1. HIV Pharmacology Update
Katherine Gruenberg, PharmD, BCPS
PGY2 Pharmacy Resident, Infectious Diseases/Education
University of California, San Francisco School of Pharmacy

2. Session Outline New HIV single tablet regimens
Selected pipeline medications
Resource overview
Questions

3. Single Tablet Regimens

4. Single Tablet Regimens
First line:
Alternatives:
Brand Name
Generic
Genvoya®
elvitegravir/ cobicistat/ tenofovir alafenamide/emtricitabine
Stribild®
elvitegravir/ cobicistat/ tenofovir disoproxil fumarate/ emtricitabine
Triumeq®
dolutegravir/ abacavir/ lamivudine
Complera only recommended if HIV VL < 100k and CD4 > 200
Brand Name
Generic
Atripla®
efavirenz/ tenofovir disoproxil fumarate/emtricitabine
Complera®
rilpivirine/ tenofovir disoproxil fumarate/ emtricitabine
Odefsey®
rilpivirine/ tenofovir alafenamide/ emtricitabine

5. Tenofovir alafenamide (TAF) vs Tenofovir disoproxil fumarate (TDF)
Tenofovir alafenamide (TAF) is a newer formulation of tenofovir
Compared to TDF, TAF has:
(+) Less kidney damage
(+) Greater retention of bone mineral density
(+) Similar viral suppression
(-) Greater lipids
Many patients are being switched from TDF to TAF-containing regimens
TAF was compared to TDF in 2 randomized trials in ART-naïve patients. TAF was found to be non-inferior to TDF for HIV viral suppression. Patients treated with TAF were found to have smaller reductions in hip/spine bone mineral density and more favorable renal function (ie: less frequent discontinuation for renal adverse effects, and lower rate of decline in eGFR). However, patients treated with TAF were also found to have greater fasting lipid levels (LDL, HDL, and TG) compared to the TDF group

6. Stribild® Administration Take with food Common Adverse Effects Nausea
Diarrhea
Headache
Abnormal dreams
Monitoring
Serum creatinine
Drug interactions
Missed Doses
Take as soon as remembered, but do not double up
Administration: separate from antacids by at least 2 hours
Monitoring: Should not be used in Clcr < 50 (of note, cobicistat does cause small increase in Scr that doesn’t translate to true decrease in SCr so should expect bump up to 0.4 from baseline)
Contraindicated drug interactions: alfuzosin, rifampin, dihydroergotamine/ergotamine/methylergonovine, cisapride, st john’s wort, lovastatin, simvastatin, pimozide, sildenafil (PAH), triazolam, midazolam
- Caution should also be used is other drugs that are eliminated in similar manner in the kidney such as acyclovir, valacyclovir, valganciclovir
Stribild®[package insert]. Foster City, CA: Gilead Sciences, Inc.; 2012.

7. Genvoya® Administration Take with food Common Adverse Effects Nausea
Diarrhea
Headache
Monitoring
Serum creatinine
Total lipid panel
Drug interactions
Missed Doses
‘Do not miss a dose’
Administration: separate from antacids by at least 2 hours
Monitoring:
Should not be used in Clcr < 30
Contraindicated drug interactions: alfuzosin, CMZ/PHB/PHT, rifampin, dihydroergotamine/ergotamine/methylergonovine, cisapride, st john’s wort, lovastatin, simvastatin, pimozide, sildenafil (PAH), triazolam, midazolam
Additive risk of renal dysfunction: acyclovir, cidofovir, ganciclovir, valacyclovir, valganciclovir, aminoglycosides (e.g., gentamicin), and high-dose or multiple NSAIDs
Genvoya®[package insert]. Foster City, CA: Gilead Sciences, Inc.; 2015.

8. Triumeq® Administration* With/without food Adverse Effects Insomnia
Headache
Fatigue
Monitoring
Hepatic function
Drug interactions
Missed Doses
Take as soon as remembered; skip missed dose if ≤4 hours until next dose
Administration: separate 2 hours before or 6 hours after divalent cations- or take together with food
AE: very low incidence (ie < 5%)
Drug interactions: must increase DTG to 50mg BID if taken with efavirenz, fosamprenavir/r, tipranavir/r, or rifampin
-CI with dofetilide or moderate/severe hepatic impairment (ie: HCV patients)
-may need to limit metformin dose
Monitoring:
-Hepatic fxn primarily for HCV co-infection with moderate liver dysfunction or other RF for hepatic dysfxn
- Can inc scr without dec clcr (~0.14)
*Prior to starting Triumeq, a patient MUST be screened for the presence of a genetic allele: HLA-B*5701
Triumeq®[package insert]Research Triangle Park, NC: ViiV Healthcare, Inc.; 2014.

9. Pipeline Medications

10. Bictegravir Investigative 2nd generation integrase inhibitor
Co-formulated with tenofovir alafenamide and emtricitabine as single tablet regimen
Similar efficacy for viral suppression as dolutegravir
Adverse Effects:
Diarrhea
Nausea
Liver abnormalities
Slight decline in kidney function
Bictegravir is a possible pipeline option for patients who are treatment naïve without hepatitis co-infection. It was shown to be as efficacious as dolutegravir in combination with TAF/FTC and is co-formulated as a STR
The AE included: N/D/ reversible liver abnormalities and small declines in kidney funciton
This was a Phase 2 trial and there are phase 3 trials underway
Sax PE, et al. Lancet HIV Feb 14

11. Doravirine
Investigative non-nucleoside reverse transcriptase inhibitor
Co-formulated with tenofovir disoproxil fumarate and lamivudine as single tablet regimen
Efficacy similar to efavirenz and darunavir/ritonavir
Adverse Effects:
Diarrhea
Nausea
Headache
Abnormal dreams
(+) reduces fasting LDL and non-HDL
Doravirine is a NNRTI that also has activity against NNRTI resistant viruses (K103N, Y181C, G190A)
Has shown similar efficacy to EFV in addition to safety and tolerability
DRIVE-FORWARD: at 48wks, doravirine was non-inferior to DRV/r in achieving viral suppression
1. Molina, J-M, et al. Doravirine is non-inferior to darunavir/r in phase 3 treatment-naïve trial at week 48. Abstract presented at: CROI 2017; February 13-16, 2017; Seattle, WA
2. Gatel J, et al. Doravirine 100mg QD vs Efavirenz + TDF.FTC in ART-naïve HIV+ patients: Week 48 Results. Abstract presented at: CROI 2016; February 22-25, 2016; Boston, MA

12. Resources

13. Helpful Drug Resources
Patient Assistance Programs (PAP): Rxassist.org
Co-pay assistance programs: Rxassist.org/manufacturer webpage
ADAP
(p) (M-F, 8AM-5PM)
(f) OR
ADAP Pharmacy locator:
HIV warmline: (M-F, 9AM-8PM EST)
PEPline:
Perinatal HIV hotline:
PAP: for people without insurance (typically) and without federal drug assistance with Medicare or Medicaid
Co-pay assistance for those who HAVE private insurance – typically can get off drug manufacturer website
ADAP: you can call ADAP for questions about enrollment or eligibility
To submit applications you can either fax them or use their efax
From this website you can access the ADAP application forms
HIV provider warmline is a clinical consultation service that provides free advice on HIV management and prevention of transmission
HIV warmline

14. Questions?

15. Patient Case #1
ML is a 35 y/o male with newly diagnosed HIV who presents for a check-up. You ask him how he’s doing with his medications and he states: “I’m doing ok taking the Triumeq. I take it every day in the morning.”
ML’s other medications include:
Ferrous Sulfate 325mg PO TID with meals
Atorvastatin 40mg PO daily

16. Patient Case #1
What is the best counseling point for ML about his HIV regimen?
A. Do not take Triumeq with meals
B. Separate Triumeq from Atorvastatin
C. Take Triumeq with food
D. Take Triumeq together with ferrous sulfate and food

17. Patient Case #2
AM is a 21 y/o male who presents with newly diagnosed HIV and readiness to start antiretrovirals (ARV). He would like a tablet that he only has to take once daily starting today. The labs you have for AM are as follows: Viral load: 70,000 copies/mL CD4 count: 350 cells/mm3 Serum creatinine: 0.79 mg/dL Creatinine Clearance: 100 ml/min

18. Patient Case #2
Which first line ARV regimen would you recommend for AM to start today? A. Atripla® B. Genvoya® C. Darunavir/ritonavir + Truvada® D. Triumeq®
Atripla is not first line for tx naïve per guidelines
DRV/R + TDF/FTC is not STR
Need HLA for triumeq

19. Serum Creatinine (mg/dL) Creatinine Clearance (ml/min)
Patient Case #3
JY is a 67 y/o male with history of HIV (diagnosed in 1980) on Stribild® who presents for his annual checkup. He is very happy on his current regimen. His labs are as follows:
(5/12/17) HIV Viral load: undetectable
Atripla is not first line for tx naïve per guidelines
DRV/R + TDF/FTC is not STR
Need HLA for triumeq
Serum Creatinine (mg/dL)
Creatinine Clearance (ml/min)
1.54 (5/12/17) 46
1.01 (11/1/16) 70
0.90 (4/30/16) 78
0.89 (11/8/15)

20. Patient Case #3
Based on this patient’s labs, what would be the best adjustment to make to the patient’s regimen?
A. Change the patient to Genvoya®
B. Change the patient to Truvada® + Lopinavir/r
C. Dose adjust Stribild® to be given every other day
D. No changes need to be made
Atripla is not first line for tx naïve per guidelines
DRV/R + TDF/FTC is not STR
Need HLA for triumeq

21. Thank you!