HIV/AIDS Flashcards
1
Q
What is the role of pharmacists in community and hospital practise?
A
- Identify and prevent potential drug interactions
- Help manage medication side effects
- Understand and optimize management of co-morbidities/conditions
- Understand the need for uninterrupted supply of antiretroviral therapy (consequences - resistance)
- Communicate with the patients’ healthcare team (HIV specialist, family doctor, nurse, pharmacist, dietician, social worker, support worker and etc)
- Understand that YOU are also a part of the patients’ healthcare team
2
Q
What is HIV?
A
Human Immunodeficiency Virus
- Retrovirus
- HIV-1 and HIV-2
- Chronic infection results in the progressive destruction of CD4+ T lymphocytes (crucial for the normal function of the human immune system)
3
Q
What is AIDS?
A
Acquired ImmunoDeficiency Syndrome
- Person is HIV+ AND
- has a CD4+ cell count below 200 or
- CD4+ cells account for fewer than 14% of all lymphocytes or
- Has been diagnosed with one or more of the AIDS-defining illnesses
4
Q
_____ cells are the target of HIV
A
CD4
-HIV interacts with CD4 receptors, invades - replicates - destroys CD4 cells = CD4 depletion
5
Q
How are CD4 cells a part of the immune system?
A
CD4 cells direct and activate immune response
-depletion of CD4 = degradation of immune function
6
Q
What is HAART?
A
Highly Active AntiRetroviral Therapy
7
Q
What is cART?
A
combination AntiRetroviral Therapy
8
Q
How many antiretrovirals should HIV patients be taking?
A
3 or more antiretrovirals used in combination for the purpose of minimizing resistance and maximizing antivirologic and immune response
9
Q
HIV is a chronic viral infection that targets ____ cells and degrades the immune system and without treatment results in death
A
CD4
10
Q
______ treatment with antiretrovirals decreases mortality and morbidity
A
Combination
11
Q
Describe the viral transmission of HIV
A
contact with infectious body fluids (i.e. blood, semen, vaginal secretions, breast milk)
12
Q
Describe the primary HIV infection
A
- Also called acute HIV infection or acute seroconversion syndrome
- Symptoms last about 2 weeks and include fever, sore throat, fatigue, weight loss, myalgia, rash, N, V, D, lymphadenopathy, night sweats, aseptic meningitis (fever, headache, photophobia, stiff, neck) may be present in 25% of presenting cases
- HIV viral load
- Persistent decrease in CD4 lymphocytes
13
Q
What is the seroconversion?
A
development of HIV antibody
14
Q
What is chronic asymptomatic HIV infection?
A
viral replication are more controlled by immune response
15
Q
Define AIDS
A
- CD4 cell count < 200 regardless of the presence or absence of symptoms
- AIDS-defining illness regardless of CD4 cell count
16
Q
Define Advanced HIV infection
A
CD4 count < 50
17
Q
What CD4 cell count causes a high risk of opportunistic infections?
A
< 200
18
Q
What are the main routes of transmission?
A
- Sex
- IV drugs
- Perinatal (mother to child transmission)
Sex, Drugs, and Rock a Bye Baby
19
Q
What are the 2 most common types of sexual transmission of HIV
A
- Receptive anal
- Receptive vaginal
20
Q
What are other types of sexual transmission?
A
- Insertive anal
- Insertive vaginal
- Oral (low risk, Receptive > insertive)
21
Q
What are some factors that would increase risk of transmission?
A
- Increased viral load
- Vaginal bleeding during intercourse
- Genital ulcers
- STI
- Lack of circumcision in males
- Genetic and host factors
22
Q
What decreases the risk of transmission?
A
- Condoms
- Treatment of STIs
- Male circumcision
23
Q
Mother to Child (vertical) transmission:
Overall risk of vertical transmission in _____ of drug therapy and other interventions
A
20-25%
24
Q
Mother to Child (vertical) transmission:
50-70% of transmission occurs when ?
A
just before or during birth process/delivery
*in utero transmission is rare
25
Mother to Child (vertical) transmission:
| Can virus be transmitted in breast milk?
you betcha
26
Mother to Child (vertical) transmission:
In HIV patients who have babies, it is recommended that they exclusively ________ _____ their baby if have clean water available to do so
formula feed
27
Mother to Child (vertical) transmission:
How do we prevent this?
- Treat mother with antiretroviral therapy DURING pregnancy (may want to delay initiation until after the first trimester)
- Antiretroviral treatment DURING labor & delivery and TO BABY post delivery
28
What drug is given to mother during labour & delivery
IV Zidovudine
29
What drug is given to baby for first 6 weeks?
Oral Zidovudine
30
Mother to Child (vertical) transmission:
May require C-section if ?
viral load too high (>1000 copies/mL)
31
Describe IV transmission
- IV injection with used needles and other injection paraphernalia
- Needle stick injuries (occupational & non-occupational)
- Mucosal exposure to blood
- Recipient of blood products
- Recipient of organ transplant
32
How can you decrease the risk of parenteral transmission ?
- Free needle exchange programs
- Not sharing injection parphernalia
- Sterilize equipment (bleach)
- Safe disposing of used paraphernalia
- Use of Post Exposure Prophylaxis (PEP)
33
What 4 treatment strategies are known to prolong survival?
- ART
- PCP prophylaxis
- MAC prophylaxis
- Care by a healthcare team specializing in HIV
34
List the stages of HIV infection
Stages of HIV infection include transmission, primary infection, chronic infection
35
HIV is transmitted through 3 main exposure routes, what are they?
- sexual
- parenteral
- perinatal
36
What methods can decrease the risk of transmission?
condom use, not sharing IV drug equipment and treatment during pregnancy
37
List the 9 steps of HIV viral entry/replication
1) Binding
2) Fusion
3) Uncoating
4) Reverse Transcription
5) Genome Integration
6) Genome Replication
7) Protein Synthesis
8) Protein Cleavage
9) Virus Assembly and spread
*slide 20
38
What are ARV's known as?
Birth control for HIV
- Prevents new infectious virus from being made IF taken daily and able to achieve and maintain therapeutic blood levels.
- If ARV stopped or missed, nothing preventing for new virus being made
39
___ is like an intruder in a factory
HIV
40
Describe how HIV enters
HIV enters the CD4 factor, hijacks the production line to make viral components instead of CD4 components resulting in thousand/millions of new virus
41
List the 6 classes of antiretrovirals
1-Nucleoside/tide Reverse Transcriptase Inhibitors (NRTIs) "nukes"
2-Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTIs) "non-nukes"
3-Protease Inhibitors (PIs)
4-Integrase Strand Transfer Inhibitors (INSTIs)
5-Fusion Inhibitors
6-CCR5 Receptor Antagonists
42
see slide 23
okay
43
What is an STR?
Single tablet regimens (has 3 antiretrovirals in a single pill)
44
Cobicistat acts as a _____
booster
45
Antiretrovirals work at different parts of the HIV life cycle to _____ _______
disrupt replication
46
Currently there are __ classes of antiretrovirals with different mechanisms of action
6
47
Many antiretrovirals available and can exist as single entity, single tablet regimen or co-formulated products but need at least _ antiretroviral drugs used in combination (low dose booster does not count)
3
48
Goals of therapy for HIV treatment
- Reduce HIV-associated morbidity and prolong the duration and quality of survival
- Restore and preserve immunologic function using antiretroviral therapy
- Maximally and durably suppress plasma HIV viral load
- Prevent HIV transmission
49
What are the 2 markers of disease progression?
1) Virus (viral load) - HIV RNA in blood
- Average viral burden (without therapy) is 30,000 to 50,000 RNA copies/mL but huge range
- Lives in/targets the lymphoid cells (CD4+, T cells)
- High capacity for replication and subsequent destruction of CD4+ cells (up to 1 billion per day)
2) CD4+ T cell lymphocyte counts and percentage
- Normal CD4+ count in non-HIV patient = 800-1050
- The average rate of decline of CD4 cells is about 50 cell/year after first year of infection
- Increased risk of morbidity at 200 cells
- <50 cells medium survival = 12-18 months without treatment
50
Benefits of starting ART earlier rather than later
- increase potency, durability, simplicity, safety of current regimens
- decrease emergence of resistance
- decrease toxicity with earlier therapy
- increase subsequent treatment options
- risk of uncontrolled viremia at all CD4+ cell count levels
- decrease transmission
51
Describe the patient evaluation prior to initiation of HAART
Physical:
- Evidence of symptomatic HIV disease
- Evidence of opportunistic infections
- Infections, weight loss, fevers, malaise, diarrhea, cognitive problems, neuropathy, visual problems, oral lesions, skin rashes or lesions, and any chronic complaints
Psychosocial:
-Substance abuse, housing, access to medications, psychiatric
Laboratory:
-CD4+ count, VL, serology for Hepatitis A, B, C toxoplasmosis, CBC, Chemistry, BUN, CSR, s-glucose, LFTs, cholesterol
52
What test is done before Abacavir can be administered?
HLA *B5701
-for Abacavir associated hypersensitivity reaction (fever, rash, fatigue, nausea, vomiting, respiratory symptoms, headache, arthralgia, increased CK, increased LFTs) - can be life-threatening
53
List 2 boosters
Low dose Ritonavir or Cobicistat
54
Describe the 3 types of regimens
- 2 NRTIs and 1 NNRTI
- 2 NRTIs and 1 PI
- 2 NRTIs and INSTI
55
We want to individualize regimen based on what?
- HIV characteristics (genotype for drug resistance)
| - Patient (co-morbidiites, side effect profile, preference)
56
Describe the recommended initial regimen for most people with HIV (INSTI-based)
INSTI-based:
1) Raltegravir & Tenofovir DF or AF + Emtricitabine
2) Dolutegravir & Tenofovir DF or AF + Emtricitabine
3) Dolutegravir & Abacavir + Lamivudine
4) Elvitegravir/Cobicistat/Tenofovir DF or AF/Emtricitabine
* Only for patients who are HLA B5701 negative
57
________ and ________ can be used interchangeably for each other
*if you develop resistance for one, can't use the other
Emtricitabine and Lamivudine
58
Describe the recommended initial regimen for certain clinical situations with HIV (NNRTI-based)
1) Efavirnez/Tenofovir DF/Emtricitabine
2) Efavirnez + Tenofovir AF/Emtricitabine
3) Rilpivirine/Tenofovir DF or AF/Emtricitabine (if VL < 100 000 and CD4 > 200)
59
Describe the recommended initial regimen for certain clinical situations with HIV (INSTI-based)
Raltegravir + Abacavir/Lamivudine
60
Describe the recommended initial regimen for certain clinical situations with HIV (PI-based)
1) Atazanavir + Ritonavir or Cobicistat once daily
&
TDF or TAF/Emtricitabine
```
2) Darunavir + Ritonavir
Or
Darunavir/Cobicistat
&
Abacavir/Lamivudine
```
3) Darunavir/Cobicistat
&
TDF or TAF/Emtricitabine
61
DF
Disoproxil Fumarate
62
AF
Alafenamide
63
_______ can only be used if HLA B5701 negative
Abacavir
64
______ should not be used in patients who require > 20 mg omeprazole/equivalent per day
Atazanavir
65
What are some factors to consider for selection of ARVs
- drug resistance
- viral load
- CD4 count
- HLA B5701
- co-morbidities
- genetic predisposition
- drug interactions
- pill burden
- patient preference
- side effect profile
- ability to swallow/formulation (liquid/crush/split)
66
List 2 advantages of INSTI (integrase strand transfer inhibitors)
- NNRTI and PI options preserved for future use
| - Less negative effects on lipids
67
List advantages/disadvantages of Raltegravir
INSTI (integrase strand transfer inhibitors)
Advantage: Not metabolized through CYP and less likely to have drug interactions
Disadvantage:
- BID dosing
- Low genetic barrier to develop drug resistance (single key mutation wipes out activity)
68
List advantages/disadvantages of Elvitegravir
INSTI (integrase strand transfer inhibitors)
Advantage: Once daily dosing and available as STR (single tablet regimen)
Disadvantage:
- Needs booster (Cobicistat)
- Potential for CYP drug interactions
- Low genetic barrier to developing drug resistance
- Only available as STR (*guidelines for renal insufficiency)
69
List advantages/disadvantages of Dolutegravir
INSTI (integrase strand transfer inhibitors)
Advantage:
- Once daily dosing
- Highest genetic barrier of INSTI class
Disadvantage:
- UGT substrate; potential for drug interactions
- Oral absorption can be reduced by simultaneous administration with products containing polyvalent cations (Ca, Mg, Al, Fe)
70
List advantages of protease inhibitors
- Higher genetic barrier for resistance - multiple mutations to cover resistance
- PI resistance uncommon with failure (boosted PIs)
71
List disadvantages of protease inhibitors
- Metabolic complications (fat maldistribution, dyslipidemia, insulin resistance)
- Gastrointestinal adverse effects
- Greater potential for drug interactions (CYP450) especially with Ritonavir (boosted regimens)
72
List advantages of NNRTIs (non-nucleoside reverse transcriptase inhibitors)
- Less dyslipidemia and fatmaldistribution then PI based regimen
- Long half-life
- PI and INSTI options preserved for future use
73
List disadvantages of NNRTIs (non-nucleoside reverse transcriptase inhibitors)
- Low genetic barrier (single mutation can confer class resistance)
- Skin rash
- Hepatotoxicity (Nevirapine)
- CNS effects (Efavirenz)
- Potential for CYP450 drug interactions
- Transmitted resistance to NNRTis more common than resistance to PI
74
List 2 side effects of ALL NRTIs
-Lactic acidosis and hepatic steatosis
Rare: higher incidence with older/no longer used compared to newer NRTIs
-Lipodystrophy (a change in body fat distribution)
Uncommon: significantly higher incidence with older/no longer used NRTIs
75
Describe Lipodystrophy
- Mechanism not understood
- May be associated with dyslipidemia, insulin resistance, lactic acidosis
- Switch to other agents may slow progression
76
List adverse effects of Abacavir (NRTI)
- Hypersensitivity reaction 3-8%, can be fatal. HLA *B5701 testing prior to treatment (next to zero risk if negative, don't use if positive)
- Headache
- GI intolerance.
77
List adverse effects of Tenofovir (NRTI)
- Headache
- GI intolerance
- Renal impairment (use with caution in patients with pre-existing impairment or risk of renal impairment)
- Usually well tolerated
78
List adverse effects of Zidovudine (NRTI)
- Headache
- GI intolerance
- Bone marrow suppression
- Lipoatrophy
79
List adverse effects of Emtricitabine, Lamivudine (NRTI)
- GI intolerance
- headache
- potential hyperpigmentation in patients with darker complexions or ethnicities
80
Adverse effects of Raltegravir (INSTIs)
- insomnia
- headache
- nausea
- fatigue
- creatine kinase (CK) elevation
- rhabdomyolysis (dark urine in the absence of dehydration - indicative of rhabdomyolysis
81
Adverse effects of Elvitegravir (INSTIs)
- nausea
- diarrhea
- headache
82
Adverse effects of Dolutegravir (INSTIs)
- nausea
- diarrhea
- headache
- insomnia
83
Monitoring for INSTIs
if symptoms of rhabdomyolysis/myositis (unexplained muscle pain, tea coloured urine) check serum CK levels
84
Adverse effects of ALL PIs
- Hyperlipidemia (differs between different PIs and also related to amount of Ritonavir)
- Insulin resistance and diabetes
- Lipodystrophy
- Elevated liver function tests
- Drug-drug interactions
85
Adverse effects of Atazanavir (PI)
Hyperbilirubinemia (may manifest as jaundice/scleral icterus)
Tell patient to watch for yellowness of skin or eyes
86
Adverse effects of Darunavir (PI)
Rash, food requirement, GI intolerance
87
Adverse effects of Lopinavir/ritonavir (PI)
- GI intolerance
- diarrhea
- dyslipidemia
88
Adverse effects of Ritonavir (PI)
- GI intolerance
- hepatitis/elevated liver enzymes
- diarrhea
89
Ritonavir is only used for _______ other PIs at 100-200 mg/day
boosting
90
Adverse effects of Efavirenz (NNRTI)
- CNS/neuropsychiatric: feeling of dissociated, disconnected, nightmares, vivid dreams, insomnia, depression, "fuzzy feeling", "hung-over", impaired concentration, agitation, euphoria
- Onset: first day - 6 weeks
- Incidence: 50% (but need to discontinue in about 2%)
- Usually SE get better over time (6 weeks)
- Take at HS "sleep through the side effect", on an empty stomach (avoid elevated levels)
- Patient counselling and support is important
*Teratogenic in nonhuman primates
91
Adverse effects Nevirapine (NNRTI)
Hepatotoxicity (may be severe and life-threatening)
- Increased risk in women CD4 > 250 and men CD4 > 400
- Greatest risk during the first 6 weeks
- Symptoms: often non-specific, including fatigue, malaise, anorexia, nausea, jaundice
- Rash
92
Monitoring of Nevirapine? (NNRTI)
- Transaminases (baseline, at 2 weeks, 4 weeks then monthly for first 18 weeks)
- Rash
93
_______ is an example of a second generation NNRTI
Etavirine
94
Describe the MOA of Etavirine (second generation NNRTI)
binds to reverse transcriptase and inhibits replication
95
Dose of Etavirine (second generation NNRTI)
200mg BID (or if no significant mutations then 400mg once daily)
96
Place in therapy of Etavirine (second generation NNRTI)?
Treatment experienced patients with resistance to other classes of ARVs including NNRTIs
97
Adverse drug reactions of Etavirine (second generation NNRTI)
- rash
- nausea
- less CNS effects (vivid dreams, dizziness) than with Efavirenz
98
MOA of CCR5 receptor antagonists
binds to CCR5 co-receptor of CD4 cell preventing entry into cell
PREVENTS ENTRY INTO CELL
99
CCR5 receptor antagonists:
| indication ?
treatment experienced patients with resistance to other classes of ARBs
100
CCR5 receptor antagonists:
| Requires _____ test (not available locally)
tropism
101
CCR5 receptor antagonists:
| Only effective if ??
virus uses CCR5 EXCLUSIVELY (won't work if CXCR4 or both CCR5 and CXCR4)
102
CCR5 receptor antagonists:
| Side effects ?
cough, rash, upper respiratory infection, fever
103
Give an example of a fusion inhibitor
Enfuvirtide (T-20)
this is the only injectable antiviral at this point !!
104
```
Fusion Inhibitors (ex. Enfuvirtide T-20):
MOA
```
binds to gp41 and prevents fusion of viral and cellular membranes
105
```
Fusion Inhibitors (ex. Enfuvirtide T-20):
Route and frequency?
```
SC injection BID
106
```
Fusion Inhibitors (ex. Enfuvirtide T-20):
Place in therapy ?
```
Treatment experienced patients with resistance to other classes of ARVs
107
Fusion Inhibitors (ex. Enfuvirtide T-20):
SE ?
- local injection site reaction is common (95%)
- pruritis
- pain/discomfort
- nodule/cyst formation
- induration
- ecchymosis
108
Is anyone on a Fusion Inhibitors (ex. Enfuvirtide T-20): in manitoba?
No:
- no one wants to inject themselves if they don't have to
- BID dosing
- lots of adverse reactions
109
List advantages of Triumeq (Dolutegravir/Abacavir/Lamivudine)
-a STR
- Single tablet regimen
- Less negative lipid effects compared to PI and NNRTI classes
- Potentially higher genetic resistance compared to other INSTI and NNRTI
- No pharmacoenhancer - less potential for drug interactions
- No food requirement for absorption (good for homeless ppl who may not have access to food)
110
List disadvantages of Triumeq (Dolutegravir/Abacavir/Lamivudine)
-a STR
-Need B5701 test result prior to use due to Abacavir
-If taken on empty stomach, space apart from polyvalent cation containing products (Mg, Ca, Fe including multivitamins or oral antacids)
(space apart 2hrs before or 6hrs after)
* not worried about calcium in dietary products
* more concerned with the high concentration present in medicines
111
Stribild
Genvoya
(only differ between salt of Tenofovir)
Advantages?
Less negative lipid effects compared to PI and NNRTI classes
112
Stribild
Genvoya
(only differ between salt of Tenofovir)
Disadvantages?
- Potential drug interactions w Cobicistat boosting
- Food requirement for optimal absorption
- Lower genetic barrier to drug resistance than PI class
- Co-formulated w Tenofovir DF or AF
- Cannot start in patients with renal insufficiency CrCl < 70 for TDF
- Cannot start in patients with renal insufficiency CrCl < 30 for TAF
113
Advantages of:
Darunavir (boosted with Ritonavir or Cobicistat and 2 NRTIs)
- no evidence of PI resistance mutations with virology failure when used as the initial PI
- HIGHEST genetic barrier to drug resistance
114
Disadvantages of:
Darunavir (boosted with Ritonavir or Cobicistat and 2 NRTIs)
- Rash
- Negative lipid effects (compared to INSTI)
- Pill burden greater than NNRTI or INSTI regimen (2-3 pills/day)
- Food requirement for optimal absorption
- Potential drug interactions with Ritonavir or Cobicistat boosting
- GI intolerance due to Ritonavir or Cobicistat
115
Advantages of:
2 Pill Regimen:
Dolutegravir + Tenofovir DF or AF/Emtricitabine
- Higher genetic barrier to drug resistance compared to NNRTi and INSTi classes; comparable to PI class
- Can use if unknown or positive HLA B5701 status
- NO booster = less potential drug interactions with CYP 3A4 drugs
- NO food requirement for absorption
- Can crush, split to administer
116
Disadvantages of:
2 Pill Regimen:
Dolutegravir + Tenofovir DF or AF/Emtricitabine
- 2 pills
- Drug interactions with divalent cations - space apart or take w food
- Interacts with metformin (increases serum levels)
- Dolutegravir - higher reports of insomnia (7%) compared to other INSTIs
117
List some short term ADRs
- N, V, D
- headache
- rash/allergies
- CNS effects (dizzy, drowsiness, vivid dreams, headache)
118
List some long term ADRs
- Bone marrow suppresion
- Mitochondrial toxicity
- Metabolic complications
- Nephrotoxicity
- Hepatotoxicity
119
How can we manage GI side effects
- Take w food if possible
- HS dosing
- Antiemetics (Dimenhydrinate, metoclopramide, ondansetron/granisetron)
- Consider dietary issues
- Antidiarrheals (loperamide, calcium carbonate, pancreatic enzymes, codeine)
120
3-5% of HIV patients develop ______
diabetes
121
Diabetes:
| Onset ?
weeks to months
122
Type __ DM = insulin resistance & decreases insulin production
2
123
Risk factors for HIV patients developing diabetes?
- underlying hyperglycemia
| - family history
124
All ____ associated with hyperglycemia
PIs
125
How do we manage Hyperglycemia?
- Diet & Exercise
- Consider switching of PI based regimen
- Treatment with oral hypoglycemics
- Monitor FPG @ baseline, 3-6 months, then annually, and A1C)
126
Onset of hyperlipidemia?
3 months
127
Describe the order in which agents have highest chance of causing hyperlipidemia?
Boosted PI > NNRTI > INSTI
128
Consequences of hyperlipidemia?
CV disease, Pancreatitis
129
Management of hyperlipidemia in those with HIV
- minimize CVD risks (ex. smoking)
- pharmacologic treatment with either Atorvastatin 10 mg daily, Pravastatin 20 mg daily, or Rosuvastatin
- Statin x 4 months then add vibrate if needed
130
Monitoring of hyperlipidemia?
lipid profile @ baseline, 3-6 months after initiation then at least annually
131
List 2 potential consequences of antiretroviral interactions
1) Decreased antiretroviral activity
- Risk of sub therapeutic drug levels, inadequate viral suppression, resistance, disease progression
2) Increased risk of toxicity
- May lead to morbidity, non-adherence, drug discontinuation
132
List 1 desirable drug interaction for HIV patients
Exploiting drug interaction to enhance/improve therapy
- Ritonavir and Covicistat strong inhibitor of CYP450 3A4
- Ritonavir used at low dose 100-200 mg/day to "boost" concomitant PI serum levels
- Cobicistat used at 150 mg
- Higher trough levels
- Allows for less frequent dosing
133
Describe the interaction between:
Antacids (PPIs, and H2B) and Atazanavir
significant decrease in Atazanavir bioavailability - pH dependent (max 20mg opemrazole equivalent daily)
134
Describe the interaction between:
Boosted PI and Statin
increased statin levels and effect - may need to decrease dose
135
Describe the interaction between:
HIV meds and products with divalent cations
Chelation Ca, Fe, Al, Mg
136
Describe the interaction between:
HIV meds and integrase inhibitors
space apart 2 hours before or 6 hours after or give with food
137
Describe the interaction between:
Warfarin & Etravirine
May cause elevated levels leading to toxic adverse effects
Etravirine inhibits warfarin metabolism
138
Describe the interaction between:
Ritonavir/Cobicistat & Steroids (ex. fluticasone)
- increases fluticasone plasma concentration and decreases plasma cortisol concentration
- Recommend Beclomethasone
**Key point: do not withhold/delay systemic steroid for treatment of acute disease - asthma or COPD
139
Describe the interaction between:
Ritonavir/Cobicistat & Statins
-increases plasma concentrations of atorvastatin and increases risk of myopathy and rhabdomyolysis
Manage: use lowest dose possible and monitor for signs & symptoms of myopathy and rhabdomyolysis (muscle pain, tenderness, weakness) and consider monitoring CK levels if signs or symptoms appear
140
What is the optimal response with HAART?
Decrease viral load
Increase CD4 count
*requires adherence
141
When should you monitor HIV RNA viral load?
- At baseline and 2-8 weeks after treatment or change in therapy (should be minimum decrease of 1 log10 copies/mL
- Repeat every 3-4 months on stable ART
*Goal is to reduce HIV VL < 20 copies/mL
142
When should you monitor CD4+ T cell count?
- At baseline and every 3-4 months
| - May decrease frequency if on stable suppressive ART
143
When should you monitor CBC?
- At baseline
| - Repeat every 3-4 months
144
When should you monitor electrolytes?
- At baseline
| - Repeat every 3-4 months
145
When should you monitor liver function, LFTs, and albumin?
- At baseline and at 4-6 weeks
| - Repeat every 3-4 months on stable ART
146
When should you monitor Kidney function, BUN, S-Cr?
- At baseline
| - Repeat every 3-4 months on stable ART
147
What should you monitor for glucose intolerance?
monitor blood glucose and A1C
148
What should you monitor for lipids?
total cholesterol, LDL, HDL, Triglycerides
149
What should you monitor for fat redistribution?
- no routine tests
| - some measure waist to hip ratio
150
What should you monitor for lactic acidosis?
If symptoms - monitor lactic acid levels, some monitor anion gap
151
List 3 Limitations to treatment safety and efficacy
1) Adherence
2) Drug interactions
3) Adverse effects
152
When should we switch/modify treatment? (4)
1) Virologic failure
2) Toxicity
3) Difficulty adhering to the regimen
4) Current antiretroviral regimen is suboptimal
153
What defines virologic failure?
The failure to achieve a viral load < 50 copies/mL by 48 weeks or any sustained return of the viral load to > 50 copies/mL
154
Causes of virologic failure?
- Incomplete adherence
- Inadequate antiretroviral potency
- The development of drug resistance
- Failure of the drugs to reach the target site
155
Describe enhancing adherence (patient-focused)
- Treat depression & substance abuse
- Social support
- Determine patient readiness
- Involve patient in selection and scheduling
- Educate about ADRs
156
Describe enhancing adherence (treatment focused)
- Simplify regimen
- Individualize regimen
- Offer medication "run through"
- Offer adherence aids (calendars, beepers, pill organizers, bubble packing)
- Manage ADRs aggressively
157
Describe a Medication run through (NOT A RUN DOWN JIM LOL)
Discuss how they think it would be fit into their daily life:
- time of day
- If best taken with food and how much
- Ensure they have uninterrupted access to their meds
Trouble shooting tips:
-What to do if they are late taking a med, forget taking, vomit or are travelling with medication
158
What is PrEP and describe it.
Pre-Exposure Prophylaxis:
- to prevent acute formation of the virus
- 2 drugs
- Use antiretroviral medication PRIOR to exposure to HIV to protect against infection
- Currently only Tenofovir DF/Emtricitabine approved for use in Canada as daily oral therapy
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What is PEP and describe it.
Post Exposure Prophylaxis:
- 3 drugs
- Use of the combination of 3 antiretrovirals AFTER potential exposure to HIV
- Initiation within 72 hours (ASAP)
- Starter kits in ERs
- 28 day treatment
