25 - HIV Flashcards
1
Q
What is the difference between HIV and AIDS?
A
- HIV = Human Immunodeficiency Virus
- Retrovirus
- HIV-1 is the type in North America
- Chronic infection causing progressive destruction of CD4+ T-lymphocytes (crucial for normal function of human immune system)
- AIDS = Acquired Immunodeficiency Syndrome
- Person is HIV-positive & has CD4+ cell count below 200
- Person can go between having AIDS & not, so try to refrain from using this term; also stigmatizing
2
Q
What is the mechanism of immunologic deficiency for HIV?
A
- CD4 cells are the target of HIV
- HIV interacts w/ CD4 receptors, enters CD4 cell -> replicates -> destroys CD4 cell => CD4 depletion
- CD4 cells direct & activate immune response
- Depletion of CD4 = degradation of immune function; w/o tx will result in death
- Combination tx w/ antiretrovirals decreases mortality & morbidity
- When HIV enters CD4, brings in RNA which is transcribed into DNA & then becomes part of the host DNA, so host is reproducing the virus, making it very hard to treat
3
Q
Stages of HIV infection
A
- Viral transmission – contact w/ infectious body fluids (ex: blood, serum, vaginal secretions, breast milk)
- Urine is sterile, so isn’t transmitted through urine unless blood is present
- Primary/acute HIV infection – sx last ~ 2 weeks (fever, sore throat, fatigue, weight loss, myalgia); high viral load (may > 1,000,000 copies/mL) & persistent decrease in CD4 lymphocytes
- Very severe flu-like sx for 2 weeks, then goes away
- Seroconversion (development of HIV antibody) – 95% convert w/in 6 months
- Chronic asymptomatic HIV infection (viral replication is more controlled by immune response)
- Chronic symptomatic HIV infection
- AIDS – CD4 cell count < 200/mm3 regardless of presence/absence of sx
- Advanced HIV infection – CD4 cell count < 50 cells/mm3
4
Q
Main routes of HIV transmission
A
- Sexual
- Parenteral (intravenous)
- Perinatal or mother-to-child transmission/ vertical
- Think sex, drugs, & rock a bye baby
5
Q
Describe sexual transmission of HIV
A
- Most common = receptive anal & receptive vaginal
- Oral is low risk (only transmit if break in mucous membrane or blood is present)
6
Q
Factors that increase risk of sexual transmission
A
- Increased viral load
- Vaginal bleeding during intercourse
- Genital ulcers
- STI’s
- Lack of circumcision in males
- Genetic & host factors
7
Q
Factors that decrease risk of sexual transmission
A
- Condoms
- Tx of STIs
- Male circumcision
8
Q
Describe vertical transmission of HIV
A
- Overall risk in absence of drug therapy & other interventions ~20-25%
- 50-70% of transmission occurs just before or during birth process/delivery
- In-utero transmission rare
- In resource rich countries, where formula feedings readily available, breast feeding is not recommended
- In resource poor countries, breast feeding recommended b/c formula feeding not feasible
9
Q
Tx for vertical transmission of HIV
A
- Screen for HIV during pregnancy
- Tx mother w/ antiretroviral therapy during pregnancy (pre-exposure prophylaxis PrEP)
- Antiretroviral tx during labour & delivery to mother & to baby post-delivery
- Baby gets antiretrovirals after birth for 4-6 weeks (post-exposure prophylaxis PEP)
10
Q
Describe parenteral tranmission of HIV
A
- Exposure to contaminated blood products (most common = IV injection w/ used needles & other injection paraphernalia)
- Decrease risk of transmission – free needle exchange programs, not sharing injection paraphernalia, & use of PEP
11
Q
What is pre exposure prophylaxis? What is the recommended tx?
A
- Antiretrovirals taken by a person who doesn’t have HIV to prevent HIV before possible exposure
- Tenofovir DF 300 mg/ Emtricitabine 200 mg (Truvada) – 1 tablet PO daily
- Major barrier in MB = cost
- Requires prior and post testing for HVI
12
Q
What is post exposure prophylaxis? What is the recommend tx?
A
- Antiretrovirals taken by person who doesn’t have HIV to prevent HIV infection after possible exposure (occupational or not)
- 28 days course of 3 antiretrovirals started w/in 72 h of exposure
- In MB – 3 day starter kit available through ER & remaining 25 days Rx through community pharmacy ($$$)
13
Q
Four tx strategies known to prolong survival
A
- Antiretroviral therapy
- P. jiroveci prophylaxis (PCP)
- M. avium complex prophylaxis (MAC)
- Care by healthcare team specializing in HIV
14
Q
What are the 6 classes of antiretrovirals? Which 4 are most common?
A
- Protease inhibitor (PIs)*
- Integrase strand transfer inhibitors (INSTIs)*
- Nucleoside reverse transcriptase inhibitor (NRTIs)*
- Non-nucleoside reverse transcriptase inhibitor (NNRTIs)*
- CCR5 receptor antagonist
- Fusion inhibitors
15
Q
Analogies for life cycle of HIV
A
- ARVs = birth control for HIV b/c prevents new infectious virus from being made (if taken daily & able to achieve & maintain therapeutic blood levels)
- HIV like an intruder in a factory (HIV enters CD4 factor, hijacks production line to make viral components instead of CD4 components => thousands/millions of new virus
16
Q
Examples of antiretrovirals from the 4 main classes
A
- NRTIs = tenofovir DF, tenofovir AF, abacavir, emtricitabine, zidovudine
- NNRTIs = efavirenz, etravirine, nevirapine, rilpivirine
- PIs = darunavir + ritonavir; atazanavir + ritonavir; “avir”
- INSTIs = dolutegravir, raltegravir; “gravir”
17
Q
Goals of therapy for HIV
A
- Reduce HIV-associated morbidity & prolong duration & quality of survival
- Restore & preserve immunologic function
- Maximally & durably suppress plasma HIV viral load
- Prevent HIV transmission
18
Q
Surrogate markers of disease progression
A
- Viral load = HIV RNA in blood
- Average viral burden w/o therapy = 30,000-50,000
- CD4+ T cell lymphocyte counts (and %)
- Normal CD4+ count in non-HIV pt = 800-1050 cells/mm3
- Average rate of decline of CD4 cells ~ 50 cells/mm3 per year after first year of infection
- Increased risk of morbidity at 200 cells/mm3
- < 50 cells/mm3 median survival = 12-18 months w/o tx
19
Q
Who is antiretroviral therapy recommended for? When should it be initiated?
A
- Recommended for all HIV-infected individuals to reduce disease progression & for prevention of transmission
- Therapy should be initiated ASAP, but may be deferred on a case-by-case basis
20
Q
Pt evaluation prior to initiation of HAART
A
- Physical – evidence of symptomatic HIV disease, evidence of opportunistic infections, fever, malaise, skin rashes or lesions, etc.
- Psychosocial – substance abuse, housing, access to meds, psychiatric
- Lab – CD4+ count, serology for hep A, B, & C; CBC, BUN, sCr, LFTs, cholesterol (protease inhibitors can worsen cholesterol)
- Certain antiretrovirals will also cure hep B, so if pt is hep B positive would choose a drug that will also treat it
- Other tests – syphilis, tuberculin skin test, chest x-ray, gynecologic exam w/ Pap
- HLA *B5701 – if pt has this allele are at increased risk of having hypersensitivity reaction to abacavir; if can’t do the test then just avoid abacavir
- HIV drug resistance testing – genotyping of virus to look for drug resistant strain
21
Q
Initial tx in tx naïve pt
A
- Combination therapy – usually need at least 3 antiretrovirals (low dose ritonavir or cobicistat for boosting doesn’t count)
- 3 types of regiments
1) 2 NRTIs + 1 NNRTI
2) 2 NRTIs + 1 PI (preferably boosted w/ ritonavir or cobicistat)
3) 2 NRTIs + INSTI - Individualize regimen based on HIV characteristics & pt
22
Q
Recommended initial regimens for most people (based on guidelines)
A
- All have emtricitabine (could also use lamivudine; these 2 considered interchangeable so never used together)
- All have tenofovir DF or AF (AF preferred)
- All have INSTI as 3rd drug due to side effect profile; either raltegravir, dolutegravir, or elvitegravir + cobicistat
23
Q
Factors to consider for selection of ARVs
A
- Drug resistance
- Viral load
- CD4 count (some regimens require CD4 above a certain level)
- HLA B5701
- Co-morbidities (renal function, hep B status)
- Drug interactions
- Pt preference
- Formulation
24
Q
Integrase strand transfer inhibitors - advantages
A
- Less negative effects on lipids
- If unboosted, less potential for drug interactions via CYP
- Raltegravir – not metabolized through CYP, so less likely to have drug interactions
- Dolutegravir – highest genetic barrier of the class
25
Q
INSTI - disadvantages
A
- Raltegravir – low genetic barrier (missing doses can cause virus to generate a mutation, and one mutation will make the virus totally resistant to raltegravir)
- Elvitegravir – needs booster
- Dolutegravir – oral absorption can be reduced by simultaneous administration w/ products containing polyvalent cations
26
Q
INSTI – adverse effects
A
- Raltegravir = insomnia, headache, nausea, fatigue, creatine kinase elevation, rhabdomyolysis, myositis
- Dolutegravir = insomnia
