Choosing the Initial Antiretroviral Regimen

1. Choosing the Initial Antiretroviral Regimen Paul A. Volberding, MDProfessor of MedicineUniversity of California San Francisco FINAL: 07-20-12 Presented by PA Volberding, MD, IAS, July 25, 2012.

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.

3. What Nucleoside “Backbone” Would You Choose? • TDF+FTC • ABC+3TC • ZDV+3TC • d4T+3TC • Other/ I’d start with a “nuc-sparing” regimen

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.

5. What Nucleoside “Backbone” Would You Choose? • TDF+FTC • ABC+3TC • ZDV+3TC • d4T+3TC • Other/ I’d start with a “nuc-sparing” regimen

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.

7. What Nucleoside “Backbone” Would You Choose? • TDF+FTC • ABC+3TC • ZDV+3TC • d4T+3TC • Other/ I’d start with a “nuc-sparing” regimen

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

9. Have You Ever Chosen a nRTI-Sparing Regimen as First-Line Therapy? • Yes • No

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.

11. Which ARV Regimen Would Strike the Best Balance Between Recommended and Inexpensive? • ZDV+3TC (fdc)(generic)+nevirapine • TDF+FTC (fdc)+ saquinavir/ritonavir • ZDV (generic)+ddI (generic)+lopinavir/ritonavir (fdc) • ABC+3TC (fdc)+efavirenz • ZDV (generic)+3TC (generic)+nevirapine XR • TDF+FTC+efavirenz (FDC)

12. Which ARV Regimen Would Strike the Best Balance Between Recommended and Inexpensive?(All Monthly Average Wholesale Prices) • ZDV+3TC (fdc)(generic)+nevirapine ($931+$632=$1563) • TDF+FTC (fdc)+ saquinavir/ritonavir ($1392+$1089+$617=$3098) • ZDV (generic)+ddI (generic)+lopinavir/ritonavir (fdc) ($361+$369+$872=$1602) • ABC+3TC (fdc)+efavirenz ($1119+$690=$1809) • ZDV (generic)+3TC (generic)+nevirapine XR $361+$430+$633=$1424) • TDF+FTC+efavirenz (FDC) ($2081)

13. Which ARV Regimen Would Strike the Best Balance Between Recommended and Inexpensive?(All Monthly Average Wholesale Prices) • ZDV+3TC (fdc)(generic)+nevirapine ($931+$632=$1563) • TDF+FTC (fdc)+ saquinavir/ritonavir ($1392+$1089+$617=$3098) • ZDV (generic)+ddI (generic)+lopinavir/ritonavir (fdc) ($361+$369+$872=$1602) • ABC+3TC (fdc)+efavirenz ($1119+$690=$1809) • ZDV (generic)+3TC (generic)+nevirapine XR $361+$430+$633=$1424) • TDF+FTC+efavirenz (FDC) ($2081)

14. What Do You Tend to Prescribe as an Initial Regimen? (Assume Viral Load <100,000) • TDF+FTC+efavirenz • ABC+3TC+efaviren • TDF+FTC+darunavir/ritonavir • TDF+FTC+atazanavir/ritonavir • ABC+3TC+atazanavir/ritonavir • TDF+FTC+raltegravir

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.

16. Given the Combination of Her HIV Status, Co-morbid Conditions and Medications, What Do You Recommend? • TDF+FTC+efavirenz (fdc) • TDF+FTC+rilpivarine (fdc) • TDF+FTC+elvitegravir/cobisistat (fdc) • I would not feel comfortable with any in this situation

17. Given the Combination of Her HIV Status, Co-morbid Conditions and Medications, What Do You Recommend? • TDF+FTC+efavirenz (fdc) (CNS risk with efavirenz, childbearing potential) • TDF+FTC+rilpivarine (fdc) (Higher failure risk given viral load over 100,000) • TDF+FTC+elvitegravir/cobisistat (fdc) (Drug interaction potential between cobisistat and bupropion and fluticasone) • 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?)

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.

19. Which ARV Regimen is Best in Her Case? • d4T+3TC+nevirapine • d4T+3TC+efavirenz • TDF+FTC+efavirenz • Any two NRTI drugs+lopinavir/ritonavir • Other regimen

20. 2012 IAS-USA Guidelines • “The recommended initial ART regimen in the setting of rifampin based TB therapy is efavirenz plus NRTIs”

21. Which Statement is Most Correct? • The combination of standard doses of rifampin and efavirenz will reduce efavirenz concentration to levels likely to lead to virologic failure • Given this patient’s weight, her efavirenz dose should be increased to 800 mg daily • If efavirenz cannot be used, the best option is to obtain rifabutin and use a boosted PI antiretroviral regimen • Rifabutin levels are increased by boosted PIs and a reduced dose, 150 mg every two days, is indicated

22. 2012 IAS-USA Guidelines • “Recent studies..have not shown a clinically significant effect of rifampin on efavirenz exposure” • “The current FDC with 600mg of efavirenz is associated with good HIV and TB outcomes regardless of weight” • “If efavirenz cannot be used, the best option is to obtain rifabutin and use a boosted PI antiretroviral regimen” • “Rifabutin 150mg/d is suggested when used with a PI/r regimen and patients should be closely monitored”