Use of Antiretroviral Agents in Adults and Adolescents
April 2015
AETC NCRC Slide Set
- Главная
- Разное
- Дизайн
- Бизнес и предпринимательство
- Аналитика
- Образование
- Развлечения
- Красота и здоровье
- Финансы
- Государство
- Путешествия
- Спорт
- Недвижимость
- Армия
- Графика
- Культурология
- Еда и кулинария
- Лингвистика
- Английский язык
- Астрономия
- Алгебра
- Биология
- География
- Детские презентации
- Информатика
- История
- Литература
- Маркетинг
- Математика
- Медицина
- Менеджмент
- Музыка
- МХК
- Немецкий язык
- ОБЖ
- Обществознание
- Окружающий мир
- Педагогика
- Русский язык
- Технология
- Физика
- Философия
- Химия
- Шаблоны, картинки для презентаций
- Экология
- Экономика
- Юриспруденция
Issues Affecting ART Success: Adherence, ARV Toxicity, Drug Interactions презентация
Содержание
- 1. Issues Affecting ART Success: Adherence, ARV Toxicity, Drug Interactions
- 2. July 2016 www.aidsetc.org About This Presentation These
- 3. Initiation of Therapy: Contents Adherence ARV-associated adverse effects Drug interactions July 2016 www.aidsetc.org
- 4. Adherence Strict adherence to ART is key
- 5. Factors Associated with Adherence Failure Regimen complexity
- 6. Factors Associated with Adherence Success Regimen
- 7. Predictors of Inadequate Adherence Age, race,
- 8. Measurement of Adherence No gold standard HIV
- 9. Improving Adherence A continuum of ART support
- 10. Improving Adherence (2) Simplify regimen, dosing, and
- 11. Improving Adherence (3) Use educational aids including
- 12. ART-Associated Adverse Effects Adverse effects (AEs) are
- 13. ART-Associated Adverse Effects (2) Lactic acidosis/hepatic steatosis
- 14. Adverse Effects Important to anticipate and overcome
- 15. Adverse Effects: NRTIs All NRTIs: Lactic
- 16. Adverse Effects: NRTIs (2) Emtricitabine (FTC) Minimal
- 17. Adverse Effects: NRTIs (3) Abacavir (ABC) Hypersensitivity
- 18. Adverse Effects: NRTIs (4) Didanosine (ddI)
- 19. Adverse Effects: INSTIs All INSTIs: Rash, hypersensitivity
- 20. Adverse Effects: INSTIs Dolutegravir (DTG) Headache Insomnia
- 21. Adverse Effects: PIs All PIs: Hyperlipidemia
- 22. Adverse Effects: PIs (2) Atazanavir (ATV) Hyperbilirubinemia
- 23. Adverse Effects: PIs (3) Indinavir (IDV) Nephrolithiasis
- 24. Adverse Effects: PIs (4) Saquinavir (SQV) GI
- 25. Adverse Effects: Pharmacokinetic Boosters Ritonavir (RTV, /r)
- 26. Adverse Effects: NNRTIs All NNRTIs: Rash, including
- 27. Adverse Effects: NNRTIs (2) Efavirenz (EFV) Neuropsychiatric
- 28. Adverse Effects: NNRTIs (3) Nevirapine (NVP) Higher
- 29. Adverse Effects: CCR5 Antagonist Maraviroc (MVC) Drug-drug
- 30. Adverse Effects: Fusion Inhibitor Enfuvirtide (ENF, T-20)
- 31. ARV-Associated Adverse Effects: Lactic Acidosis/Hepatic Steatosis
- 32. ARV-Associated Adverse Effects: Hepatotoxicity Severity variable: usually
- 33. ARV-Associated Adverse Effects: Insulin Resistance, Diabetes Insulin
- 34. ARV-Associated Adverse Effects: Fat Maldistribution Lipoatrophy:
- 35. ARV-Associated Adverse Effects: Hyperlipidemia ↑
- 36. ARV-Associated Adverse Effects: Cardiovascular and Cerebrovascular Effects
- 37. ARV-Associated Adverse Effects: Bone Density Effects TDF:
- 38. ARV-Associated Adverse Effects: Rash Most common with
- 39. ARV-Associated Adverse Effects: Nephrotoxicity Renal insufficiency
- 40. Overlapping Toxicities Peripheral neuropathy ddI, d4T, ddC,
- 41. Drug Interactions with ARVs Certain ARVs, particularly
- 42. Drug Interactions with ARVs (2) Increases in
- 43. Drug Interactions with ARVs (3) All PIs
- 44. Drug Interactions with ARVs (4) NRTIs No
- 45. Drug Interactions with ARVs (5) INSTIs RAL:
- 46. Drug Interactions with ARVs (6) CCR5 antagonist
- 47. Drug Interactions with ARVs (7) Cobicistat CYP
- 48. Common Drug Interactions with ARVs The following
- 49. Common Drug Interactions with ARVs (2) The
- 50. ARV-ARV Interactions Require dosage modification or cautious
- 51. ARV-ARV Interactions (2) Interactions involving ARVs
- 52. Websites to Access the Guidelines http://www.aidsetc.org http://aidsinfo.nih.gov July 2016 www.aidsetc.org
- 53. July 2016 www.aidsetc.org About This Slide Set
July 2016 www.aidsetc.org About This Presentation These slides were developed using the April 2015 guidelines and updated in July 2016. The intended audience is clinicians involved in the care of patients
Слайд 2July 2016
www.aidsetc.org
About This Presentation
These slides were developed using the April 2015
guidelines and updated in July 2016. The intended audience is clinicians involved in the care of patients with HIV.
Because the field of HIV care is rapidly changing, users are cautioned that the information in this presentation may become out of date quickly.
It is intended that these slides be used as prepared, without changes in either content or attribution. Users are asked to honor this intent.
– AETC NCRC http://www.aidsetc.org
Because the field of HIV care is rapidly changing, users are cautioned that the information in this presentation may become out of date quickly.
It is intended that these slides be used as prepared, without changes in either content or attribution. Users are asked to honor this intent.
– AETC NCRC http://www.aidsetc.org
Слайд 3Initiation of Therapy: Contents
Adherence
ARV-associated adverse effects
Drug interactions
July 2016
www.aidsetc.org
Слайд 4Adherence
Strict adherence to ART is key to virologic suppression, lower rates
of resistance, better quality of life, improved survival, and decreased risk of HIV transmission
Adherence also encompasses engagement and retention in care
ART regimens have become much simpler for initial therapy, but suboptimal adherence is common
Important to assess readiness for ART prior to initiating therapy, and to assess adherence at each clinic visit
Adherence also encompasses engagement and retention in care
ART regimens have become much simpler for initial therapy, but suboptimal adherence is common
Important to assess readiness for ART prior to initiating therapy, and to assess adherence at each clinic visit
July 2016
www.aidsetc.org
Слайд 5Factors Associated with Adherence Failure
Regimen complexity and pill burden
Low literacy or
numeracy level
Younger age
Some challenges of older age (eg, polypharmacy, vision loss, cognitive impairment)
Nondisclosure of HIV status
Stigma
Younger age
Some challenges of older age (eg, polypharmacy, vision loss, cognitive impairment)
Nondisclosure of HIV status
Stigma
July 2016
www.aidsetc.org
Psychosocial stressors
Active drug use or alcoholism
Mental illness (especially depression)
Cognitive impairment
Lack of patient education
Medication adverse effects
Treatment fatigue
Cost and insurance coverage issues
Слайд 6Factors Associated with Adherence Success
Regimen simplicity, once-daily dosing
Low pill burden
Good
tolerability
Older age
Multidisciplinary care (eg, with case managers, social workers, pharmacists, psychiatric care providers)
Directly observed therapy
Older age
Multidisciplinary care (eg, with case managers, social workers, pharmacists, psychiatric care providers)
Directly observed therapy
July 2016
www.aidsetc.org
Trusting patient-provider relationship
Use of motivational strategies
Слайд 7Predictors of Inadequate Adherence
Age, race, sex, educational level, socioeconomic status,
and a past history of alcoholism or drug use do NOT reliably predict suboptimal adherence
Higher socioeconomic status and education levels and lack of history of drug use do NOT reliably predict optimal adherence
Higher socioeconomic status and education levels and lack of history of drug use do NOT reliably predict optimal adherence
July 2016
www.aidsetc.org
Слайд 8Measurement of Adherence
No gold standard
HIV RNA suppression is one of the
most reliable indicators
Patient self-report may overestimate adherence, but is associated with viral load responses
Self-report of suboptimal adherence is strong indicator of suboptimal therapeutic response
Pharmacy records and pill counts can be helpful
Patient self-report may overestimate adherence, but is associated with viral load responses
Self-report of suboptimal adherence is strong indicator of suboptimal therapeutic response
Pharmacy records and pill counts can be helpful
July 2016
www.aidsetc.org
Слайд 9Improving Adherence
A continuum of ART support services is needed – team
may include providers from many disciplines
Strengthen early linkage to care and retention in care
Provide education on HIV disease, treatment, and prevention
Provide education on importance of adherence, and consequences of poor adherence
Establish readiness to start therapy
Individualize treatment, with patient involvement
Strengthen early linkage to care and retention in care
Provide education on HIV disease, treatment, and prevention
Provide education on importance of adherence, and consequences of poor adherence
Establish readiness to start therapy
Individualize treatment, with patient involvement
July 2016
www.aidsetc.org
Слайд 10Improving Adherence (2)
Simplify regimen, dosing, and food requirements
Review potential side effects
Anticipate
and treat side effects
Identify possible barriers to adherence and address these issues before starting ART
Use positive reinforcement
Systematically monitor treatment efficacy and retention in care
Identify possible barriers to adherence and address these issues before starting ART
Use positive reinforcement
Systematically monitor treatment efficacy and retention in care
July 2016
www.aidsetc.org
Слайд 11Improving Adherence (3)
Use educational aids including pictures, pillboxes, and calendars
Engage family,
friends
Utilize team approach with nurses, pharmacists, and peer counselors
Provide accessible, trusting health care team
Assess adherence at every clinic visit
Identify type and reasons for nonadherence
Utilize team approach with nurses, pharmacists, and peer counselors
Provide accessible, trusting health care team
Assess adherence at every clinic visit
Identify type and reasons for nonadherence
July 2016
www.aidsetc.org
Слайд 12ART-Associated Adverse Effects
Adverse effects (AEs) are one of the most common
reasons for nonadherence, and for switching or stopping ART
Newer ARV regimens generally result in fewer AEs
Longer-term complications of ARVs are not well studied
Risk of certain AEs may be higher in certain groups, eg, in women, those with comorbidities or on interacting medications
Important to consider possible AEs carefully in selecting ARVs for the individual patient
Newer ARV regimens generally result in fewer AEs
Longer-term complications of ARVs are not well studied
Risk of certain AEs may be higher in certain groups, eg, in women, those with comorbidities or on interacting medications
Important to consider possible AEs carefully in selecting ARVs for the individual patient
July 2016
www.aidsetc.org
Слайд 13ART-Associated Adverse Effects (2)
Lactic acidosis/hepatic steatosis
Hepatotoxicity
Insulin resistance, diabetes mellitus
Fat maldistribution
Hyperlipidemia
Cardiovascular and
cerebrovascular effects
Increased bleeding in hemophiliacs
Bone density effects
Rash
Increased bleeding in hemophiliacs
Bone density effects
Rash
July 2016
www.aidsetc.org
Слайд 14Adverse Effects
Important to anticipate and overcome ART toxicities in order to
achieve ART success over a lifetime
Consider potential adverse effects (AEs) when selecting ARV regimen; also consider patient’s comorbidities, other medications, and previous history of ARV intolerance
Consider potential adverse effects (AEs) when selecting ARV regimen; also consider patient’s comorbidities, other medications, and previous history of ARV intolerance
July 2016
www.aidsetc.org
Слайд 15Adverse Effects: NRTIs
All NRTIs:
Lactic acidosis and hepatic steatosis (highest incidence
with d4T, then ddI and ZDV, lower with TDF, ABC, 3TC, and FTC)
Lipodystrophy (higher incidence with d4T, ZDV)
Lipodystrophy (higher incidence with d4T, ZDV)
July 2016
www.aidsetc.org
Слайд 16Adverse Effects: NRTIs (2)
Emtricitabine (FTC)
Minimal toxicity
Hyperpigmentation
In HBV coinfection, exacerbation of
HBV if discontinued
Lamivudine (3TC)
Minimal toxicity
In HBV coinfection, exacerbation of HBV if discontinued
Lamivudine (3TC)
Minimal toxicity
In HBV coinfection, exacerbation of HBV if discontinued
July 2016
www.aidsetc.org
Слайд 17Adverse Effects: NRTIs (3)
Abacavir (ABC)
Hypersensitivity reaction*
Rash
Possible increased risk of MI
Tenofovir alafenamide
(TAF), tenofovir disoproxyl fumarate (TDF)
Renal impairment (less likely with TAF vs TDF)
Decrease in bone-mineral density (less likely with TAF vs TDF)
Headache, GI intolerance
Renal impairment (less likely with TAF vs TDF)
Decrease in bone-mineral density (less likely with TAF vs TDF)
Headache, GI intolerance
July 2016
www.aidsetc.org
* Screen for HLA-B*5701 before treatment with ABC; ABC should not be given to patients who test positive for HLA-B*5701.
Слайд 18Adverse Effects: NRTIs (4)
Didanosine (ddI)
GI intolerance
Peripheral neuropathy
Possible increased risk of
MI
Pancreatitis
Possible noncirrhotic portal hypertension
Stavudine (d4T)
Peripheral neuropathy
Lipoatrophy
Pancreatitis
Zidovudine (ZDV)
Headache
Bone marrow suppression
GI intolerance
Lipoatrophy
Pancreatitis
Possible noncirrhotic portal hypertension
Stavudine (d4T)
Peripheral neuropathy
Lipoatrophy
Pancreatitis
Zidovudine (ZDV)
Headache
Bone marrow suppression
GI intolerance
Lipoatrophy
July 2016
www.aidsetc.org
Слайд 19Adverse Effects: INSTIs
All INSTIs:
Rash, hypersensitivity reaction
Depression and suicidal ideation (rare; usually
in patients with preexistng psychiatric conditions)
July 2016
www.aidsetc.org
Слайд 20Adverse Effects: INSTIs
Dolutegravir (DTG)
Headache
Insomnia
Elvitegravir/cobicistat (EVG/COBI)
Decreased CrCl
Increased risk of TDF-related nephrotoxicity
Nausea, diarrhea
Raltegravir
(RAL)
Nausea
Headache
Diarrhea
CPK elevation, myopathy, rhabdomyolysis
Nausea
Headache
Diarrhea
CPK elevation, myopathy, rhabdomyolysis
July 2016
www.aidsetc.org
Слайд 21Adverse Effects: PIs
All PIs:
Hyperlipidemia
Lipodystrophy
Hepatotoxicity
GI intolerance
Possibility of increased bleeding
risk
for hemophiliacs
Drug-drug interactions
Drug-drug interactions
July 2016
www.aidsetc.org
Слайд 22Adverse Effects: PIs (2)
Atazanavir (ATV)
Hyperbilirubinemia
PR prolongation
Nephrolithiasis, cholelithiasis
Renal insufficiency
Darunavir (DRV)
Rash
Liver toxicity
Fosamprenavir (FPV)
GI
intolerance
Rash
Possible increased risk of MI
Rash
Possible increased risk of MI
July 2016
www.aidsetc.org
Слайд 23Adverse Effects: PIs (3)
Indinavir (IDV)
Nephrolithiasis
GI intolerance
Diabetes/insulin resistance
Lopinavir/ritonavir (LPV/r)
GI intolerance
Diabetes/insulin resistance
Possible increased
risk of MI
PR and QT prolongation
Nelfinavir (NFV)
Diarrhea
PR and QT prolongation
Nelfinavir (NFV)
Diarrhea
July 2016
www.aidsetc.org
Слайд 24Adverse Effects: PIs (4)
Saquinavir (SQV)
GI intolerance
PR and QT prolongation
Tipranavir (TPV)
GI intolerance
Rash
Hyperlipidemia
Liver
toxicity
Contraindicated if moderate-to-severe hepatic insufficiency
Cases of intracranial hemorrhage
Contraindicated if moderate-to-severe hepatic insufficiency
Cases of intracranial hemorrhage
July 2016
www.aidsetc.org
Слайд 25Adverse Effects: Pharmacokinetic Boosters
Ritonavir (RTV, /r)
GI intolerance
Hyperlipidemia, hyperglycemia
Hepatitis
Cobicistat (cobi, /c)
GI intolerance
Increase
in serum creatinine
July 2016
www.aidsetc.org
Слайд 26Adverse Effects: NNRTIs
All NNRTIs:
Rash, including Stevens-Johnson syndrome
Hepatotoxicity (especially NVP)
Drug-drug interactions
July 2016
www.aidsetc.org
Слайд 27Adverse Effects: NNRTIs (2)
Efavirenz (EFV)
Neuropsychiatric
Hyperlipidemia
Teratogenic in nonhuman primates + cases of
neural tube defects in human infants after 1st-trimester exposure
Etravirine (ETR)
Nausea
Etravirine (ETR)
Nausea
July 2016
www.aidsetc.org
Слайд 28Adverse Effects: NNRTIs (3)
Nevirapine (NVP)
Higher rate of rash
Hepatotoxicity (may be
severe and life-threatening;
risk higher in patients with higher CD4 counts at the time they start NVP, and in women)
Rilpivirine (RPV)
Depression
Insomnia
Headache
Rilpivirine (RPV)
Depression
Insomnia
Headache
July 2016
www.aidsetc.org
Слайд 29Adverse Effects: CCR5 Antagonist
Maraviroc (MVC)
Drug-drug interactions
Rash
Abdominal pain
Upper respiratory tract infections
Cough
Hepatotoxicity
Musculoskeletal symptoms
Orthostatic
hypotension
July 2016
www.aidsetc.org
Слайд 30Adverse Effects: Fusion Inhibitor
Enfuvirtide (ENF, T-20)
Injection-site reactions
HSR
Increased risk of bacterial
pneumonia
July 2016
www.aidsetc.org
Слайд 31ARV-Associated Adverse Effects: Lactic Acidosis/Hepatic Steatosis
Rare, but high mortality
Evidently
owing to mitochondrial toxicity
Associated with NRTIs (especially d4T, ddI, ZDV)
More common in women, pregnancy, obesity
Clinical presentation variable: have high index of suspicion
Lactate >2-5 mmol/dL plus symptoms
Treatment: discontinue ARVs, supportive care
Associated with NRTIs (especially d4T, ddI, ZDV)
More common in women, pregnancy, obesity
Clinical presentation variable: have high index of suspicion
Lactate >2-5 mmol/dL plus symptoms
Treatment: discontinue ARVs, supportive care
July 2016
www.aidsetc.org
Слайд 32ARV-Associated Adverse Effects: Hepatotoxicity
Severity variable: usually asymptomatic, may resolve without treatment
interruption
May occur with any NNRTI or PI, most NRTIs, or MVC:
NVP: risk of severe hepatitis in first few months of use (monitor LFTs closely), increased risk in chronic hepatitis B and C, women, and high CD4 count at initiation of NVP (>250 cells/µL in women, >400 cells/µL in men)
PIs: especially TPV/r; increased risk in hepatitis B or C, ETOH, other hepatotoxins
NRTIs: steatosis (especially AZT, d4T, ddI)
ddI; noncirrhotic portal hypertension
May occur with any NNRTI or PI, most NRTIs, or MVC:
NVP: risk of severe hepatitis in first few months of use (monitor LFTs closely), increased risk in chronic hepatitis B and C, women, and high CD4 count at initiation of NVP (>250 cells/µL in women, >400 cells/µL in men)
PIs: especially TPV/r; increased risk in hepatitis B or C, ETOH, other hepatotoxins
NRTIs: steatosis (especially AZT, d4T, ddI)
ddI; noncirrhotic portal hypertension
July 2016
www.aidsetc.org
Слайд 33ARV-Associated Adverse Effects: Insulin Resistance, Diabetes
Insulin resistance, hyperglycemia, and diabetes associated
with ZDV, d4T, ddI, some PIs (IDV, LPV/r), especially with chronic use
Mechanism not well understood
Insulin resistance, relative insulin deficiency
Screen regularly: fasting glucose
Mechanism not well understood
Insulin resistance, relative insulin deficiency
Screen regularly: fasting glucose
July 2016
www.aidsetc.org
Слайд 34ARV-Associated Adverse Effects: Fat Maldistribution
Lipoatrophy:
Peripheral fat wasting more associated with
NRTIs, especially thymidine analogues (d4T > ZDV, ddI > TDF, ABC, 3TC, FTC)
May be more likely when combined with EFV (compared with PI/r)
Lipohypertrophy
Central fat accumulation more associated with regimens containing PIs, EFV, RAL; causal relationship not established
May be associated with dyslipidemia, insulin resistance, lactic acidosis
Monitor closely; intervene early
Treatment: switching to other agents may slow or halt progression
May be more likely when combined with EFV (compared with PI/r)
Lipohypertrophy
Central fat accumulation more associated with regimens containing PIs, EFV, RAL; causal relationship not established
May be associated with dyslipidemia, insulin resistance, lactic acidosis
Monitor closely; intervene early
Treatment: switching to other agents may slow or halt progression
July 2016
www.aidsetc.org
Слайд 35ARV-Associated Adverse Effects: Hyperlipidemia
↑ total cholesterol, LDL, and triglycerides
Associated
with all RTV- or COBI-boosted PIs, EFV, NVP, d4T, ZDV, ABC, TAF > TDF, EVG/COBI/TDF/FTC
↑ HDL seen with EFV, RTV-boosted PIs, EVG/COBI
Concern for cardiovascular events, pancreatitis
Monitor regularly
Treatment: consider ARV switch; lipid-lowering agents (caution with PI + certain statins)
↑ HDL seen with EFV, RTV-boosted PIs, EVG/COBI
Concern for cardiovascular events, pancreatitis
Monitor regularly
Treatment: consider ARV switch; lipid-lowering agents (caution with PI + certain statins)
July 2016
www.aidsetc.org
Слайд 36ARV-Associated Adverse Effects: Cardiovascular and Cerebrovascular Effects
MI and CVA:
Risk of MI
and CVA associated with PIs in some cohort studies
Risk of MI with recent ABC and ddI use in some cohort studies (data are not consistent)
Seen especially in patients with traditional cardiovascular risk factors
Assess and manage cardiovascular risk factors
Consider ARVs with less risk of cardiovascular events, especially in patients at high risk of cardiovascular disease
Cardiac conduction abnormalities
PR prolongation with ATV/r, LPV/r, SQV/r
QT prolongation with RPV, SQV/r
Avoid if risk factors; baseline and monitoring ECG recommended
Risk of MI with recent ABC and ddI use in some cohort studies (data are not consistent)
Seen especially in patients with traditional cardiovascular risk factors
Assess and manage cardiovascular risk factors
Consider ARVs with less risk of cardiovascular events, especially in patients at high risk of cardiovascular disease
Cardiac conduction abnormalities
PR prolongation with ATV/r, LPV/r, SQV/r
QT prolongation with RPV, SQV/r
Avoid if risk factors; baseline and monitoring ECG recommended
July 2016
www.aidsetc.org
Слайд 37ARV-Associated Adverse Effects: Bone Density Effects
TDF: greater bone mineral density loss
than TAF, ZDV, d4T, or ABC
Decreases in BMD seen after initiation of any ART regimen
Other risk factors: low body weight, female, white or Asian ethnicity, older age, alcohol or tobacco use, hypogonadism, vitamin D deficiency, corticosteroid exposure
Consider assessment by DEXA
Management: consider alternative to TDF; calcium + vitamin D, bisphosphonate, weight-bearing exercise, hormone replacement
Decreases in BMD seen after initiation of any ART regimen
Other risk factors: low body weight, female, white or Asian ethnicity, older age, alcohol or tobacco use, hypogonadism, vitamin D deficiency, corticosteroid exposure
Consider assessment by DEXA
Management: consider alternative to TDF; calcium + vitamin D, bisphosphonate, weight-bearing exercise, hormone replacement
July 2016
www.aidsetc.org
Слайд 38ARV-Associated Adverse Effects: Rash
Most common with NNRTIs, especially NVP
Most cases mild
to moderate, occurring in first 6 weeks of therapy; occasionally serious (eg, Stevens-Johnson syndrome)
No benefit of prophylactic steroids or antihistamines (increased risk with steroids)
PIs: especially ATV, DRV, FPV, LPV/r, TPV
NRTIs: especially ABC (consider hypersensitivity syndrome)
FTC may cause hyperpigmentation
INSTI: RAL, EVG/COBI/TDF/FTC (uncommon)
CCR5 antagonist: MVC
No benefit of prophylactic steroids or antihistamines (increased risk with steroids)
PIs: especially ATV, DRV, FPV, LPV/r, TPV
NRTIs: especially ABC (consider hypersensitivity syndrome)
FTC may cause hyperpigmentation
INSTI: RAL, EVG/COBI/TDF/FTC (uncommon)
CCR5 antagonist: MVC
July 2016
www.aidsetc.org
Слайд 39ARV-Associated Adverse Effects: Nephrotoxicity
Renal insufficiency
TDF:
↑ Cr, proteinuria, glycosuria, hypophosphatemia, hypokalemia
Concurrent
RTV or COBI use may increase risk
TAF (vs TDF): less impact on renal biomarkers, lower rates of proteinuria
ATV, LPV/r: chronic kidney disease
IDV: ↑ Cr, pyuria, hydronephrosis or renal atrophy
COBI: nonpathologic ↓ in CrCl; also may increase risk of TDF-related nephrotoxicity
↑ risk in patients with renal disease, low CD4 count
Monitor Cr, other renal parameters
Management: stop the offending ARV + supportive care
Nephrolithiasis: IDV, ATV
TAF (vs TDF): less impact on renal biomarkers, lower rates of proteinuria
ATV, LPV/r: chronic kidney disease
IDV: ↑ Cr, pyuria, hydronephrosis or renal atrophy
COBI: nonpathologic ↓ in CrCl; also may increase risk of TDF-related nephrotoxicity
↑ risk in patients with renal disease, low CD4 count
Monitor Cr, other renal parameters
Management: stop the offending ARV + supportive care
Nephrolithiasis: IDV, ATV
July 2016
www.aidsetc.org
Слайд 40Overlapping Toxicities
Peripheral neuropathy
ddI, d4T, ddC, isoniazid
Bone marrow suppression
ZDV, dapsone, hydroxyurea, ribavirin,
TMP-SMZ
Hepatotoxicity
NVP, EFV, MVC, NRTIs, PIs, macrolides, isoniazid
Pancreatitis
ddI, RTV, d4T, TMP-SMZ, pentamidine
Hepatotoxicity
NVP, EFV, MVC, NRTIs, PIs, macrolides, isoniazid
Pancreatitis
ddI, RTV, d4T, TMP-SMZ, pentamidine
July 2016
www.aidsetc.org
Слайд 41Drug Interactions with ARVs
Certain ARVs, particularly PIs and NNRTIs, and the
PK booster COBI have significant drug interactions with other ARVs and with other medications
Interactions may be complex and difficult to predict
Coadministration of some ARVs with other ARV or non-ARV medications may require dosage adjustment, and some combinations may be contraindicated
Check for interactions before prescribing
Interactions may be complex and difficult to predict
Coadministration of some ARVs with other ARV or non-ARV medications may require dosage adjustment, and some combinations may be contraindicated
Check for interactions before prescribing
July 2016
www.aidsetc.org
Слайд 42Drug Interactions with ARVs (2)
Increases in serum drug levels caused by
inhibitors of metabolism may increase risk of medication toxicity, whereas decreases in drug levels caused by inducers of metabolism may cause treatment failure
Some drug interactions may be exploited, eg, low-dose RTV (a strong CYP3A4 inhibitor) may be used as a pharmacokinetic enhancer to increase concentrations and prolong the half-life of other PIs
Some drug interactions may be exploited, eg, low-dose RTV (a strong CYP3A4 inhibitor) may be used as a pharmacokinetic enhancer to increase concentrations and prolong the half-life of other PIs
July 2016
www.aidsetc.org
Слайд 43Drug Interactions with ARVs (3)
All PIs and NNRTIs are metabolized by
the hepatic CYP 450 system, particularly the CYP3A4
PIs
All PIs are CYP3A4 substrates, and their serum levels may be affected by CYP inducers or inhibitors
Some PIs also are inducers or inhibitors of other CYP isoenzymes or of P-glycoprotein (PGP) or other transporters
NNRTIs
Substrates of CYP3A4, can act as inducer (NVP) or mixed inducer and inhibitor (EFV)
ETR is substrate of 3A4, 2C9, and 2C19; inhibitor of 2C9 and 2C19
PIs
All PIs are CYP3A4 substrates, and their serum levels may be affected by CYP inducers or inhibitors
Some PIs also are inducers or inhibitors of other CYP isoenzymes or of P-glycoprotein (PGP) or other transporters
NNRTIs
Substrates of CYP3A4, can act as inducer (NVP) or mixed inducer and inhibitor (EFV)
ETR is substrate of 3A4, 2C9, and 2C19; inhibitor of 2C9 and 2C19
July 2016
www.aidsetc.org
Слайд 44Drug Interactions with ARVs (4)
NRTIs
No hepatic metabolism, but some NRTIs may
interact via other mechanisms (eg, decrease in ATV concentration if coadministered with TDF, proton pump inhibitors, H-2 receptor antagonists)
July 2016
www.aidsetc.org
Слайд 45Drug Interactions with ARVs (5)
INSTIs
RAL: eliminated by glucuronidation; inducers of UGT1A1
(eg, rifampin) can reduce RAL concentration
DTG: eliminated mostly by glucuronidation, minor contribution by CYP3A4; concentrations may be affected by inducers of UGT1A1 and CYP3A inhibitors or inducers; dosage adjustment necessary
EVG: requires boosting by COBI; many drug-drug interactions, owing to COBI
DTG: eliminated mostly by glucuronidation, minor contribution by CYP3A4; concentrations may be affected by inducers of UGT1A1 and CYP3A inhibitors or inducers; dosage adjustment necessary
EVG: requires boosting by COBI; many drug-drug interactions, owing to COBI
July 2016
www.aidsetc.org
Слайд 46Drug Interactions with ARVs (6)
CCR5 antagonist
MVC: substrate of CYP3A and PGP;
concentrations are significantly affected by CYP3A inhibitors or inducers; dosage adjustment necessary
Fusion inhibitor
ENF: no known significant drug interactions
Fusion inhibitor
ENF: no known significant drug interactions
July 2016
www.aidsetc.org
Слайд 47Drug Interactions with ARVs (7)
Cobicistat
CYP 3A4 an 2D6 inhibitor, no antiviral
activity, used as PK booster of other agents
Inhibits PGP-mediated transport
Many and complex drug-drug interactions
Inhibits PGP-mediated transport
Many and complex drug-drug interactions
July 2016
www.aidsetc.org
Слайд 48Common Drug Interactions with ARVs
The following require dosage modification or close
monitoring; some specific combinations should not be used:
Lipid-lowering agents
Antimycobacterials, especially rifampin*
Antifungals
Psychotropics – midazolam, triazolam
Ergot alkaloids
Antihistamines – astemizole
Anticonvulsants
Hepatitis C agents
Lipid-lowering agents
Antimycobacterials, especially rifampin*
Antifungals
Psychotropics – midazolam, triazolam
Ergot alkaloids
Antihistamines – astemizole
Anticonvulsants
Hepatitis C agents
July 2016
www.aidsetc.org
* Of NNRTIs and PIs, rifampin may be used only with full-dose RTV or with EFV.
Слайд 49Common Drug Interactions with ARVs (2)
The following require dosage modification or
close monitoring; some specific combinations should not be used:
Oral hormonal contraceptives, including emergency contraception (Plan B): may require alternative or second method
Methadone
Proton pump inhibitors, H2-receptor antagonists (eg, with ATV or RPV)
Aluminum-, magnesium-, or calcium-containing antacids (with INSTIs)
Erectile dysfunction agents
Herbs – St. John’s wort
Oral hormonal contraceptives, including emergency contraception (Plan B): may require alternative or second method
Methadone
Proton pump inhibitors, H2-receptor antagonists (eg, with ATV or RPV)
Aluminum-, magnesium-, or calcium-containing antacids (with INSTIs)
Erectile dysfunction agents
Herbs – St. John’s wort
July 2016
www.aidsetc.org
Слайд 50ARV-ARV Interactions
Require dosage modification or cautious use:
NNRTIs with PIs
NNRTIs with INSTIs
ATV
+ TDF
ddI + TDF
ddI + d4T
MVC + many PIs
MVC + EFV or ETR
ddI + TDF
ddI + d4T
MVC + many PIs
MVC + EFV or ETR
July 2016
www.aidsetc.org
Слайд 51ARV-ARV Interactions (2)
Interactions involving ARVs (or COBI) often require dosage
adjustment of the ARV and/or the interacting medication
Some combinations are contraindicated
Consider the possibility of interactions whenever adding a new medication
Consult with expert pharmacists or clinicians
Some combinations are contraindicated
Consider the possibility of interactions whenever adding a new medication
Consult with expert pharmacists or clinicians
July 2016
www.aidsetc.org
Слайд 52Websites to Access the Guidelines
http://www.aidsetc.org
http://aidsinfo.nih.gov
July 2016
www.aidsetc.org
Слайд 53July 2016
www.aidsetc.org
About This Slide Set
This presentation was prepared by Susa Coffey,
MD, for the AETC National Resource Center in April 2015 and updated in July 2016.
See the AETC National Coordinating Resource Center website for the most current version of this presentation:
http://www.aidsetc.org
See the AETC National Coordinating Resource Center website for the most current version of this presentation:
http://www.aidsetc.org
