HIV - Opportunistic Disease Flashcards
Goal for HAART therapy
Reduce HIV-associated morbidity and prolong the duration and quality of survival
Restore and preserve immunologic function
Preserving future therapeutic options
Maximally and durably suppress plasma HIV viral load
(< 20 copies/mL)
Prevent HIV transmission
Truvada = and dosing
tenofovir (TDF) + emtricitabine
QD
Descovy = and dosing
tenofovir (TAF) + emtricitabine
QD
Epzicom = and dosing
abacavir + lamivudine
QD
Combivir = and dosing
zidovudine 300 mg + lamivudine 150 mg
BID
Integrase Strand Transfer Inhibitors (INSTI) list of drugs
raltegravir (Isentress) – RAL
elvitegravir (STRIBILD STR only) – EVG
dolutegravir (Tivicay) – DTG
raltegravir (Isentress) - RAL
400mg BID
elvitegravir (STRIBILD STR only) – EVG
150 mg QD
dolutegravir (Tivicay) – DTG
50 mg QD
Protease Inhibitors list of drugs and what should remember about PI?
atazanavir (Reyataz) – ATV
darunavir (Prezista) – DRV
ritonavir (Norvir) – RTV or r
Most associated with long-term side effects compared to other HIV antivirals
SE includes elevated TG and LDL, insulin resistance, increase fat accumulation , nephrotoxicity (kidney stone), GI disturbances
atazanavir (Reyataz) – ATV
300 mg QD
darunavir (Prezista) – DRV
800 mg QD
ritonavir (Norvir) – RTV or r
100 mg QD
Booster of protease inhibitors
TAKE WITH FOOD
Non-Nucleoside Reverse Transcriptase Inhibitors
efavirenz (Sustiva) – EFV
rilpivirine (Edurant) – RPV
efavirenz (Sustiva) – EFV
600mg QD
Empty stomach (or low-fat snack)
At bedtime
rilpivirine (Edurant) – RPV
25 mg QD
With at least 400 kcalories!
Initial treatment for HAART (backbone)? not drugs list
Recommended Initial Regimens for Most People with HIV:
2 NRTIs + 1 INSTI (“Backbone”)
5 Recommended Initial Regimens for Most People with HIV
Triumeq Tivicay + Truvada or Descovy Stribild Isentress + Truvada or Descovy Genvoya
Genvoya QD
elvitegravir, cobicistat, tenofovir AF, emtricitabine
Stribild QD
elvitegravir, cobicistat, tenofovir DF, emtricitabine
Triumeq QD
dolutegravir, abacavir, lamivudine
Follow-up for HIV patients
Follow-up in 2-4 weeks from starting HAART
- Adherence
- Side effects, tolerability, ADRs
- Transmission prevention
- Lab work
Routine follow-up every 3 months
Possibly every 6 months for patients with suppressed viral load and stable immunologic status
Efavirenz-Associated CNS Adverse Effects
Primary ADRs are related to CNS: Dizziness Confusion Impaired concentration Insomnia Abnormal dreams Irritability Depression
Taken QHS so as to sleep off CNS side effects
Empty stomach to reduce CNS side effects
High fat meal will significantly increase drug absorption and therefore increase side effects
Alcohol can potentiate CNS side effects
Genotypic Resistance Testing
Mutations within genes that code for proteins (enzymes) that are target of antiretroviral drugs
Valid ONLY for meds being given at the time of test
Resistant strains become “minority species” when drug pressure removed
Ideally test while ON medication
Archived resistance
Ritonavir (Norvir®, RTV)
The “Booster”
Boosting dose: 100 mg with PI with food
MANY drug interactions
Hepatotoxicity
Lipid abnormalities:
Elevated triglycerides and LDL
Monitor frequently
Pre-existing abnormality may not be a reason to avoid
Metabolic Complications of HAART
Associated with long-term antiretroviral use: Lipid abnormalities Lipodystrophy Hyperglycemia Decreased bone mineral density
Drug Interaction (Ex: lipid-lowering agent)
Ritoravir - Rosuvastatin and Atorvastatin
Simvastatin level increase significantly with PI use
Pneumocystis jiroveci pneumonia or Pneumocystis carinii pneumonia (PCP)
Gradual onset
Fever (Temp >38.1°)
Tachypnea
Chest exam may be normal (50%) if ↓air movement
Ronchi
Crackles
Radiologic manifestations differ from CAP or HAP
Toxoplasmosis and 3 clinical syndrome associate
Parasite: Toxoplasma gondii
Encephalitis/cerebral abscess
Headache
Fever
Mental status changes
Pneumonitis
Fever
Dyspnea
Cough
Chorioretinitis
Eye pain
Decreased visual acuity
Mycobacterium avium complex (MAC)
Disseminated Infection Fever Night sweats Abdominal pain Diarrhea Weight loss Elevated alkaline phosphase, LDH
Localized infection
Lymphadenopathy
Fever
Treatment for PCP for HIV patient
Bactrim DS QD or Dapsone 100mg QD
G6PD Deficiency
Treatment for Toxoplasmosis for HIV patient
Bactrim DS QD
Treatment for MAC for HIV patient
Azithromycin 1200mg Qweek
Opportunistic Infections in the HIV-Immunocompromised Host
PCP
MAC
Toxoplasmosis
Oral (thrush), oropharyngeal, & vaginal candidiasis
Disseminated infection:
Cryptococcal meningitis
Histoplasmosis
Blastomycosis
Cervical Abnormality in HIV patients
Increased risk of invasive cervical cancer
Screening
PAP testing Q 6 months during first year of diagnosis
PAP testing yearly if stable
PAP testing Q 6 months if CD4 <200
Menstruation and birth control in HIV patient
Earlier onset of menopause
Osteoporosis increase
Heart disease increase
Interruption in menstrual cycle
Hormone production
Oral contraceptives
Interaction with ethinyl estradiol; PI may decrease EE
Depo-Provera OK
TAF, TFV and TDF
TAF is an oral prodrug of tenofovir
TAF converted to TFV, and then to TFV-diphosphate intracellularly
TFV: nephrotoxic
TDF: readily converts to TFV in plasma after absorption
TAF remains stable in plasma resulting in lower plasma and higher intracellular concentrations
TAF MOA in ppt
Hepatitis C in HIV patients
HIV increases HCV replication and progression
Hepatotoxicity & antiretrovirals
Test for HCV initially and Q year
HCV viral load & LFTs to monitor progression in patients that are co-infected
Rilpivirine (in Complera®) & Acid-Reducing Agents
Antacids
Give antacid at least 2 hours before or at least 4 hours after RPV
H2RAs
Give H2RA at least 12 hours before or at least 4 hours after RPV
PPIs
CONTRAINDICATED: Do no co-administer
Primary prophylaxis for PCP for HIV patients
Must confirm G6PD Deficiency
If G6PD deficient:
THEN
Atovaquone suspension 1500mg QD
If G6DP is not deficient:
THEN
Dapsone 100mg QD (or 50mg BID)
Primary Prophylaxis for Toxoplasmosis for HIV patient
Dapsone alone does not cover Toxo
Dapsone 50mg QD + pyrimethamine 50mg Q week + leucovorin 25mg PO weekly
OR
Dapsone 200mg + pyrimethamine 75mg + leucovorin 25mg PO Q week
OR
Atovaquone 1500mg PO QD
Atazanavir (Reyataz) & ARAs
Antacids
Give ATV at least 2 hours before or 1 hour after antacids
H2RAs
Do not exceed famotidine 40mg BID in naïve pts
Give ATV 300mg + RTV 100mg simultaneously with and/or ≥ 10 hours after H2RA
PPIs
Do not exceed omeprazole 20mg QD in naïve pts
Should be given at least 12 hours before ATV/r
FYI: Precautions for Atazanavir
Transient hyperbilirubinemia Increase in indirect (unconjugated) bilirubin (avg: 0.3-0.5 mg/dL) Reversible upon discontinuation Inhibition of UDP glucuronyl transferase Liver unable to conjugate Scleral icterus Jaundice Typically resolves within 2 months
Nephrolithiasis and cholelithiasis have been reported
Consider temporary interruption or discontinuation
Hydration
Possible PR interval prolongation
FYI: Precautions for Darunavir
Has a sulfa moiety Use in caution in patients with a known sulfonamide allergy NOT a contraindication for use Drug-induced hepatitis Monitor LFTs before and during therapy Skin reactions Stevens-Johnson Syndrome Toxic Epidermal Necrolysis Discontinue use if severe reaction develops
Cobicistat precautions
Cobicistat is a pharmacokinetic booster with NO antiretroviral activity
It is a potent CYP3A4 inhibitor
Inhibits renal tubular secretion of creatinine
SCr will return to baseline after cobicistat discontinuation
DO NOT initiate COBI if Est CrCl < 70 mg/dL
DISCONTINUE COBI if Est CrCl < 50 mg/dL
Separate STRIBILD and antacids by 2 hours (due to elvitegravir)
Tivicay® (dolutegravir) and Triumeq®
Tivicay (dolutegravir) may be taken with or without food
Tivicay should be taken 2 hours before or 6 hours after taking cation-dontaining antacids or laxatives, sucralfate, oral supplements containing iron or calcium, or buffered medications.
ALTERNATIVELY: Tivicay and supplements containing calcium or iron can be taken together with food.
CD4 at which to initiate prophylaxis for PCP
<200 cells/mm^3
CD4 at which to initiate prophylaxis for Toxoplasmosis
<100 cells/mm^3
CD4 at which to initiate prophylaxis MAC
<50 cells/mm^3
CD4 at which to discontinue prophylaxis for PCP
> 200 cells/mm^3 for 3 months or longer
CD4 at which to discontinue prophylaxis for Toxoplasmosis
> 200 cells/mm^3 for 3 months or longer
CD4 at which to discontinue prophylaxis for MAC
> 100 cells/mm^3 for 3 months or longer
Diarrhea and HIV antivirals
“Break-in” period
Almost all medications
Concern for dehydration, weight loss Calcium supplements (Tums)
Pharmacologic therapies
Loperamide (Immodium®)
Diphenoxylate/atropine (Lomotil®)
Tips for patients Eat foods high in soluble fiber (oatmeal, bananas, bread) Avoid milk products Avoid greasy foods Plenty of fluids
Patterson’s Diarrhea Treatment Plan
Tums (calcium carbonate) regular or extra-strength
Take 2 tablets every 6 hours as needed
(Skip Step 1 if you are taking Reyataz® (atazanavir) or Viracept® (nelfinavir))
IF THAT DOESN’T WORK add…
Fibercon (calcium polycarbophil)
Take 1 tablet twice daily
IF THAT DOESN’T WORK add…
Imodium A-D (loperamide 2mg)
Take 2 capsules (4mg) now, then 1 every 4-6 hours as needed
(16 mg/day max)
Antihypertensives & Protease Inhibitors
Verapamil, diltiazem
PIs increase drug levels, cautious use
->Increased antihypertensive effect
Peripherally acting CCBs okay to use
Amlodipine
How to handle a missed dose for HIV drugs
Once daily and Twice daily:
If you miss a dose by less than 6/12 hours, take your missed dose right away. Then take your next dose at your regularly scheduled time.
If you miss a dose by more than 6/12 hours, wait and then take the next dose at your regularly scheduled time.
Do not take two doses at the same time to make up for a missed dose.
FYI: HIV Resistance Differs By Drug Class
NNRTIs & NRTIs:
- Efavirenz and several NRTIs have low barrier for resistance
- K103N mutation: all it takes to render efavirenz and nevirapine useless
- M184V mutation: all it takes to render emtricitabine or lamivudine useless
- Cross resistance possible
Protease Inhibitors:
-Unboosted protease inhibitors have resistance similar to NNRTIs and NRTIs
-Boosted protease inhibitors have high degree of forgiveness1
-May take several major mutations to confer resistance
-May take combination of major and minor mutations to confer resistance
Selective non-adherence to ritonavir is common2
Abacavir (Ziagen®, ABC)
300mg BID or 600mg QD with or without food
Hypersensitivity Reaction Fever N/V Malaise Myalgia/arthralgia Rash
First 2 months of therapy, gradual worsening of symptoms with each dose –>Do NOT re-challenge, next reaction could be FATAL
HLA-B*5701 allele test
HIV Pre-Exposure Prophylaxis (PrEP)
A biomedical intervention to prevent HIV infection in HIV-negative people.
1 tablet of Truvada taken every day
Truvada approved for PrEP in 2012
PrEP guideline in ppt
Truvada Medication Information
Dosing: one tablet by mouth once daily
Contraindications: unknown or positive HIV-1 status, monotherapy for HIV-1 infection
Precautions: hepatitis B virus co-infection, lactic acidosis, autoimmune disorders, osteomalacia
Mechanism of action: blocks virus from establishing infection
Inhibition of HIV-1 reverse transcriptase
Pregnancy category: B
Safe in pregnant patients if benefit outweighs risk
Breast Feeding: Infant risk cannot be ruled out
Dietary modifications: none, take with or without food
Side Effects: upset stomach, headache, vomiting, loss of appetite
Initial lab work:
HIV test, CMP, Hepatitis B & C serology, STI screening
Routine monitoring every 3 months
Rapid HIV test (ELISA)
Antibodies can take 3 to 6 months to develop
Kidney function (BMP)
PrEP affordability in ppt
