1/14/2019

1

Simplifying HIV Treatment

Now and in the Future

David M. Hachey, Pharm.D., AAHIVP

Professor

Idaho State University

Department of Family Medicine

Disclosure

• Nothing

1/14/2019

2

Objectives

• List current first line agents for the treatment of

HIV

• Describe two ways HIV regimens may be

simplified

• Identify the role of newly approved agents

• Educate patients about future approaches to the

treatment of HIV

• Discuss primary care prevention strategies to

reduce morbidity and mortality

GETTING TO 2019

WHAT DO WE KNOW

1/14/2019

3

CASE

• ”Jane” is 32 year old African American female

living with HIV for 10 years. Her CD4 count is

550 cells/mm and her viral load is undetectable.

She currently takes the following

– Kaletra (lopinavir/ritonavir) 2 tablets BID

– Combivir (zidovudine/lamivudine) 1 tablet BID

• Is ”Jane”:

– Meeting goals of therapy?

– Receiving the standard of care?

Transmission Risk Factors

1/14/2019

4

Ethnicity Distribution

Why…

1/14/2019

5

HIV Care Cascade

1/14/2019

6

1/14/2019

7

1/14/2019

8

1/14/2019

9

Goals of Therapy

Goals of therapy

• Reduce HIV-associated

morbidity and prolong the

duration and quality of

survival

• Restore and preserve

immunologic function

• Maximally and durably

suppress plasma HIV

viral load

• Prevent HIV transmission

Evidence and support

• Reduces HIV-related

morbidity and mortality

• Decreased perinatal

transmission

• Reduced CVD and other

EOD

• Delays drug-resistance

mutations

1/14/2019

10

Drug Approval Timeline

Zidovudine

Didanosine

Zacitabine

Stavudine

Lamivudine Saquinavir

Indinavir Nevirapine Ritonavir

Combivir Delaviridine

Nelfinavir

Abacavir Efavirenz

Kaletra

Trizivir

Tenofovir DF

Atazanavir Emtricitabine

Enfurvitide

Fosamprenavir

Epzicom

Truvada

Tipranavir

Raltegravir

Atripla

Darunavir

Maraviroc

Etravirine

Complera Rilpivirine

Stribild

Dolutegravir

Triumeq

Genvoya Prezcobix

Descovy

Odefsey

Juluca

Biktarvy Cimduo

Delstrigo Doravirine

Ibalizumab Symtuza

1981 1990 1995 2000 2005 2010 2015

1/14/2019

11

Standard Approach to Therapy

• Choose one Anchor Drug from one of

the following classes

– Integrase inhibitors

– Protease inhibitors

– Non-nucleoside reverse transcriptase

inhibitors

• Choose a Backbone consisting of

– Two nucleoside reverse transcriptase

inhibitors

Recommended Initial Regimens

for Most PLWH Class Therapy Pill Burden

INSTI-Based

Raltegravir + Tenofovir-Emtricitabine AM PM

Dolutegravir-Abacavir-Lamivudine

Dolutegravir + Tenofovir-Emtricitabine

Bictegravir-Tenofovir AF-Emtricitabine

1/14/2019

12

SIMPLIFICATION

WHY AND HOW

CASE

• ”Jane” inquires when picking up her medications

that she has heard there are newer agents for

treatment of HIV. She states this is her only

regimen she has taken, has always been

adherent, and has no resistance. Her copay is

$25 per medication and she states that is a

barrier for her.

– Describe to ”Jane” two benefits of simplifying her

regimen

– Recommend one single-tablet regimen ”Jane” could

use to simplify

1/14/2019

13

Rationale for Simplifying

• Managing or

preventing side

effects

– Limit exposure

• Reducing pill burden

• Avoiding food

restrictions

• Reducing/eliminating

drug interactions

• Eliminating drug-

disease risks

• Lower costs /

insurance

requirements

• Updating to a

‘preferred regimen’

• Higher barrier to

resistance

Potency and Genetic Barrier to

Resistance

Modified from: Tang MW, Shafer RW. Drugs. 2012:72:e1-e25.

Potency

Bar

rie

r to

Re

sist

ance

c-r/DRV

DTG

r/LPV

MVC

c-r/ATV

RAL

EFV

ENF

ETR

ABC ddI

ZDV D4T

3TC FTC

TDF TAF

BIC

NVP

RPV

EVG

Backbone Anchor

1/14/2019

14

Single Tablet Regimens

• There are currently nine single tablet

regimens that contain an anchor drug and

two backbone agents

– 4 contain an anchor drug with high barrier to

resistance and high potency

– Reduces copay and allows for complete

regimen administration

Two-Drug Regimens

• There have been 8 clinical trials examining

two-drug simplification

– Candidates for these studies generally have

high adherence rates and no drug resistance

1/14/2019

15

Two-Drug Simplification

Dolutegravir-Rilpivirine

• Juluca® (FDA approved)

• Patients need to be

suppressed for 6 months

on 3-drug regimen before

switch

• No resistance

• Adhere to food

requirements

Dolutegravir-Lamivudine

70

85 89

90

93

91 93

[CELLREF]

72

87 89

88

93

90 91

-20

0

20

40

60

80

100

-4 0 4 8 12 16 20 24 28 32 36 40 44 48 H

IV-1

RN

A <

50

c/m

L, %

b

Study visit

DTG + 3TC (N=716)

DTG + TDF/FTC (N=717)

Virologic outcome

Not FDA Approved

CASE

Benefits for “Jane

• Reduce side effects

• Reduce pill burden

• Single copay

• Higher barrier to

resistance and more

potent agents

• Avoiding food restrictions

Options for ”Jane”

• 3-drug regimens

– Biktarvy (STR)

• Bictegravir/TAF/FTC

– Triumeq (STR)

• Dolutegravir/3TC/ABC

• 2-drug regimens

– Juluca (STR)

1/14/2019

16

IS NEWER BETTER?

New Agents Since 2015

• Tenofovir Alafenamide (NRTI)

• Bictegravir (Integrase Inhibitor)

• Doravirine (NNRTI)

• Ibalizumab (Entry Inhibitor)

1/14/2019

17

Tenofovir

Tenofovir Diproxil Fumarate (TDF)

• Approved early 2000’s

• Component of several

fixed dosed tablets

– 300 mg

• Long-term toxicities

– Osteoporosis

– Renal problems

• Larger tablets

Tenofovir Alafenamide (TAF)

• Made available 2015

• Component of several

fixed dose tablets

– 25 mg and 10 mg

• Long-term toxicities

– No bone/renal

– Less favorable lipid profile

Tenofovir

1/14/2019

18

Bictegravir

• Integrase inhibitor available as a fixed

dose tablet with NRTI backbone

– Biktarvy®

• Potent and high barrier to resistance

• Favorable drug interaction and side effect

profile

– Headache and insomnia most common, but

rare

Doravirine

• Non-nucleoside

reverse transcriptase

inhibitor available

alone or in

combination with

NRTI backbone

– Pifeltro® - single agent

– Delstrigo® –

combination product

• When compared with

other drugs in it’s

class:

– No interactions with

proton pump inhibitors

– No food restrictions

– Well tolerated

1/14/2019

19

Ibalizumab

• Unique monoclonal antibody that prevents

entry into the CD4 cells

• Given via IV infusion every two weeks

– Needs to be combined with other agents

• High cost

• Reserved for rare circumstances

Is Newer Better

• Tenofovir Alafenamide – Maybe

– Conflicting data, but many providers favor TAF over

TDF

• Bictegravir – YES

– Risen to the top for most providers as the go to drug

• Doravirine – No

– May be used in certain circumstances, but not

necessarily better than other NNRTIs

• Ibalizumab – Maybe

– Novel drug, but specific uses

1/14/2019

20

WHAT’S NEXT

Long-Acting Injectable

• Cabotegravir (INSTI)

+ Rilpivirine (NNRTI)

– Integrase inhibitor with

a high barrier to

resistance and

extremely long half life

– Both agents are able

to be formulated into a

long acting injectable

suspension

96 Week Virologic Outcomes

94

4 2

87

0

13

84

2

14

0

20

40

60

80

100

Virologic success

Virologic nonresponse

No virologic data

HIV

-1 R

NA

<50 c

/mL,

%

CAB + RPV LA Q8W (n=115)

CAB + RPV LA Q4W (n=115)

CAB + NRTIs PO (n=56)

1/14/2019

21

Long-Acting Injectable

What We Know

• Oral lead in

• Injections are high

volume given in the

gluteal muscle

• Need a provider (or

pharmacist?) trained to

administer agent

What We Don’t Know

• Who are going to be the

best candidates

• How will this work in rural

settings

• What happens when

someone becomes non-

adherent

– Resistance risk

• Cost

HIV-1 discovered

ZDV monotherapy ZDV/3TC

Triple Drug Therapy

Single Tablet Regimens

The Integrase Era

Long Acting Injectable?

2-drug regimens

Implantable ART

bNAbs for therapy

1983 1987 1995 1996 2006 2012-13 2019 2025

Future of Antiretroviral Therapy

1/14/2019

22

PRIMARY CARE STRATEGIES

Improving Quality and Duration of Life

Primary Care Management

• Cardiovascular Risk

– Hypertension

– Myocardial infarction

– Hyperlipidemia

• Diabetes

• Chronic kidney

disease

• Osteoporosis

• Smoking

– Lung disease

• Cancer screening

– Colon

– Prostate

– Breast

– Lung

– Cervical

– Anal

1/14/2019

23

HIV Care Cascade

Rapid testing for HIV at the pharmacy

Connecting new patients

to a provider

Late to therapy

calls and 90 day

fills

HIV Prevention

(PrEP)

Pre-Exposure Prophylaxis

(PrEP)

1/14/2019

24

Summary

• List current first line agents for the treatment of

HIV

• Describe two ways HIV regimens may be

simplified

• Identify the role of newly approved agents

• Examine patients about future approaches to the

treatment of HIV

• Discuss primary care prevention strategies to

reduce morbidity and mortality