5/20/2015

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HIV/AIDS Review 2015

• What did you learn most?

• What are you going to do

with this information?

• What would be barriers to

implementation?

www.FutureMe.org

5/20/2015

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1)Improve the health of populations

2)Enhance the patient experience of care

3)Reduce the per capita cost of health care

4)Improve the work life of clinicians and staff

www.annfammed.org/content/12/6/573.full

HIV-Hepatitis Overview 2015

Danny Toub MD dannyt@srhealthcenters.org

April 25, 2015 North Coast AIDS ETC HIV/AIDS Review

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HIV/HCV Overview

• Epidemiology/Care Continuum

• Mortality/Social Determinants of Health

• Safety, Tolerability, Effectiveness, Price, and Simplicity (STEPS) of Antiviral Treatment

https://blog.aids.gov/2015/04/hiv-care-continuum-video-

updated.html

5/20/2015

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• The majority of persons currently living with HIV

infection in Sonoma County are white males.

• The number of newly diagnosed AIDS cases continues

to decline, primarily as a result of effective treatment.

• There are an average of 40 persons newly diagnosed

with HIV infection per year in Sonoma County.

Geography

Newly diagnosed persons

with HIV infection reside

throughout the county.

Guerneville (95446) has the

highest rate of recently

diagnosed cases, followed by

Southwest Santa Rosa

(95407).

Santa Rosa (N=27, 95407;

N=17, 95404) has the highest

number of new infections.

— -

*Zip code of residence

reported at time of diagnosis.

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A Portrait of Sonoma County

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Source: Ly KN, et al. Ann Intern Med. 2012:156:271-8.

Age-Adjusted Mortality Rates* from HBV, HCV, & HIV

United States, 1999-2007

*Mortality Rates = HBV, HCV, HIV listed as cause of death

Rate

per

100,0

00 P

Y

Year

HIV

1999 2000 2001 2002 2003 2004 2006 2007 2005

5

4

3

2

1

0

7

6

Hepatitis C

Hepatitis B

n = 15,106

http://attcnetwork.org/pdf/ATTC-HepC-Flyer-2.pdf

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Source: Holmberg SD, et al. N Engl J Med. 2013;368:1859-61.

Hepatitis C Cascade of Care in United States

3,200,000

Chronic HCV HCV Detected Referred to Care HCV Treated Achieved SVR

Nu

mb

er

of

Pe

rso

ns

(M

illi

on

s)

100%

50%

35%

9% 6%

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Forecasted 2010-2060 Annual HCV-Related Deaths in the United States

Persons with Chronic Hepatitis C and no Cirrhosis in 2005

Source: Rein DR, et al. Dig Liver Dis. 2011:43:66-72.

Nu

mb

er

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

0

45,000

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Santa Rosa Community Health Centers Deaths of HIV+ Patients 2010-2015

Santa Rosa Community Health Centers Deaths of HIV+ Patients 2010-2015

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Smoking has a bigger impact on the prognosis of HIV-positive patients than

HIV-related factors

Smoking doubles risk of death for patients taking HIV therapy

N=18,000 HIV+ pts Europe & North America who started HIV therapy between 1996 and 2008. Most patients (60%) were smokers.

All-cause mortality rate

-7.9 per 1000 person-years for smokers

-4.2 per 1000 person-years for non-smokers.

Helleberg M et al. Smoking and life expectancy among HIV-infected individuals on antiretroviral therapy in Europe and North America: the ART Cohort Collaboration. AIDS 28 (online edition). DOI: 10.1097/QAD.0000000000000540 (2014).

VACS Index Calculator http://vacs.med.yale.edu/IC

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ART Timeline for Approval

What to Start: Recommended Initial Combination Regimens for the

Antiretroviral-Naive Patient 4/8/15 DHHS Guidelines http://aidsinfo.nih.gov/guidelines/html/1/adult-

and-adolescent-treatment-guidelines/0

INTEGRASE STRAND TRANSFER INHIBITOR BASED REGIMENS FREQUENCY PILL #

Dolutegravir/Abacavir/Lamivudine Once daily 1

Dolutegravir + Tenofovir Disoproxil Fumarate (Tenofovir)/ Emtricitabine

Once daily 2

Elvitegravir/cobicistat/Tenofovir/Emtricitabine Once daily 1

Raltegravir + Tenofovir/Emtricitabine Twice daily 3

PROTEASE INHIBITOR BASED REGIMENS

Darunavir/ritonavir + Tenofovir/Emtricitabine Once daily 3

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Therapy for Hepatitis C

Projected SVR Rates with Multiple DAAs

6

16

34

42 39

55

70

90 95

0

20

40

60

80

100

IFN6m

IFN12m

IFN + RBV6m

IFN + RBV12m

PEG12m

PEG + RBV12m

PEG + RBV +PI 6-12m

PEG + RBV+Sofosbuvir

3m

Multiple DAAs

Su

sta

ined

Vir

olo

gic

Resp

on

se (

%)

Timeline

2011 2014 2015

What to Start: HCV Treatment Guidelines for Treatment naïve

patients with Genotype 1A www.HCVGuidelines.org (AASLD/IDSA) and

www.hepatitis.va.gov/HEPATITIS/provider/guidelines/index.asp#S2X (VA)

REGIMEN FREQUENCY LENGTH OF TX: non-cirrhotics

LENGTH OF TX: cirrhotics

Ledipasvir (90 mg)/Sofosbuvir (400 mg) Harvoni

One pill Once daily

12 weeks (8 weeks OK if VL<6 million)

12weeks

Paritaprevir(150 mg)/Ritonavir (100 mg)/Ombitasvir (25 mg) plus twice-daily dosed Dasabuvir (250 mg) and weight-based RBV (1000 mg [<75 kg] to 1200 mg [>75 kg])

Once daily 12 weeks 24 weeks

Sofosbuvir (400 mg) + Simeprevir (150 mg)

Once daily 12 weeks 24 weeks (not FDA approved)

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HCV Treatment Guidelines (VA) www.hepatitis.va.gov/pdf/treatment-considerations-2015-02.pdf

5/20/2015

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Monthly Average Wholesale Price of Antiretroviral Drugs

4/8/15 DHHS Guidelines http://aidsinfo.nih.gov/guidelines/html/1/adult-

and-adolescent-treatment-guidelines/0

ART STRENGTH DOSING #/MO. AWP

Tenofovir Disoproxil Fumarate/ Emtricitabine (Truvada)

300/200 mg 1 tab daily 30 $1,539.90

Zidovudine/Lamivudine Generic 300/150 mg 1 tab twice 60 $931.61

Dolutegravir/Abacavir/Lamivudine (Triumeq )

50/600/300 mg tab

1 tab daily 30 $2,648.84

Elvitegravir/Cobicistat/Tenofovir Disoproxil Fumarate/ Emtricitabine (Stribild)

150/150/300/200 mg tab

1 tab daily 30 $2,948.70

clinicaloptions.com/hiv

2015 Conference on Retroviruses and Opportunistic Infections

Studies 104/111: Tenofovir Alafenamide

Fumarate vs TDF in Treatment-Naive Pts

Parallel, randomized, double-blind, active-controlled phase III studies

Primary endpoint: HIV-1 RNA at Wk 48

TAF/FTC/EVG/COBI*

single-tablet regimen

(n = 866)

TDF/FTC/EVG/COBI†

single-tablet regimen

(n = 867)

Treatment-naive

HIV-infected pts with

HIV-1 RNA ≥ 1000 copies/mL,

eGFR ≥ 50 mL/min

(N = 1733)

Stratified by HIV-1 RNA,

CD4+ cell count,

geographic region

Wk 48

Primary endpoint Wk 144

*10/200/150/150 mg once daily. †300/200/150/150 mg once daily.

Wohl DA, et al. CROI 2015. Abstract 113LB.

5/20/2015

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clinicaloptions.com/hiv

2015 Conference on Retroviruses and Opportunistic Infections

Virologic

Success*

Virologic

Failure

No Data

Studies 104/111: TAF Noninferior to TDF at

Week 48 TAF also noninferior to TDF at Wk 48 in

each study (104 and 111)

Results similar across all baseline virologic and demographic subgroups

7 pts in TAF arm and 5 pts in TDF arm with NRTI resistance at VF

– 1 in TAF arm and 2 in TDF arm with combined M184V/I + K65R

5 pts in TAF arm and 3 pts in TDF arm with INSTI resistance at VF

0.9% in TAF arm and 1.5% in TDF arm discontinued due to AE

CD4+ increases greater in TAF arm: 211 vs 181 (P = .024)

Pts

(%

)

92 90

Δ +2.0%

(95% CI: -0.7% to +4.7)

TAF/FTC/EVG/COBI

(n = 866)

TDF/FTC/EVG/COBI

(n = 867)

0

20

40

60

80

100

4 4 4 6

n =

*HIV-1 RNA < 50 c/mL as defined by FDA Snapshot algorithm Discontinued for AE, death, or missing data.

800 784

Wohl DA, et al. CROI 2015. Abstract 113LB. Reproduced with permission.

COMMON INFECTION

TREATMENT CURE RATE COST

Onychomycosis (Nail fungus)

Terbinafine 250mg 1 pill daily x 6-12 w

76% <$25

Helicobacter pylori

PPI/Amoxicillin/Clarithromycin 4 pills twice daily for 10- 14 days.

80% <$100

Latent Tuberculosis

Isoniazid 300mg 1 pill daily x 6-9m

60-90% <$40

Urinary Tract Infection

Nitrofurantoin 100 mg 1 pill twice daily for 5 days

90-95% <$10

Chlamydia Azithromycin 500mg 2 pills in one single dose

96% <$5

Hepatitis C Genotype 1A

Sofosbuvir/Ledipasvir 1 pill daily x 8-12 weeks

95+% $63,000-$94,500

Curing Common Infections: Simplicity, Effectiveness, and Price

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Cost of HCV treatment Genotype 1A

Daily pill burden

Frequency Cost

12 weeks Sofosbuvir/Ledipasvir (Harvoni)

1 tablet Once daily $94,500

12-24 weeks Viekira Pak+ Ribavirin 9-10 pills Twice daily $87,000

12 weeks Sofosbuvir+-Pegylated Interferon+ Ribavirin

6-7 pills + weekly shot

Twice daily $100,340

Hepatitis C treatment

• Societal perspective:

– Cost-effective

– Expensive

• Individual perspective : (Patient or prescriber) no-brainer

Cost-effectiveness of novel regimens for the treatment of hepatitis C virus. Ann Intern Med 2015 Mar 17; 162:407. (http://dx.doi.org/10.7326/M14-1152 ) Cost-effectiveness and budget impact of hepatitis C virus treatment with sofosbuvir and ledipasvir in the United States. Ann Intern Med 2015 Mar 17; 162:397. (http://dx.doi.org/10.7326/M14-1336)

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clinicaloptions.com/hiv

2015 Conference on Retroviruses and Opportunistic Infections

LATTE: Cabotegravir (GSK1265744) + RPV

as Maintenance ART: Wk 96 Results Cabotegravir, DTG analogue with long half-life, oral or injectable formulations

Randomized, dose-ranging phase IIb study of oral formulation

Primary endpoint: HIV-1 RNA < 50 c/mL at Wk 48

CAB 10 mg QD + RPV 25 mg QD

CAB 30 mg QD + RPV 25 mg QD

*Pts with HIV-1 RNA < 50 c/mL at Wk 24 continued to maintenance phase. TDF/FTC or ABC/3TC.

ART-naive pts,

HIV-1 RNA

≥ 1000 c/mL

(N = 243) CAB 60 mg QD + RPV 25 mg QD

EFV 600 mg QD + 2 NRTIs QD (n = 62)

Margolis D, et al. CROI 2015. Abstract 554LB.

CAB 10 mg QD + 2 NRTIs

(n = 60)

CAB 30 mg QD + 2 NRTIs

(n = 60)

CAB 60 mg QD + 2 NRTIs

(n = 61)

Wk 48

primary analysis Stratified by HIV-1 RNA

(≤ vs > 100,000 c/mL) and NRTI Wk 24

Induction Phase* Maintenance Phase

Wk 96

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clinicaloptions.com/hiv

2015 Conference on Retroviruses and Opportunistic Infections

LATTE: Virologic Success Through

Maintenance Wk 96

6 pts in CAB arms with PDVF at Wk 96; 4 additional pts since Wk 48

– 3 pts in CAB 10-mg arm with treatment-emergent NNRTI resistance; 1 of these with both NNRTI + INSTI RAMs but decreased ARV exposure in PK analysis

Margolis D, et al. CROI 2015. Abstract 554LB. Reproduced with permission.

HIV

-1 R

NA

< 5

0 c

/mL

by

Sn

ap

sh

ot A

lgo

rith

m (

%)

100

80

60

40

20

0

BL 4 12 24 28 36 48 72 96

Induction Phase Maintenance Phase

CAB 10 mg (n = 60)

CAB 30 mg (n = 60)*

CAB 60 mg (n = 61)

EFV 600 mg (n = 62)

68% 63%

84%

75%

Wks *CAB 30 mg selected for future development

Will future once pill once daily coformulations will be better?

• Dolutegravir is superior to Darunavir/ritonavir

FLAMINGO 96 weeks results Lancet HIV April 2015:

www.sciencedirect.com/science/article/pii/S2352301815000272

• Tenofovir Alanfenamide/Emtricitabine/ Darunavir/Cobicistat (www.metropolismedical.net )

• Tenofovir Alanfenamide/Emtricitabine/ Rilpivirine (Optimus Medical Group in SF)

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