1. Antiretroviral Updates: New Treatments for HIV
C. Ryan Tomlin, Pharm.D., BCPS, AAHIVP
Mercy Health Saint Mary’s
Grand Rapids, Michigan

2. Outline Newly Released Antiretroviral Medications
Isentress HD® (raltegravir)
Juluca® (dolutegravir/rilpivirine)
Biktarvy® (bictegravir/emtricitabine/tenofovir alafenamide)
Trogarzo® (Ibalizumab)
Updates To The DHHS Guidelines
Medications In The Pipeline
Darunavir-based single tablet regimen
Cabotegravir
Doravirine
Fostemsavir
Dolutegravir/Lamivudine

3. Once-Daily Raltegravir
Additional drug interactions with: antacids, calcium carbonate, rifampin, tipranavir, etravirine, strong CPY 3A4 inducers
One 400mg Tablet Twice Daily
Two 600mg Tablets Once Daily

4. Dolutegravir / Rilpivirine
“First”, two-medication regimen for HIV
Indicated for patients:
Virally suppressed on another HIV regimen for at least 6 months
No history of prior treatment failure
No known resistance to dolutegravir or rilpivirine

5. SWORD 1 and 2 Screening Phase INSTI, PI, or NNRTI + 2 NRTIs
Switched to dolutegravir / rilpivirine (n=513)
Continued baseline regimen (n=511)
HIV RNA <50 for
6 months
Day 1
Week 48
Median Age
Sex
Ethnicity
CDC classification
CD4 count
Baseline third agent
DTG/RPV
43 years
77% male
23% female
82% white
11% AIDS
11% <350 cells/mm3
54% NNRTI
26% PI
20% INSTI
Baseline ART
79% male
21% female
78% white
10% <350
cells/mm3
27% PI
19% INSTI
Llibre JM, et al. Phase III SWORD 1&2. Program and abstracts of the 2017 Conference on Retroviruses and Opportunistic Infections; February 13-16, 2017; Seattle, Washington. Abstract 44LB.

6. (One patient developed a K101E at 36 weeks)
SWORD 1 and 2 Results
DTG/RPV
Baseline ART
Rate of viral failure
(HIV-1 ≥50 copies/mL)
<1% (3)
1% (6)
Treatment-emergent INSTI mutations with decreased susceptibility
Treatment-emergent NNRTI mutations with decreased susceptibility
(One patient developed a K101E at 36 weeks)

7. Same Medications / New Package
Must be taken with a meal
Based on the rilpivirine component
Adverse effects
Rash, Depressive Symptoms, Diarrhea, Headache
Common drug interactions
Significant CYP3A4 inducers or inhibitors
Acid suppressants
Polyvalent cations

8. Bictegravir Newest in the class of integrase inhibitors
Available as a fixed dose combo with tenofovir alafenamide and emtricitabine
Studied in both treatment naïve and treatment experienced patients

9. Bictegravir Treatment Naïve Studies
Study 1489
Study 1490
Treatment Naïve Adults with HIV VL ≥ 500 and GFR ≥ 50
Abacavir / Lamivudine / Dolutegravir
Tenofovir alafenamide / Emtricitabine / Bictegravir
Day 1
Week 48
Treatment Naïve Adults with HIV VL ≥ 500 and GFR ≥ 30
Tenofovir alafenamide / Emtricitabine + Dolutegravir
Tenofovir alafenamide / Emtricitabine / Bictegravir
Gallant J,, et al. Lancet. 2017;390(10107):
Sax PE,, et al. Lancet. 2017;390(10107):
Day 1
Week 48

10. Bictegravir Treatment Naïve Results
Study 1489 – TAF/FTC/BIC vs ABC/3TC/DTG
Study 1490 – TAF/FTC/BIC vs TAF/FTC, DTG
Gallant J, Lazzarin A, Mills A, et al. Lancet. 2017;390(10107):
Sax PE, Pozniak A, Montes ML, et al. Lancet. 2017;390(10107):

11. Bictegravir Switch Studies
Study 1844
Study 1878
Patients currently on ABC/3TC/DTG with HIV VL <50 and GFR ≥ 50
Abacavir / Lamivudine / Dolutegravir
Tenofovir alafenamide / Emtricitabine / Bictegravir
Day 1
Week 48
Patients currently on ABC/3TC or TDF/FTC with ATV or DRV with HIV VL <50 and GFR ≥ 50
Stayed on baseline PI regimen
Tenofovir alafenamide / Emtricitabine / Bictegravir
Daar E, et al. ID Week Conference, San Diego, Oct Abstract LB-4
Day 1
Week 48

12. Bictegravir Switch Results
Study 1844
Study 1878
Daar E, et al. ID Week Conference, San Diego, Oct Abstract LB-4

13. In Vitro Bictegravir Resistance
Tsiang M, Jones GS, Goldsmith J, et al. Antimicrob Agents Chemother :

14. Bictegravir Administration
Once daily with or without food
Not recommended in patients with estimated creatinine clearance < 30 mL/min
Common adverse effects:
Nausea
Diarrhea
Headache

15. Bictegravir Interactions
Strong inducers of both CPY3A and UGT1A1
Carbamazepine, Oxcarbazepine, Phenobarbital, Phenytoin
Rifabutin, Rifampin, Rifapentine
St. John’s Wort
Metformin
Dofetilide

16. Bictegravir and Polyvalent Cations
Antacids containing Al/Mg or Calcium: BIKTARVY can be taken under fasting conditions 2 hours before antacids containing Al/Mg or calcium.
Routine administration of BIKTARVY simultaneously with, or 2 hours after, antacids containing Al/Mg or calcium is not recommended.
Supplements containing Calcium or Iron: BIKTARVY and supplements containing calcium or iron can be taken together with food.
Routine administration of BIKTARVY under fasting conditions simultaneously with, or 2 hours after, supplements containing calcium or iron is not recommended.

17. Ibalizumab CD4-directed post attachment inhibitor
Indicated for patients with heavy multidrug resistance failing their current therapy
Given as an IV infusion every 14 days

18. Changes In Medication Recommendations
Most recently updated 3/27/18
Initiation of ART
Other Regimens
Alternative Regimens
Recommended Regimens
Recommended For Most People With HIV
Recommended In Certain Clinical Situations
Panel on Antiretroviral Guidelines for Adults and Adolescents. Guidelines for the Use of Antiretroviral Agents in Adults and
Adolescents Living with HIV. Department of Health and Human Services

19. First Line Regimens For Most People
Tenofovir
Emtricitabine
Elvitegravir
Cobicistat
NRTI
NRTI
Integrase Inhibitor
Booster
Tenofovir
Emtricitabine
Raltegravir
NRTI
NRTI
Integrase Inhibitor
Tenofovir
Emtricitabine
Dolutegravir
NRTI
NRTI
Integrase Inhibitor
Tenofovir
Emtricitabine
Bictegravir
NRTI
NRTI
Integrase Inhibitor
Abacavir
Lamivudine
Dolutegravir
NRTI
NRTI
Integrase Inhibitor

20. Why Integrase Inhibitors?
Faster Viral Load Suppression
Fewer Drug Interactions (save for elvitegravir)
Fewer Side Effects
INSTI PI
NNRTI
T-20

21. DHHS First Line Regimens
Genvoya / Stribild
Truvada/ Descovy + Tivicay
Truvada/ Descovy + Isentress
Triumeq
Biktarvy
# of Pills 1 2 3
Frequency
Daily
BID or Daily
Potential for Interactions
High
Low
Food Requirement
Yes No

22. Recommended In Certain Clinical Situations
Protease Inhibitor Regimens
NNRTI Regimens
Integrase Inhibitor Regimen
Tenofovir / Emtricitabine
Darunavir / booster Or Or
Abacavir / Lamivudine
Atazanavir / booster
Efavirenz
Tenofovir / Emtricitabine Or
Rilpivirine
Abacavir / Lamivudine
Raltegravir

23. HIV Medications In The Pipeline
Tenofovor AF/Emtricitabine/Darunavir/ Cobicistat
Cabotegravir
Doravirine
Fostemsavir
Dolutegravir/Lamivudine

24. Tenofovor AF/Emtricitabine/ Darunavir/Cobicistat
Tenofovir AF
Emtricitabine
Darunavir
Cobicistat ?

25. Symtuza®? Administration Side Effect Profile Drug Interactions
One pill, once-a-day, with food
Side Effect Profile
Headache, diarrhea, nausea, fatigue, rash
Drug Interactions
Similar to individual agents (3A4 boosting)
Role In Therapy
Patients requiring a very “durable” regimen

26. Cabotegravir Novel integrase inhibitor Potential indications:
HIV treatment when combined with rilpivirine
Pre-exposure prophylaxis
Formulations:
Long-acting intramuscular injection
Oral

27. LATTE-2 Trial Phase 2b, randomized, open label trial Inclusion:
Age ≥ 18
ART naïve
HIV VL ≥ 1,000
CD4 ≥ 200
CrCl ≥ 50
No major drug resistance
Margolis DA, et al. Lancet :

28. LATTE-2 Methods Cabotegravir 30mg PO Daily + Abacavir/ Lamivudine
Cabotegravir 400mg IM Q4Weeks +
Rilpivirine 600mg IM Q4Weeks (n=115)
Cabotegravir 600mg IM Q8Weeks +
Rilpivirine 900mg IM Q8Weeks (n=115)
Cabotegravir 30mg PO Daily + Abacavir / Lamivudine
(n=56)
Day 1
Week 20
Week 98 Post
Treatment Change
Margolis DA, et al. Lancet :

29. LATTE-2 Results 4 Week IM 8 Week IM Daily Oral Viral Response 87% 94%
84%
Viral Non-Response 0% 4% 2%
No Viral Data
13%
14%
Margolis DA, et al. Lancet :

30. Doravirine Novel NNRTI
Being studied in a single tablet regimen with tenofovir DF and lamivudine
Current clinical trials:
DRIVE-AHEAD: compared to efavirenz
DRIVE-FORWARD: compared to darunavir

31. DRIVE-FORWARD Trial
Patients with HIV viral load >1,000, ART naïve, and no resistance
Doravirine + 2 NRTIs + Boosted-Darunavir placebo
Boosted-Darunavir + 2 NRTIs + Doravirine placebo
Day 1
Week 48
Molina JM, et al. CROI. February 13-16, 2017, Seattle, Abstract 45LB

32. In Vitro Doravirine Resistance
Lai MT, et al. International Workshop on Antiviral Drug Resistance. 2014, Berlin, Germany

33. Fostemsavir gp 120 attachment inhibitor Potential indication:
Prevents binding to host CD4 receptors
Binds directly to the virus
Potential indication:
Highly treatment-experienced patients with multidrug-resistant HIV

34. BRIGHTE Study Randomized Cohort:
Treatment experienced patients failing current ART with only 1 or 2 active medications left
FTR + Failing ART
Open Label FTR + Optimized Background ART
Random 3:1
Placebo + Failing ART
Day 1
Day 8
Week 96
Non-Randomized Cohort:
Treatment experienced patients failing current ART with 0 active medications left
Open Label FTR + Optimized Background ART
Non-Random
M Kozal M, et al. 16th European AIDS Conference, October 25-27, Milan, Italy

35. BRIGHTE Results – Day 8
M Kozal M, et al. 16th European AIDS Conference, October 25-27, Milan, Italy

36. BRIGHTE Results – Viral Load Week 24
<400 77%
210
<200 71%
192
M Kozal M, et al. 16th European AIDS Conference, October 25-27, Milan, Italy

37. Dolutegravir / Lamivudine
Being studied as dual therapy in treatment naïve patients
Phase III Trials GEMINI 1 and 2 aim to compare dolutegravir/lamivudine to dolutegravir + emtricitabine/tenofovir DF
Not to be confused with the Gemini study of saquinavir

38. Antiretroviral Updates: New Treatments for HIV
C. Ryan Tomlin, Pharm.D., BCPS, AAHIVP
Mercy Health Saint Mary’s
Grand Rapids, Michigan