Download IAS-USA at IAS 2012

Choosing the Initial
Antiretroviral Regimen
Paul A. Volberding, MD
Professor of Medicine
University of California San
Francisco
Presented
by PA Volberding, MD, IAS, July 25, 2012.
FINAL:
07-20-12
IAS–USA
Slide #2
Case 1 (1)
• Your patient is a 56 year old African American
man new to your care. He has known of his
infection for several years and has decided to
consider treatment for the first time.
• He is in good health but smokes cigarettes. He
is overweight but not obese. His total
cholesterol is 180 and his HDL is 30. His
systolic blood pressure is 142. His estimated
creatinine clearance is 75.
• His viral load is 65,000 copies/mL. His CD4
count is 420/µL.
Presented by PA Volberding, MD, IAS, July 25, 2012.
What Nucleoside “Backbone”
Would You Choose?
1.
2.
3.
4.
5.
Slide #3
TDF+FTC
ABC+3TC
ZDV+3TC
d4T+3TC
Other/ I’d start with a “nuc-sparing”
regimen
Presented by PA Volberding, MD, IAS, July 25, 2012.
Slide #4
Case 1 (2)
• Your patient is a 56 year old African American
man new to your care. He has known of his
infection for several years and has decided to
consider treatment for the first time.
• He is in good health but smokes cigarettes. He is
overweight but not obese. His total cholesterol is
180 and his HDL is 30. His systolic blood pressure
is 142. His estimated creatinine clearance is 65.
He is being treated for type 2 DM.
• His viral load is 65,000 copies/mL. His CD4 count
is 420/µL. He is HLA B5701 negative.
Presented by PA Volberding, MD, IAS, July 25, 2012.
What Nucleoside “Backbone”
Would You Choose?
1.
2.
3.
4.
5.
Slide #5
TDF+FTC
ABC+3TC
ZDV+3TC
d4T+3TC
Other/ I’d start with a “nuc-sparing”
regimen
Presented by PA Volberding, MD, IAS, July 25, 2012.
Slide #6
Case 1 (3)
• Your patient is a 56 year old African American man
new to your care. He has known of his infection for
several years and has decided to consider
treatment for the first time.
• He is in good health but smokes cigarettes. He is
overweight but not obese. His total cholesterol is
180 and his HDL is 30. His systolic blood pressure
is 142. His estimated creatinine clearance is 50. He
is being treated for type 2 DM.
• His viral load is 165,000 copies/mL. His CD4 count
is 420/µL. He is HLA B5701 negative.
Presented by PA Volberding, MD, IAS, July 25, 2012.
What Nucleoside “Backbone”
Would You Choose?
1.
2.
3.
4.
5.
Slide #7
TDF+FTC
ABC+3TC
ZDV+3TC
d4T+3TC
Other/ I’d start with a “nuc-sparing”
regimen
Presented by PA Volberding, MD, IAS, July 25, 2012.
Slide #8
2012 IAS-USA Guidelines
• NRTI+NNRTI:
• TDF+FTC+EFV
• ABC+3TC+EFV (If HLA-B 5701 negative, HIV RNA<100,000 copies)
• NRTI+PI/r
• TDF+FTC+DRN/r
• TDF+FTC+ATV/r
• ABC+3TC+ATV/r (If HLA-B 5701 negative, HIV RNA<100.000 copies)
• NRTI+InSTI
• TDF+FTC+RAL
Presented by PA Volberding, MD, IAS, July 25, 2012.
Have You Ever Chosen a nRTISparing Regimen as First-Line
Therapy?
1. Yes
2. No
Presented by PA Volberding, MD, IAS, July 25, 2012.
Slide #9
Slide #10
Case 2 (1)
• Your patient is about to start antiretroviral therapy for
the first time.
• He is a 36 year old with a CD4 count of 300/µL and a
viral load of 86,000 c/mL. He is healthy apart from his
HIV infection and is taking no other medications. His
cholesterol and renal function are normal. He has no
history of cardiovascular disease and is HCV and HBV
uninfected.
• Your patient is caught in the middle of the health care
economy and has to pay for his drug costs. He is not
wealthy and urges you to choose a good regimen that is
as inexpensive as possible.
Presented by PA Volberding, MD, IAS, July 25, 2012.
Slide #11
Which ARV Regimen Would Strike the
Best Balance Between Recommended
and Inexpensive?
1. ZDV+3TC (fdc)(generic)+nevirapine
2. TDF+FTC (fdc)+ saquinavir/ritonavir
3. ZDV (generic)+ddI (generic)+lopinavir/ritonavir
(fdc)
4. ABC+3TC (fdc)+efavirenz
5. ZDV (generic)+3TC (generic)+nevirapine XR
6. TDF+FTC+efavirenz (FDC)
Presented by PA Volberding, MD, IAS, July 25, 2012.
Slide #12
Which ARV Regimen Would Strike the Best Balance
Between Recommended and Inexpensive?
(All Monthly Average Wholesale Prices)
1. ZDV+3TC (fdc)(generic)+nevirapine
($931+$632=$1563)
2. TDF+FTC (fdc)+ saquinavir/ritonavir
($1392+$1089+$617=$3098)
3. ZDV (generic)+ddI (generic)+lopinavir/ritonavir (fdc)
($361+$369+$872=$1602)
4. ABC+3TC (fdc)+efavirenz ($1119+$690=$1809)
5. ZDV (generic)+3TC (generic)+nevirapine XR
$361+$430+$633=$1424)
6. TDF+FTC+efavirenz (FDC) ($2081)
Presented by PA Volberding, MD, IAS, July 25, 2012.
Slide #13
Which ARV Regimen Would Strike the
Best Balance Between Recommended
and Inexpensive?
(All Monthly Average Wholesale Prices)
1. ZDV+3TC (fdc)(generic)+nevirapine
($931+$632=$1563)
2. TDF+FTC (fdc)+ saquinavir/ritonavir
($1392+$1089+$617=$3098)
3. ZDV (generic)+ddI (generic)+lopinavir/ritonavir (fdc)
($361+$369+$872=$1602)
4. ABC+3TC (fdc)+efavirenz ($1119+$690=$1809)
5. ZDV (generic)+3TC (generic)+nevirapine XR
$361+$430+$633=$1424)
6. TDF+FTC+efavirenz (FDC) ($2081)
Presented by PA Volberding, MD, IAS, July 25, 2012.
Slide #14
What Do You Tend to Prescribe as an
Initial Regimen?
(Assume Viral Load <100,000)
1.
2.
3.
4.
5.
6.
TDF+FTC+efavirenz
ABC+3TC+efaviren
TDF+FTC+darunavir/ritonavir
TDF+FTC+atazanavir/ritonavir
ABC+3TC+atazanavir/ritonavir
TDF+FTC+raltegravir
Presented by PA Volberding, MD, IAS, July 25, 2012.
Slide #15
Case 3 (1)
• Your patient is a 36 year old HIV+ woman who was
diagnosed with post-traumatic stress following
sexual assault. She is anxious and depressed
despite therapy. She wants to start antiretrovirals
and feels she can be adherent but expresses a
strong reference for as few pills as possible, ideally
one per day. Her only medications are bupropion
(depression) and inhaled fluticasone (seasonal
allergies)
• Her viral load is 123,000 c/mL. Her CD4 count is
350 cells/µL.
Presented by PA Volberding, MD, IAS, July 25, 2012.
Slide #16
Given the Combination of Her HIV Status,
Co-morbid Conditions and Medications,
What Do You Recommend?
1.
2.
3.
4.
TDF+FTC+efavirenz (fdc)
TDF+FTC+rilpivarine (fdc)
TDF+FTC+elvitegravir/cobisistat (fdc)
I would not feel comfortable with any in
this situation
Presented by PA Volberding, MD, IAS, July 25, 2012.
Slide #17
Given the Combination of Her HIV Status,
Co-morbid Conditions and Medications,
What Do You Recommend?
1. TDF+FTC+efavirenz (fdc) (CNS risk with efavirenz,
childbearing potential)
2. TDF+FTC+rilpivarine (fdc) (Higher failure risk given
viral load over 100,000)
3. TDF+FTC+elvitegravir/cobisistat (fdc) (Drug
interaction potential between cobisistat and bupropion
and fluticasone)
4. I would not feel comfortable with any in this situation
(Bupropion is taken twice daily. Could she be
convinced to consider a twice daily ARV regimen?)
Presented by PA Volberding, MD, IAS, July 25, 2012.
Slide #18
Case 4
• A 29 year old woman hospitalized for pulmonary
TB at a program you support in Uganda is
simultaneously diagnosed with HIV infection. Her
viral load is 90,000 c/mL and her CD4 is 130
cells/µL.
• She has otherwise enjoyed good health. Her
baseline weight is 54 kg.
• Your treatment options for her TB are based on
rifampin.
Presented by PA Volberding, MD, IAS, July 25, 2012.
Which ARV Regimen is Best in
Her Case?
1.
2.
3.
4.
5.
Slide #19
d4T+3TC+nevirapine
d4T+3TC+efavirenz
TDF+FTC+efavirenz
Any two NRTI drugs+lopinavir/ritonavir
Other regimen
Presented by PA Volberding, MD, IAS, July 25, 2012.
Slide #20
2012 IAS-USA Guidelines
• “The recommended initial ART regimen in the setting
of rifampin based TB therapy is efavirenz plus NRTIs”
Presented by PA Volberding, MD, IAS, July 25, 2012.
Slide #21
Which Statement is Most Correct?
1. The combination of standard doses of rifampin and
efavirenz will reduce efavirenz concentration to levels
likely to lead to virologic failure
2. Given this patient’s weight, her efavirenz dose should
be increased to 800 mg daily
3. If efavirenz cannot be used, the best option is to obtain
rifabutin and use a boosted PI antiretroviral regimen
4. Rifabutin levels are increased by boosted PIs and a
reduced dose, 150 mg every two days, is indicated
Presented by PA Volberding, MD, IAS, July 25, 2012.
Slide #22
2012 IAS-USA Guidelines
1. “Recent studies..have not shown a clinically significant
effect of rifampin on efavirenz exposure”
2. “The current FDC with 600mg of efavirenz is associated
with good HIV and TB outcomes regardless of weight”
3. “If efavirenz cannot be used, the best option is to obtain
rifabutin and use a boosted PI antiretroviral regimen”
4. “Rifabutin 150mg/d is suggested when used with a PI/r
regimen and patients should be closely monitored”
Presented by PA Volberding, MD, IAS, July 25, 2012.