1. 2017: HIV, STD, HBV, and HCV Update
David Spach, MD Professor of Medicine, Division of Infectious Diseases University of Washington
Last Updated: August 6, 2017

2. HIV, HBV, HCV: Update 2017
HIV
HBV
HCV
Questions

3. HIV Update

4. HIV Testing

5. Estimated HIV Prevalence in U.S.
? Number of Persons Living with HIV in US * *

6. Estimated HIV Prevalence in U.S.* *
Estimated 1,250,000 living with HIV in United States

7. Estimated Incidence of HIV Infection in U.S. by Year, 2006-2013
Source: Song R, et al. J Acquir Immune Defic Syndr. 2017;74:3-9. 1

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

9. 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.

10. Decreasing New HIV Infections
Reduce HIV undiagnosed fraction
Treatment as Prevention (TasP)
Preexposure Prophylaxis (PrEP)

11. Proportion with Undiagnosed HIV in U.S., by Year, 2007-2013
Source: CDC. HIV Surveillance Supplemental Report. 2016;21(No. 4):1-87. July 2016 1

12. Using Marks Model and 2008 CDC Data Estimating Impact of Knowledge of HIV Infection on Sexual Transmission of New HIV Infections
Using Marks Model & 2008 CDC Estimates of Awareness of HIV Status
Knowledge of HIV Infection
New HIV Infections
21%
48%
Unaware of HIV Infection
79%
52%
Aware of HIV Infection
Estimates Based on: Marks G, et al. AIDS. 2006;20: 1

13. HIV Prevention Trials Network (HPTN) Study 052
1,763 HIV Serodiscordant Couples (97% heterosexual) + - + - + - + -
n = 872
n = 853
n = 37
n = 1
Source: Cohen M, et al. N Engl J Med. 2011;36:

14. HIV Prevention Trials Network (HPTN) Study 052
550
Early Therapy CD cells/mm3
350
250
Deferred Therapy CD4 <250 cells/mm3 or AIDS-Related Event
Source: Cohen M, et al. N Engl J Med. 2011;36:

15. HIV Prevention Trials Network (HPTN) Study 052
96% Reduction
P < 0.001
Source: Cohen M, et al. N Engl J Med. 2011;36:

16. + - + - + - Heterosexual Couples MSM Couples n = 279 n = 269 n = 340
HIV Transmission with Condomless Sex if HIV-Infected with Suppressed HIV European PARTNER Study
Heterosexual Couples
MSM Couples + - + - + -
n = 279
n = 269
n = 340
767 HIV-serodiscordant couples in 14 European Countries
Partner with HIV taking ART and HIV RNA <200 copies/mL
Couples having condomless sex
Source: Rodger AJ, et al. JAMA 2016;316:

17. HIV Transmission with Condomless Sex if HIV-Infected with Suppressed HIV European PARTNER Study
Couples reported condomless sex meNo linked HIV transmissions during follow-up of 894 couple years
Uncertainty remains for upper limit of risk, particularly with receptive anal sex with ejaculation
Source: Rodger AJ, et al. JAMA 2016;316:

18. Preexposure Prophylaxis (PrEP)
Time
Preexposure Prophylaxis

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

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

21. Antiretroviral Update

22. CDC and Association of Public Health Laboratories Laboratory Testing for the Diagnosis of HIV Infection
HIV-1/2 Antigen/Antibody Immunoassay
(+)
(-)
Negative for HIV-1 and HIV-2 antibodies and p24 Ag
HIV-1/HIV-2 Ab Differentiation Immunoassay
HIV-1 (+) HIV-2 (-)
HIV-1 (-) HIV-2 (+)
HIV-1 (+) HIV-2 (+)
HIV-1 (-) or Indeterminate HIV-2 (-)
HIV-1 antibodies detected
HIV-2 antibodies detected
HIV antibodies detected
HIV-1 NAT
HIV-1 NAT (+)
HIV-1 NAT (-)
Acute HIV-1 infection
Negative for HIV-1
Source: Centers for Disease Control and Prevention. June 27, 2014.

23. CDC and Association of Public Health Laboratories Laboratory Testing for the Diagnosis of HIV Infection
HIV-1/2 Antigen/Antibody Immunoassay
HIV p24 Antigen
HIV Antibodies
(+)
(-)
Negative for HIV-1 and HIV-2 antibodies and p24 Ag
HIV-1/HIV-2 Ab Differentiation Immunoassay
HIV-1 (+) HIV-2 (-)
HIV-1 (-) HIV-2 (+)
HIV-1 (+) HIV-2 (+)
HIV-1 (-) or Indeterminate HIV-2 (-)
HIV-1 antibodies detected
HIV-2 antibodies detected
HIV antibodies detected
HIV-1 NAT
Detects HIV-1 p24 antigen and antibodies to HIV-1 and HIV-2
HIV-1 NAT (+)
HIV-1 NAT (-)
Acute HIV-1 infection
Negative for HIV-1
Source: Centers for Disease Control and Prevention. June 27, 2014.

24. CDC and Association of Public Health Laboratories Laboratory Testing for the Diagnosis of HIV Infection
HIV-1/2 Antigen/Antibody Immunoassay
(+)
(-)
Negative for HIV-1 and HIV-2 antibodies and p24 Ag
HIV-1/HIV-2 Ab Differentiation Immunoassay
HIV-1 (+) HIV-2 (-)
HIV-1 (-) HIV-2 (+)
HIV-1 (+) HIV-2 (+)
HIV-1 (-) or Indeterminate HIV-2 (-)
HIV-1 antibodies detected
HIV-2 antibodies detected
HIV antibodies detected
HIV-1 NAT
HIV-1 NAT (+)
HIV-1 NAT (-)
Acute HIV-1 infection
Negative for HIV-1
Source: Centers for Disease Control and Prevention. June 27, 2014.

25. Geenius HIV-1/HIV-2 Supplemental Assay

26. Geenius HIV-1/HIV-2 Supplemental Assay
Immunochromographic Assay: Detects HIV-1 and HIV-2 Antibodies
HIV-2 Bands
HIV-1 Bands
Control
gp36
gp140
p31
gp160
p24
gp41
Source: Fernández-McPhee C, et al. J Clin Virol. 2015;63:66-9.

27. Geenius HIV-1/HIV-2 Supplemental Assay Software Interpretation
Source: Geenius Product Information

28. Antiretroviral Update

29. 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

30. HHS Recommended Initial Antiretroviral Therapy
Backbone
Anchor Drug
Integrase Inhibitor
2 Nucleoside RTIs +
Protease Inhibitor (Boosted)

31. Hepatitis B

32. Hepatitis B Reactivation During HCV Treatment Reports
Reports of HBV reactivation in persons coinfected with HCV-HBV coninfection
Cases have involved active (HBsAg+) and resolved (HBsAg- and HBcAb+)
Some cases severe: fulminant hepatitis, liver failure, death
FDA warning October 4, 2016

33. Hepatitis B Reactivation During HCV Treatment AASLD/IDSA HCV Guideance: Recommendation
Test all patients for HBsAg, HBcAb, and HBsAb prior to treating HCV
Patients with active HBV should receive HBV therapy if indicated
If HBsAg positive and not receiving therapy, obtain HBV DNA levels at baseline and monitor during therapy
Note: some experts would treat HBV in all persons with HBsAg prior to starting HCV therapy, regardless of HBV DNA level

34. Hepatitis C Update

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

36. 2005 Forecast of HCV-Associated Deaths in U.S.
Number
Year
2010
Deaths
2014
2018
2022
2026
2030
2034
2038
2042
2046
2050
2054
2058
40,000
35,000
30,000
25,000
20,000
15,000
10,000
5,000
45,000
Source: Rein DR, et al. Dig Liver Dis. 2011:43:66-72.

37. Hepatitis C Virus Structural and Nonstructural Proteins
Hepatitis C Proteins C
NS4B
NS5A
NS2
NS3 E1
NS4A p7 E2
NS5B
Structural Proteins
Nonstructural (NS) Proteins
Cysteine Protease
Serine Protease Cofactors
RNA binding and assembly recognition complex
Vioporin
Serine Protease
RNA Helicase
Membranous Web Induction
RNA-Dependent RNA Polymerase

38. 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

39. 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

40. HCV Direct Acting Agents (DAAs)
NS3
NS4A
NS5A
NS5B
Protease Inhibitors
NS5A Inhibitors
Polymerase Inhibitors
Glecaprevir
Daclatasvir
Dasabuvir
Grazoprevir
Elbasvir
Sofosbuvir
Simeprevir
Ledipasvir
Voxilaprevir
Ombitasvir
Pibrentasvir
Velpatasvir

41. 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.

42. 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.

43. Glecaprevir/Pibrentasvir in Cirrhotic Genotype 1, 2, 4, 5, and 6 EXPEDITION-1: Results with 12-Week Treatment
145/146
89/90
31/31
16/16
2/2
7/7
SVR12 by intent-to-treat analysis. N=1 patient with GT1A experienced viral relapse at week 8 post-treatment; had Y93N detected at baseline & at time of failure.
Source: Forns X, et. al, EASL Abstract GS-006.

44. SVR12 (ITT analysis), Overall and by Genotype
Glecaprevir-Pibrentasvir in Non-Cirrhotic Genotype 4, 5 and 6 ENDURANCE-4: Results
SVR12 (ITT analysis), Overall and by Genotype
50/51
51/51
50/51
50/51
120/121
75/76
26/26
19/19
Source: Asselah T, et al. AASLD 2016, Abstract 114.

45. Glecaprevir-Pibrentasvir in Treatment-Naïve Non-Cirrhotic GT 3 ENDURANCE-3 Study: Results
ION-3: SVR 12 by Treatment Duration and Regimen (ITT Analysis)
222/233
111/115
149/157
12-Week Regimens
8-Week Regimen
GLE-PIB = glecaprevir-pibrentasvir; SOF = sofosbuvir; DCV = daclatasvir
ITT = Intent-to-treat
Source: Foster G, et al. EASL 2017, Abstract GS-007.

46. 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)

47. Sofosbuvir-Velpatasvir-Voxilaprevir Indications: Treatment-Experienced Only
Sofosbuvir-Velpatasvir-Voxilaprevir for Adults with Chronic HCV without Cirrhosis or with Compensated Cirrhosis (Child-Pugh A)
HCV Genotype
Patient Previously Treated With an HCV Regimen Containing:
Treatment Duration
1, 2, 3, 4, 5, or 6
An NS5A inhibitora
12 weeks
1a or 3
Sofosbuvir without an NS5A inhibitorb
aIn clinical trials, prior NS5A inhibitor experience included daclatasvir, elbasvir, ledipasvir, ombitasvir, or velpatasvir. bIn clinical trials, prior treatment experience included sofosbuvir with or without any of the following: peginterferon alfa/ribavirin, ribavirin, HCV NS3/4A protease inhibitor (boceprevir, simeprevir or telaprevir).
Source: Vosevi Prescribing Information, Gilead Sciences.

48. Sofosbuvir-Velpatasvir-
Sofosbuvir-Velpatasvir-Voxilaprevir in NS5A-Experienced GT 1-6 POLARIS-1: Study Design 12 24
Week
GT 1-6 with NS5A inhibitor experience*
n = 415
Sofosbuvir-Velpatasvir-
Voxilaprevir
N=263
SVR12
Placebo
N=152
SVR12
GT 1 patients randomized 2:1 ratio (active:placebo). Stratified by presence of cirrhosis (target ≥30%).
Genotypes 2-6 were assigned to active arm (and not randomized).
Placebo recipients were eligible for deferred treatment with sofosbuvir-velpatasvir-voxilaprevir
Drug Dosing Sofosbuvir-Velpatasvir-Voxilaprevir (400/100/100 mg): fixed dose combination; one pill once daily Placebo: one pill once daily
Source: Bourlière M, et al. N Engl J Med. 2017;376:

49. Sofosbuvir-Velpatasvir-Voxilaprevir in NS5A-Experienced GT 1-6 POLARIS-1: Prior NS5A Treatment
133/263
70/263
30/263
33/263
Source: Bourlière M, et al. N Engl J Med. 2017;376:

50. Sofosbuvir-Velpatasvir-Voxilaprevir in NS5A-Experienced GT 1-6 POLARIS-1: Results by Genotype
97/101
45/45
5/5
74/78
20/22
1/1
6/6
Source: Bourlière M, et al. N Engl J Med. 2017;376:

51. HIV, HBV, HCV: Update 2017
HIV
HBV
HCV
Questions