanism of Ibalizumab
Route?
Used for?
- Monoclonal antibody that binds to the CD4 receptor so that when gp120 binds to it, the receptor does not become activated
- Has to be given intravenously every two weeks
- Used for multidrug resistant HIV
What do co-receptors do?
HIV attaches to CD4 receptor. To bring the virus down for dusion another co-receptor is required.
2 options: CCR5 (found in newly infected patients) or CXCR4 (found in later infected patients)
Example of co-receptor inhibitor?
Mechanism?
used in?
- Maraviroc
- CCR5 inhibitor
- Used in heavily experienced patients
- Viral tropism testing required prior to initiation of therapy
- If CXCR4 used then not suitable
- Rarely used
When might therapy need to be switched?
nChange to new regimen if plasma viral concentration increases or clinical condition deteriorates, or patient intolerant of treatment
nChoice based on resistance assay or patient preference
Complications arising for HIV infections?
- Opportunistic infection – Pneumoystis jiroveci pneumonia (formerly PCP), candidiasis, cryptococcal meningitis , Mycobacterial infection, CMV retinitis
- Co-infections – Hepatitis B, C, syphilis, gonorrhoea
- Malignancies – non- Hodgkins lymphoma, Kaposi’s sarcoma
- (Which are uncommon in immunocompetent population)
- HIV encephalopathy
- HIV associated nephropathy (HIVAN)
- Management of complications – treat then prophylaxis of opportunistic infection/disease
Complications of using ART?
- Metabolic syndrome
- Ischaemic heart disease
- Osteoporosis
- Hypogonadism
- Early ageing
