1. 2018: HIV, HBV, and HCV Update
David Spach, MD Professor of Medicine, Division of Infectious Diseases University of Washington
Last Updated: August 10, 2018

2. 2018 HIV, HBV, and HCV Update
HIV
HBV
HCV

3. HIV Update

4. Total with Diagnosed HIV = 973,846
Updated page 94
Persons Living with Diagnosed HIV Infection in U.S. by Age, year end 2015
Total with Diagnosed HIV = 973,846
n = 519,652 (53.3%)
n = 454,684 (46.7%)
Source: CDC. HIV Surveillance Report, 2016;vol. 28: November 2017. 1

5. Estimated Incidence of HIV Infection in U.S. by Year, 2008-2013
Source: Hall HI, et al. JMIR Public Health Surveill. 2017;3:e8.

6. Estimated Incidence of HIV Infection in U.S. by Year, 2008-2013
Why?
Source: Hall HI, et al. JMIR Public Health Surveill. 2017;3:e8.

7. Estimated Incidence of HIV (NEW Infections) in U.S. by Age Group, 2015
Source: CDC. HIV Surveillance Supplemental Report. 2018;23(No. 1). March 2018 1

8. Preexposure Prophylaxis

9. What is PrEP?
Preexposure prophylaxis (PrEP): a prevention strategy in which an HIV-uninfected individual who is at high risk for HIV exposures takes a medication regularly to prevent HIV infection.

10. Preexposure Prophylaxis (PrEP)
Time
Preexposure Prophylaxis

11. Preexposure Prophylaxis (PrEP)
Time
Preexposure Prophylaxis

12. Preexposure Prophylaxis (PrEP)
HIV Exposure Events
Time
Preexposure Prophylaxis

13. Sexual Transmission of HIV
Genital Mucosal Surface
CD4 Cell

14. Oral Tenofovir DF-Emtricitabine (Truvada) as PrEP
Genital Mucosal Surface
CD4 Cell
Dendritic Cell
Macrophage

15. Oral Tenofovir DF-Emtricitabine as Sexual PrEP Protection During HIV Exposure Event
Genital Mucosal Surface
Dendritic Cell
CD4 Cell
Macrophage

16. Tenofovir DF-Emtricitabine as Sexual PrEP for HIV Prevention Estimated Protection in Adherent Patients
Source: Marrazzo JM, et al. JAMA. 2014;312: 1

17. Summary of Clinical Eligibility for HIV PrEP
Considered to be at “substantial risk” of HIV infection
Documented negative HIV test before prescribing PrEP
No symptoms of acute HIV infection
Normal renal function
Documented hepatitis B viral immune status
Able to adhere to a daily medication
Able to adhere to follow-up visits (at least every 3 months)
Source: US Public Health Service. Clinical practice guidelines for PrEP. May 2014.

18. 2014 CDC PrEP Guidelines: Summary of Recommendations for PrEP Prescribing
A. Determine Eligibility
Substantial ongoing risk for HIV
Able to take a pill every day and return every 3 months
Screen for HIV and consider need for HIV RNA (viral load)
Check hepatitis B antibody panel and renal function
B. Prescribe PrEP
Tenofovir DF-Emtricitabine (Truvada) 1 tab PO daily
Provice no more than 90 days of medication at a time
Emphasize importance of adherence
Source: US Public Health Service. Clinical practice guidelines for PrEP. May 2014.

19. 2014 CDC PrEP Guidelines: Summary of Recommendations for PrEP Prescribing
C. Continue Counseling
Continue risk-reduction counseling and other preventive measures (condoms, clean needles, etc)
Remember PrEP is not a stand-alone strategy
D. Lab Monitoring
Every 3 months HIV test
Every 3-6 months STI screening
Renal function at 3 months, then at least every 6 months
Source: US Public Health Service. Clinical practice guidelines for PrEP. May 2014.

20. Summary of Recommended Laboratory Evaluation Baseline and Routine Monitoring for Patients taking PrEP
Recommended Laboratory Testing and Frequency for Patients Taking PrEP
Laboratory test
Baseline
At least every 3 months
At least every 6 months
Notes
HIV screening assay ✔
Consider need for HIV RNA PCR
HBV antibody panel and HCV antibody
Offer HBV vaccination if not immune
Serum creatinine
Avoid PrEP if eCrCl <60 mL/min
STI testing
3 months if symptomatic or MSM with high-risk
Pregnancy test for women*
Åbbreviations: eCrCl = estimated creatinine clearance; STI = sexually transmitted infections *The safety of PrEP in pregnancy has not been established
Source: US Public Health Service. Clinical practice guidelines for PrEP Update.

21. Antiretroviral Update

22. HHS Antiretroviral Therapy Guidelines: January 28, 2016 Initiating Therapy in Treatment-Naïve Patients
2017 HHS Recommendation for Initiating ART Therapy in Treatment-Naïve Patients
Antiretroviral Therapy is Recommended for:
All HIV-infected individuals, regardless of CD4 T lymphocyte cell count, to reduce the morbidity and mortality associated with HIV infection. AI
For HIV-infected individuals to prevent HIV transmission.
Source: HHS Antiretroviral Therapy Guidelines. January 28, AIDS Info

23. HHS Antiretroviral Therapy Guidelines Preferred Initial Antiretroviral Therapy
Backbone
Anchor Drug
2 Nucleoside RTIs +
Integrase Inhibitor

24. Biktarvy [bik-TAR-vee]
Bictegravir-Tenofovir Alafenamide-Emtricitabine (Biktarvy) Single-Tablet Regimen
Biktarvy [bik-TAR-vee]
Bictegravir-Tenofovir alafenamide-Emtricitabine
INSTI
NRTI
NRTI

25. Bictegravir-Tenofovir alafenamide-Emtricitabine (Biktarvy)
Single-Tablet Regimen Components Bictegravir: 50 mg Tenofovir alafenamide: 25 mg Emtricitabine: 200 mg
Dosing: 1 pill daily with or without food
With Renal or Hepatic Impairment
Do not initiate if estimated CrCl <30 mL/min
Do not initiate with severe hepatic impairment (Child-Pugh C)
Pregnancy: insufficient data
Common Adverse Events (≥5%)
Diarrhea (6%), nausea (5%), and headache (5%)

26. BIC-TAF-FTC vs. DTG + TAF-FTC as Initial Therapy GS-380-1490: Design
GS : Study Design
Background: Randomized, double-blind, active- controlled, phase 3 study evaluating the efficacy and safety of bictegravir-tenofovir alafenamide- emtricitabine versus dolutegravir plus tenofovir alafenamide-emtricitabine for treatment-naïve individuals
Inclusion Criteria - Age >18 - Antiretroviral-naïve (or ≤10 days of treatment) - HIV RNA ≥500 copies/mL - eGFR ≥30 mL/min
Regimens - Bictegravir-TAF-FTC (50/25/200 mg) - Dolutegravir (50 mg) + TAF-FTC (25/200 mg)
Bictegravir-TAF-FTC
(n = 320)
Dolutegravir + TAF-FTC
(n = 325)
Source: Sax PE, et al. Lancet. 2017;390:

27. BIC-TAF-FTC vs. DTG + TAF-FTC as Initial Therapy GS-380-1490: Results
Week 48 Virologic Response (Intention-to-Treat Analysis)
286/320
302/325
No participant discontinued due to lack of efficacy in either arm No treatment-emergent resistance to any study drug occurred
Source: Sax PE, et al. Lancet. 2017;390:

28. Darunavir-Cobicistat-Tenofovir alafenamide-Emtricitabine
Darunavir-Cobicistat-Tenofovir Alafenamide-Emtricitabine (Symtuza) Single-Tablet Regimen
Symtuza [sim toó zah]
Darunavir-Cobicistat-Tenofovir alafenamide-Emtricitabine PI
Booster
NRTI
NRTI
Source: Image courtesy of Janssen Therapeutics, Division of Janssen Products, LP

29. DRV-COBI-TAF-FTC vs DRV-COBI + TDF-FTC as Initial ART AMBER: Design
AMBER: Study Design
Background: Randomized, double-blind, active- controlled, international, phase 3 study evaluating the efficacy and safety of the single-tablet regimen DRV-COBI-TAF-FTC compared with DRV-COBI + TDF-FTC for treatment-naïve individuals
Inclusion Criteria (n=725) - Age > Antiretroviral-naïve - CD4 count >50 cells/mm3 - HIV RNA ≥ 1,000 copies/mL - eGFR ≥ 70 mL/min - Genotypic sensitivity to DRV, TDF, and FTC - No hepatitis B or C - Not pregnant - No AIDS-defining condition within 30 days
DRV-COBI-TAF-FTC + 2 placebo tabs
(n = 362) 1x 1x
DRV-COBI + TDF-FTC + placebo tab
(n = 363)
Source: Eron JJ, et al. AIDS. 2018;32:

30. DRV-COBI-TAF-FTC vs DRV-COBI + TDF-FTC as Initial ART AMBER: Results
Week 48: Virologic Response by FDA Snapshot Analysis, ITT
331/362
321/363
278/303
265/293
53/59
56/70
Source: Eron JJ, et al. AIDS. 2018;32:

31. Dolutegravir-Rilpivirine (Juluca)
[Jah-LOO-kah]
Dolutegravir-Rilpivirine
50 mg
25 mg
INSTI
NNRTI
Dose: 1 tablet once daily with a meal
Photograph courtesy of ViiV

32. Dolutegravir-Rilpivirine (Juluca) Indications for Use
Complete regimen to replace the current antiretroviral regimen in those who are virologically suppressed (HIV-1 RNA less than 50 copies per mL)
On a stable antiretroviral regimen for at least 6 months
No history of treatment failure and no known substitutions associated with resistance to dolutegravir or rilpivirine.

34. Hepatitis B

35. Reported Number of Acute Hepatitis B Cases United States, 2001–2016
Source: National Notifiable Diseases Surveillance System (NNDSS)

36. Hepatitis B Recombinant Adjuvanted Vaccine (HepB-CpG) (Heplisav-B)
FDA Approved: November 9, 2017
Novel immunostimulatory sequence adjuvant
Approved for persons ≥18 years of age
ACP recommended in February 2018
Dosing: 2 doses 1 month apart

37. Hepatitis B Vaccine Comparison in Phase 3 Trials Heplisav-B versus Engerix
Source: Eron JJ, et al. AIDS. 2018;32:

38. Hepatitis B Recombinant Adjuvanted Vaccine (HepB-CpG) (Heplisav-B): Future Questions
Enhanced role in adults with improved dosing schedule?
Role in HBV vaccine non-responders?
Role in immunocompromised patients?
Role in children as routine immunization?

39. Hepatitis C Update

40. Hepatitis C: Progression of Disease
Time
20-25 years
25-30 years
Normal Liver
Chronic Hepatitis
Cirrhosis
HCC ESLD Death
HCV Infection

41. Noninvasive Tests to Evaluate Hepatic Fibrosis

42. Why Evaluate for Hepatic Fibrosis
Timing of Treatment - May accelerate timings
Duration of Treatment - Impacts duration with some regimens
Monitoring for Hepatocellular Carcinoma - Long-term implications for monitoring

43. Evaluation of Hepatic Fibrosis
Liver Biopsy - May accelerate timings
Indirect Markers - Aspartate Aminotransferase-to-Platelet-Ratio Index (APRI) - FIB-4 - Fibrotest (Fibrosure)
Radiographic - Hepatic Ultrasound - Transient Elastography (Fibroscan) - Shear Wave Elastography

44. Hepatitis C Virus and Potential Progression of Liver Disease
Metavir Fibrosis F1 F0 F2 F3 F4

45. Aspartate Aminotransferase-to-Platelet Ratio Index APRI Score
AST Level
AST (Upper Limit of Normal)
APRI =
Platelet Count (109/L)
× 100

46. Castera Transient Elastography Cutoffs Correlating with Metavir Fibrosis
Source:

47. HCV Treatment

48. AASLD/IDSA Hepatitis C Guidance Recommendation for Initiating Treatment
“Treatment is recommended for all patients with chronic HCV infection, except those with a short life expectancy that cannot be remediated by HCV therapy, liver transplantation, or another directed therapy.”
“Patients with a short life expectancy owing to liver disease should be managed in consultation with an expert.”
Source: AASLD/IDSA Hepatitis C Guidance

49. Hepatitis C Virus Structural and Nonstructural Proteins
Hepatitis C Protein Targets for Direct Acting Antiviral Agents (DAAs)
NS3
NS4A
NS5A
NS5B
Serine Protease
Serine Protease Cofactors
RNA binding and assembly recognition complex
RNA-Dependent RNA Polymerase

50. Categories of Direct Acting Antiviral Agents
Hepatitis C Direct Acting Antiviral Agent (DAA) Categories
NS3/4A Protease Inhibitor
NS5A Inhibitor
NS5B Polymerase Inhibitor
NS3
NS4A
NS5A
NS5B
Serine Protease
Serine Protease Cofactors
RNA binding and assembly recognition complex
RNA-Dependent RNA Polymerase

51. HCV Direct Acting Agents (DAAs)
NS3
NS4A
NS5A
NS5B
Protease Inhibitors
NS5A Inhibitors
Polymerase Inhibitors
“…previr”
“…asvir”
“…buvir”
Glecaprevir
Daclatasvir
Dasabuvir
Grazoprevir
Elbasvir
Sofosbuvir
Simeprevir
Ledipasvir
Voxilaprevir
Ombitasvir
Pibrentasvir
Velpatasvir

52. Hepatitis C Genotype 1a Costs of Different Regimens for Treatment of Genotype 1a
Estimated Cost* for Initial Recommend Treatment of Genotype 1a HCV
Regimen and Duration of Therapy^
Cost of Regimen*
Elbasvir-Grazoprevir for 12 weeks
$54,600
Elbasvir-Grazoprevir for 16 weeks
$72,800
Glecaprevir-Pibrentasvir for 8 weeks
$26,400
Ledipasvir-Sofosbuvir for 12 weeks
$94,500
Ombitasvir-Paritaprevir-Ritonavir + Dasabuvir + Ribavirin for 12 weeks
$83,819
Sofosbuvir + Simeprevir for 12 weeks
$150,000
Sofosbuvir-Velpatasvir for 12 weeks
$74,760
Sofosbuvir + Daclatasvir x 12 weeks
$147,000
^Regimen and Duration of therapy for Initial treatment of patients with Genotype 1a without cirrhosis
*Cost of regimen estimated based on Wholesale Acquisition Cost (WAC)

53. Glecaprevir-Pibrentasvir
Approval Status: Approval by United States FDA on August 3, 2017
Indications and Usage - Treatment-naïve patients with HCV genotypes 1-6 in without cirrhosis and with compensated cirrhosis (Child-Pugh A) - HCV genotype 1 previously treated with a regimen containing an HCV NS5A inhibitor or an NS3/4A protease inhibitor, but not both
Class & Mechanism - Glecaprevir: HCV NS3/4A protease inhibitor - Pibrentasvir: HCV NS5A inhibitor
Doseage Form (Tablet): 100 mg Glecaprevir and 40 mg Pibrentasvir
Dosing: Three tablets orally once daily, with food (total daily dose of Glecaprevir (300 mg)-Pibrentasvir 120 mg)
Adverse Effects (AE): most common headache and fatigue
Source: Mavyret Prescribing Information. AbbVie., Inc.

54. Glecaprevir-Pibrentasvir Indications: Treatment-Naïve Patients
Glecaprevir-Pibrentasvir in HCV Treatment-Naïve Patients
HCV Genotype
Treatment Duration
No Cirrhosis
Compensated Cirrhosis (Child-Pugh Class A)
Genotype 1
8 weeks
12 weeks
Genotype 2
Genotype 3
Genotype 4
Genotype 5
Genotype 6
Source: Mavyret Prescribing Information. AbbVie.

55. HIV, HBV, HCV: Update 2018
Questions