New and Emerging Therapies for the Clinical Management of HIV Infection

New and Emerging Therapies for the Clinical Management of HIV Infection

Sponsored for CME credit by Rush University Medical Center

Supported by an independent educational grant from Gilead Sciences Medical Affairs

2

CME Disclaimer, Disclosure CME Disclaimer, Disclosure Information, and Slide HandoutsInformation, and Slide Handouts

● CME DisclaimerCME Disclaimer- These slides may not be videotaped, published, posted online, and/or presented for

Continuing Medical Education credit without written permission from Rush University Medical Center and Practice Point Communications

● Disclosure InformationDisclosure Information- It is the policy of the Rush University Medical Center Office of Continuing Medical Education

to ensure that its CME activities are independent, free of commercial bias and beyond the control of persons or organizations with an economic interest in influencing the content of CME

- Everyone who is in a position to control the content of an educational activity must disclose all relevant financial relationships with any commercial interest (including but not limited to pharmaceutical companies, biomedical device manufacturers, or other corporations whose products or services are related to the subject matter of the presentation topic) within the preceding 12 months

- If there are relationships that create a conflict of interest, these must be resolved by the CME Course Director in consultation with the Office of Continuing Medical Education prior to the participation of the faculty member in the development or presentation of course content

● Slide HandoutsSlide Handouts- The enclosed slide handouts are provided for reference purposes only

- The faculty presenter may have customized the slides through reordering or deleting and thus the handouts may not exactly match the presentation

3

EducatorEducator

● Disclosures- Grants/Research Support: n/a- Consultant: n/a- Speakers’ Bureau: Gilead, Janssen- Stock Shareholder: n/a- Other Financial or Material Support: n/a

Lisa Hightow-Weidman, MD, MPHAssociate Professor

University of North Carolina at Chapel Hill

4

Accreditation and DesignationAccreditation and Designation

Rush University Medical Center is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians. Rush University Medical Center designates this live activity for a maximum of 1 AMA PRA Category 1 Credit™. Physicians should claim only credit commensurate with the extent of their participation in the activity.

The University of Florida College of Pharmacy is accredited by the Accreditation Council for Pharmacy Education as a provider of continuing pharmacy education (UAN #0012-9999-13-043-L02-P). This activity is accredited for 1 hour of continuing pharmacy education (CPE) credit. The University of Florida College of Pharmacy will report all credit to CPE Monitor within 30 working days after receiving evidence of successful completion of the course. Successful completion means that you must attend the entire program and complete an evaluation form.

Supported by an independent educational grant from Gilead Sciences Medical Affairs.

ANAC is an approved provider of continuing nursing education (CNE) by the Virginia Nurses Association, an accredited approver by the American Nurses Credentialing Center’s Commission on Accreditation. This activity is approved for 1.0 contact hour by the Association of Nurses in AIDS Care.

5

FacultyFaculty

CME Course DirectorCME Course DirectorHarold A. Kessler, MDProfessor of Medicine and Immunology/Microbiology

Associate Director,Section of Infectious Diseases

Rush University Medical CenterChicago, Illinois

Content Development and TrainingContent Development and TrainingEric S. Daar, MD

Chief, Division of HIV MedicineHarbor-UCLA Medical Center

Torrance, CaliforniaProfessor of Medicine

David Geffen School of Medicine at UCLALos Angeles, California

CME ReviewerCME ReviewerDavid M. Simon, MD, PhD

Associate ProfessorSection of Infectious Diseases

Rush University Medical CenterChicago, Illinois

CNE ReviewerCNE ReviewerAllison R. Webel, RN, PhD

Instructor and KL2 ClinicalResearch Scholar

Frances Payne Bolton School of NursingCase Western Reserve University

Cleveland, Ohio

6

Faculty DisclosuresFaculty Disclosures

CME Course Director:Harold A. Kessler, MD

Content Development and Training:Eric S. Daar, MD

Grants/research support

None Abbott, Gilead Sciences, Merck, Pfizer, ViiV

Consultant None Bristol-Myers Squibb, Gilead Sciences, Merck, ViiV

Speakers’ bureau None None

Stock shareholder

Abbott Laboratories, GlaxoSmithKline, Merck

None

Other financial or material support

None None

7

Faculty DisclosuresFaculty Disclosures

CME Reviewer:David M. Simon, MD, PhD

CNE Reviewer:Allison R. Webel, RN, PhD

Medical Editor:Peter Pinkowish

Grants/research support

None None None

Consultant None None None

Speakers’ bureau

None None None

Stock shareholder

None None None

Other financial or material support

None None None

8

Opinions and Off-Label DiscussionsOpinions and Off-Label Discussions

The opinions or views expressed in this educational program are those of the participants and do not necessarily reflect the opinions or

recommendations of Gilead Sciences Medical Affairs, Rush University Medical Center, the Association of Nurses in AIDS

Care, or the University of Florida College of Pharmacy

The faculty may have included discussion on unlabeled usesof a commercial product or an investigational use of a

product not yet approved for this purpose

Please consult the full prescribing information before usingPlease consult the full prescribing information before usingany medication mentioned in this programany medication mentioned in this program

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New Electronic Evaluation ProcessNew Electronic Evaluation Process

● Please clearly print your information on the Sign-in Sheet

● You will receive an electronic evaluation to the email address provided within 1 business day

● Reminder email communications will be sent up to 5 days post lecture until the evaluation is completed

● Completion Is Required for CME/CNE/CPE credit and future attendance

● Incomplete evaluations will preclude attendees from receiving their CME/CNE/CPE certificate & future communications about lectures in your area

10

Learning ObjectivesLearning Objectives(CME/CNE and CPE)(CME/CNE and CPE)

● Upon completion of this activity, the participant intends to incorporate the following objectives into their practice of medicine and/or advance practice nursing:

- Appropriately select antiretroviral therapy for my HIV-infected patients according to the guideline recommendations by the Department of Health and Human Services

- Counsel my HIV-infected patients on the benefits and risks associated with antiretroviral therapy

- Counsel my HIV-infected patients on new potential drug targets against HIV infection

- Counsel my HIV-infected patients how HIV agents in late-stage clinical development may impact future management of HIV-infected patients

CME/CNECME/CNE● Upon completion of this activity, the

pharmacist should be able to:

- Recommend antiretroviral therapy for my HIV-infected patients according to the guideline recommendations by the Department of Health and Human Services

- Counsel my HIV-infected patients on the benefits and risks associated with antiretroviral therapy

- Counsel my HIV-infected patients on new potential drug targets against HIV infection

- Counsel my HIV-infected patients how HIV agents in late-stage clinical development may impact future management of HIV-infected patients

CPECPE

11

Program Overview

● Treatment challenges/clinical needs

● New antiviral drugs/formulations

12

Worldwide Treatment andPrevention Gaps (2011)

● On ART: 8 million

● Number needing ART: 15 million

● New infections: 2 million

● People were waiting to become treatment-eligible, sicken, or die: ~24 million

● Estimated coverage of ART in low- and middle-income countries: 36%

Granich R, et al. Curr Opin HIV AIDS. 2013;8:41-49.

13

Chronic HIV in the US:Underdiagnosed and Undertreated

Nu

mb

er (

in ‘

000s

)

Prevalence Diagnosed Treated

1,106,400-1,200,000

874,056-960,000

437,028-489,600

~80%Diagnosed

~40%Treated

Smith MK, et al. PLoS One. 2012;9:e1001260.Gardner EM, et al. Clin Infect Dis. 2011;52:793-800.Burns DN, et al. Clin Infect Dis. 2010;51:725-731.

~20% of AllHIV-Infected Are HIV RNA

<50 copies/mL

209,773-376,992

Viral Suppression

14

No Single, Stand-Alone HIV Prevention Intervention Will Halt the HIV Pandemic

● Over the past 30 years, existing prevention strategies have had limited to no success

- Education about risks

- Behavioral interventions to decrease risk

- Harm reduction

- Vaccines

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The Shift Towards EarlierInitiation of Antiretroviral Therapy

● Newer ART regimens

- Generally better tolerated, more convenient, and more potent than older regimens

● Survival benefit

- Randomized controlled trials

- Observational cohort data

● Untreated HIV

- Maybe associated the development of non-AIDS-defining illness

● Biologic rationale

● Effective ART reduces HIV transmission

16

Simultaneous Use of Different Classes of Prevention Strategies

BiomedicalInterventions

StructuralInterventions

CommunityInterventions

Individual andSmall GroupBehavioral

Interventions

HIV Testing,Linkage to Care,Expanded ART

CoverageCombinationHIV

Prevention

17

FDA Approves First Drug for Reducing the Risk of Sexually Acquired HIV Infection (July 16, 2012)

● Emtricitabine/tenofovir DF

- Indicated in combination with safer sex practices for pre-exposure prophylaxis (PrEP) to reduce the risk of sexually acquired HIV-1 infection in adults at high risk

• Other prevention methods (eg, safe sex practices, risk reduction counseling, and regular HIV testing)

● Revised PrEP Boxed Warning

- Use in those who are confirmed HIV-negative prior to prescribing the drug and at least every 3 months during use

- Contraindicated in those with unknown or positive HIV status

● Gilead Sciences conditions of PrEP approval

- Collect viral isolates from individuals who acquire HIV while taking emtricitabine/tenofovir DF and to evaluate these isolates for the presence of resistance

- Collect pregnancy outcomes data for women who become pregnant while taking emtricitabine/tenofovir DF for PrEP

- Conduct a trial to evaluate drug adherence and its relationship to adverse events, risk of seroconversion, and resistance development in seroconverters

Available at: http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm312210.htm.

18

CDC Interim Guidance: PrEP in Heterosexually Active Adults and MSM

● Interim guidance as part of a comprehensive set of HIV prevention services

● PrEP has the potential to contribute to effective and safe HIV prevention for if it is:

- Targeted to those at high risk for HIV acquisition

- Delivered as part of a comprehensive set of prevention services

• Risk reduction and PrEP adherence counseling

• Ready access to condoms

• Diagnosis and treatment of STIs

- Accompanied by monitoring HIV status, side effects, adherence, and risk behavior

CDC. MMWR Morb Mortal Wkly Rep. 2011;60:65-68.CDC. MMWR Morb Mortal Wkly Rep. 2012;61:586-589.

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● Proof of efficacy study of topical tenofovir gel in women- CAPRISA 004

● First oral PrEP study of emtricitabine/tenofovir DF for MSM- iPrEx

● Proof of efficacy studies in young, heterosexual adults in Africa- Partners PrEP

- TDF2 (CDC4940)

● Early termination due to futility of PrEP in women- FEM-PrEP

- VOICE (oral tenofovir DF and topical tenofovir arms only)

PrEP Trial Results

20

CDC Interim Guidance for HealthcareProviders: Beginning PrEP Medication Regimen

● Prescribe emtricitabine/tenofovir DF (200/300 mg)

- 1 tablet daily

● In general, prescribe no more than a 90-day supply

- Renew only after confirming patient remains HIV uninfected

● If HBV infected

- Consider emtricitabine/tenofovir DF for HBV and HIV prevention

● Provide risk-reduction and PrEP medication adherence counseling and condoms


21

CDC Interim Guidance for HealthcareProviders: Follow-Up While on PrEP

● Evaluate and support PrEP medication adherence at each follow-up visit (more often if needed)

- For women, conduct pregnancy test

● Every 2 to 3 months

- HIV antibody test (document negative result)

- Assess

• Risk behaviors and provide risk-reduction counseling and condoms

• STI symptoms (if present, test and treat as needed)

● Every 6 months

- Test for STI regardless of symptomatology (treat as needed)

● Every 3 months after initiation, then yearly while on PrEP

- Blood urea nitrogen

- Serum creatinine


22

CDC Interim Guidance for HealthcareProviders: Discontinuing PrEP

● Perform HIV test(s) to confirm HIV status

- If positive

• Order and document results of resistance testing

• Establish linkage to care

• For pregnant women, inform prenatal-care provider and coordinate care to maintain HIV prevention during pregnancy and breastfeeding

- If negative

• Establish linkage to risk-reduction support services as indicated

● If active HBV infection at initiation of PrEP

- Consider appropriate medication for continued treatment of HBV infection


23

Program Overview



24

DHHS Guidelines:When To Start Perspectives

● Untreated HIV infection may have detrimental effects at all stages of infection

- Effects of immune deficiency, direct effects of HIV on specific end organs, and the indirect effects of HIV-associated inflammation on these organs

● Earlier treatment may prevent the damage associated with HIV replication during early stages of infection

- Sustaining viral suppression and maintaining higher CD4 count via ART delays or prevents some non-AIDS-defining complications and disorders

● Success of ART hinges on avoiding treatment interruptions

DHHS. Available at: http://www.aidsinfo.nih.gov/ContentFiles/AdultandAdolescentGL.pdf. Revision February 12, 2013.

25

When to Start Treatment

Clinical CategoryCD4 Count (cells/mm3)

HIV RNA(copies/mL)

2/2013DHHS

Guidelines

2012IAS-USA

Guidelines

AIDS-defining illness or severe symptoms

Any value Any value Treat

Asymptomatic <500 Any value Treat

>500 Any value Treat

Pregnant women Any value Any value Treat

HIV-associated nephropathy Any value Any value Treat

HIV/HBV coinfection when HBV treatment is indicated

Any value Any value Treat

DHHS. Available at: http://www.aidsinfo.nih.gov/ContentFiles/AdultandAdolescentGL.pdf. Revision February 12, 2013; Thompson MA, et al. JAMA. 2012;308:387-402.

The IAS-USA guidelines also recommends initiating antiretroviral therapy in HIV-infected patients with active hepatitis C virus infection, active or high risk for cardiovascular disease, and symptomatic primary HIV infection.

26

DHHS Guidelines: Preferred Regimens

NNRTI Efavirenz1/emtricitabine2/tenofovir DF3

PI Atazanavir4 + ritonavir + emtricitabine2/tenofovir DF3

Darunavir + ritonavir (qd) + emtricitabine2/tenofovir DF3

INSTI Raltegravir + emtricitabine2/tenofovir DF3

Pregnant women

Lopinavir/r bid + zidovudine/lamivudine2

INSTI: Integrase strand transfer inhibitors. 1Efavirenz should not be used during the first trimester of pregnancy or in women trying to conceive or not using effective and consistent contraception.2Lamivudine may substitute for emtricitabine or visa versa.3Tenofovir DF should be used with caution in patients with renal insufficiency.4Atazanavir + RTV should not be used in patients who require >20 mg omeprazole equivalent/day.


27

DHHS Guidelines: Alternative Regimens

NNRTI Efavirenz + (abacavir1 or zidovudine)/lamivudine2

Rilpivirine3/emtricitabine2/tenofovir DF

Rilpivirine3 + abacavir/lamivudine2

PI Atazanavir + ritonavir + abacavir/lamivudine2

Darunavir + ritonavir + abacavir/lamivudine2

Fosamprenavir + ritonavir (qd or bid) + abacavir/lamivudine2 or emtricitabine2/tenofovir DF

Lopinavir/r4 (qd or bid) + abacavir/lamivudine2 or emtricitabine2/tenofovir DF

INSTI Raltegravir + abacavir/lamivudine2

Elvitegravir/cobicistat/emtricitabine/tenofovir DF5

1Abacavir should not be used in patients who test positive for HLA-B*5701. Use abacavir with caution in patients with high risk of cardiovascular disease or pretreatment HIV RNA >100,000 copies/mL.2Lamivudine may substitute for emtricitabine or visa versa.3Use rilpivirine with caution in patients with pretreatment HIV RNA >100,000 copies/mL.

4Once-daily lopinavir/r is not recommended in pregnant women.5Patients with creatinine clearance >70 mL/min.


28

No One Right Option for Everyone:Limitations of Current First-Line Regimens

● Efavirenz-based regimens

- Not recommended for women at risk of becoming pregnant

- CNS toxicity

- Rash

- Low barrier to resistance

● Raltegravir-based regimens

- Twice-daily administration

- Relatively low barrier to resistance

- Lack of second-line integrase inhibitor option

● Ritonavir-boosted PI-based regimens

- Higher pill count

- Gastrointestinal toxicity

29

Simplified and Convenient ART:Achieving Goals of Therapy

● Treatment goals

- 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

● Individualize strategies to achieve goals

- Tailor regimens to enhance adherence

- Pretreatment genotypic resistance testing

- Maximize conditions to promote ART adherence


30

Potential Therapeutic Targets

Reverse Transcriptase

Inhibitors

Protease Inhibitors

FusionInhibitors

CytoplasmCytoplasm

NucleusNucleus

CCR5Inhibitors

Integrase Inhibitors

31

Program Overview



32

Study 102: QUAD Versus Efavirenz/Emtricitabine/Tenofovir DF

Phase 3 study(192 weeks)

Treatment-naïveDouble-blind

HIV RNA >5000 copies/mLAny CD4 countNon-inferiority(12% margin)

Sax PE, et al. Lancet. 2012;379:2439-2448.Zolopa A, et al. J Int AIDS Soc. 2012;15(suppl 4):18219. Abstract O424a.

Single-Tablet, Once-Daily Regimens

Randomization1:1

Efavirenz 600 mg/Emtricitabine/Tenofovir DF (n=352)

Elvitegravir 150 mg/Cobicistat 150 mg/Emtricitabine/Tenofovir DF (n=348)

PrimaryEndpointWeek 48

HIV RNA<50 Copies/mL

33

Study 102:Baseline Demographics


34

Study 102:Virologic and Immunologic Outcomes

Pat

ien

ts (

%)

HIV RNA <50 Copies/mL CD4 Cell Gain

88%

48(n=348/352)

96(n=348/352)

84%

CD

4 G

ain

(c

ell

s/m

m3 )

239*

295

*P=0.009.

Difference (%):Difference (%):3.6 (-1.6, 8.8)3.6 (-1.6, 8.8)

84% 82%


206

273

EVG/COBI/FTC/TDF EFV/FTC/TDF

Week



48(n=325/315)

96(n=307/302)

Week

35

Study 102: Virologic Outcomesby Baseline HIV RNA

Pat

ien

ts (

%)

Baseline HIV RNA <100K Copies/mL

90%

48(n=348/352)

96(n=230/236)

85% 86%81%


Week


Pat

ien

ts (

%)

Baseline HIV RNA >100K Copies/mL

84%

48(n=348/352)

96(n=230/236)

82% 81% 83%


Week

36

Study 102 (Week 96):NNRTI, Integrase, and NRTI Resistance

Zolopa A, et al. J Int AIDS Soc. 2012;15(suppl 4):18219. Abstract O424a.

37

Study 102 (Week 96):Safety and Tolerability

Week 96

Zolopa A, et al. J Int AIDS Soc. 2012;15(suppl 4):18219. Abstract O424a.

38

Study 103: QUAD VersusAtazanavir/r + Emtricitabine/Tenofovir DF

Phase 3 study(192 weeks)

Treatment-naïveDouble-blind

HIV RNA >5000 copies/mLAny CD4 countNon-inferiority(12% margin)

Randomization1:1

Atazanavir/r +Emtricitabine/Tenofovir DF (n=355)

DeJesus E, et al. Lancet. 2012;379:2429-2438.Rockstroh J, et al. J Int AIDS Soc. 2012;15(suppl 4):18220. Abstract O424b.

Elvitegravir/Cobicistat/Emtricitabine/Tenofovir DF (n=353)



Once-Daily Regimens

39

Study 103:Baseline Demographics


40

Study 103:Virologic and Immunologic Outcomes

Pat

ien

ts (

%)


90%

48(n=353/355)

96(n=353/355)

87%

CD

4 G

ain

(c

ell

s/m

m3 ) 207

256


83% 82%


211

261

EVG/COBI/FTC/TDF ATV/r + FTC/TDF

Week

48(n=334/321)

96(n=316/315)

Week



41

Study 103: Virologic Outcomesby Baseline HIV RNA

Pat

ien

ts (

%)

Baseline HIV RNA <100K Copies/mL

93%

48(n=203/214)

96(n=203/214)

90%84% 84%


Week

Pat

ien

ts (

%)

Baseline HIV RNA >100K Copies/mL

85%

48(n=150/141)

96(n=150/141)

82% 82% 80%


Week


42

Study 103 (Week 96):Resistance

Rockstroh J, et al. J Int AIDS Soc. 2012;15(suppl 4):18220. Abstract O424b.

43

Study 103 (Week 96):Safety and Tolerability

Rockstroh J, et al. J Int AIDS Soc. 2012;15(suppl 4):18220. Abstract O424b.

44

Elvitegravir/Cobicistat/Emtricitabine/Tenofovir DF:Dosing and Safety Considerations

● Meal restrictions

- Take with meal

● Adverse events

- Diarrhea, nausea

• Comparable with ATV/r, usually mild and rarely leads to drug discontinuation

- Early decrease in estimated GFR from cobicistat

• Generally benign if <0.4 mg/dL increase in creatinine

- Drug-drug interactions: may be similar to ritonavir-boosted PI, do not use with other PIs

● Elvitegravir and raltegravir share similar resistance pathways (cross resistant)

DHHS. Available at: http://www.aidsinfo.nih.gov/ContentFiles/AdultandAdolescentGL.pdf. Revision February 12, 2013.Johnson VA, et al. Top Antivir Med. 2011;19:156-164.

45

ECHO and THRIVE Studies:Study Design (96 Weeks)

Phase 3 Studies Treatment-naïve, HIV RNA >5000 copies/mL, no NNRTI resistance-associated mutations

Randomization1:1

Efavirenz 600 mg qd +Emtricitabine/Tenofovir DF qd

Primary endpoint: non-inferiority at week 48 (lower confidence interval <12%).Primary endpoint: non-inferiority at week 48 (lower confidence interval <12%).*Investigator*Investigator’’s choice: emtricitabine/tenofovir DF, zidovudine/lamivudine, abacavir/lamivudine.s choice: emtricitabine/tenofovir DF, zidovudine/lamivudine, abacavir/lamivudine.

Cohen M, et al. AIDS. 2012;Dec 3. [Epub ahead of print].Molina J-M, et al. Lancet. 2011;378:238-246.Cohen CJ, et al. Lancet. 2011;378:229-237.

Rilpivirine 25 mg qd +Emtricitabine/Tenofovir DF qd

ECHO(n=690)

Randomization1:1

Efavirenz 600 mg qd +2 NRTIs

Rilpivirine 25 mg qd +2 NRTIs*

THRIVE(n=678)

46

ECHO and THRIVE Studies:Baseline Demographics

ECHO THRIVE


47

ECHO and THRIVE Studies:HIV RNA <50 Copies/mL(ITT-TLOVR)

Rilpivirine Efavirenz

Pat

ien

ts (

%)

ECHO(n=346/344)

THRIVE(n=340/338)

Pooled Data(n=686/682)

83%


83% 86%82%

78% 78%

Week 48

CD4+196

cells/µL

CD4+182

cells/µL

CD4+189

cells/µL

CD4+171

cells/µL

CD4+228

cells/µL

CD4+219

cells/µL

Week 96

48

Pooled ECHO/THRIVE Post-Hoc Analysis:HIV RNA <50 Copies/mL (Week 96)

0

20

40

60

80

100

HIV

RN

A <

50 C

op

ies/

mL

(%

)

By Baseline HIV RNA(copies/mL)

By Baseline CD4(cells/mm3)

84%

70%

<100K(n=368/329)


80%75%

All patients received emtricitabine/tenofovir DF.Cohen M, et al. AIDS. 2012;Dec 3. [Epub ahead of print].

>100K(n=318/353)

0

20

40

60

80

100

HIV

RN

A <

50 C

op

ies/

mL

(%

)

56%

71%

<50(n=34/36)


69%75%

50-<200(n=194/175)

81% 79%

85%79%

200-<350(n=313/307)

>350(n=144/164)

49

Pooled ECHO/THRIVE (Week 96):Discontinuations and Virologic Failure

Cohen M, et al. AIDS. 2012;Dec 3. [Epub ahead of print].

50

Pooled ECHO/THRIVE (Week 96):Safety

Cohen M, et al. AIDS. 2012;Dec 3. [Epub ahead of print].*P<0.0001 and †P=0.0039 versus rilpivirine.

51

ECHO/THRIVE:Conclusions

● Efficacy

- Week 0-48: rilpivirine was non-inferior to efavirenz

- Week 48-96: comparable between rilpivirine and efavirenz arms

- Better rilpivirine response: baseline HIV RNA <100K versus >100K copies/mL

● Overall virologic failure rate

- Week 0-48: higher in the rilpivirine arm

- Weeks 48-96: similar increases in rilpivirine and efavirenz arms

● Resistance with virologic failure

- Rilpivirine: 6.4%; efavirenz: 2.3%

● Safety

- Lower incidence of adverse events of interest compared with efavirenz

- Most adverse events emerge during the first 4 weeks of therapy

Cohen M, et al. AIDS. 2012;Dec 3. [Epub ahead of print].Molina J-M, et al. Lancet. 2011;378:238-246.Cohen CJ, et al. Lancet. 2011;378:229-237.Rashbaum B, et al. 51st ICAAC. Chicago, 2011. Abstract H2-805.Rimsky L, et al. JAIDS. 2012;59:39-46.

52

STAR Study:Design (96 Weeks)

Randomization1:1

Efavirenz/Emtricitabine/Tenofovir DFOnce Daily

Cohen C, et al. J Int AIDS Soc. 2012;15(suppl 4):18221. Abstract O425.

Emtricitabine/Rilpivirine/Tenofovir DFOnce Daily

Phase 3b study(96 weeks)

Treatment-naïve

Open-labelHIV RNA >2500 copies/mL

Any CD4 countGenotypic sensitivity(EFV, FTC, RPV, TDF)

Non-inferiority(12% margin)

Single-Tablet, Once-Daily Regimens



53

STAR Study:Baseline Demographics


54

STAR Study (Week 48):Virologic and Immunologic Outcomes

Pat

ien

ts (

%)


85.8%

FTC/RPV/TDF(n=394)

EFV/FTC/TDF(n=392)

81.6%

CD

4 G

ain

(ce

lls/m

m3 )

200191

P=0.34


Non-inferiority criteria met.

FTC/RPV/TDF(n=394)

EFV/FTC/TDF(n=392)


55

STAR Study (Week 48):Virologic Outcomes By Baseline HIV RNA

Pat

ien

ts (

%)

HIV RNA <50 Copies/mL) Virologic Failure

89%

80%

<100K(n=260/250)

FTC/RPV/TDF EFV/FTC/TDF

82% 82%

>100K(n=134/142)


Baseline HIV RNA

Difference (%):Difference (%):7.2 (1.1, 13.4)7.2 (1.1, 13.4) Difference (%):Difference (%):

-1.8 (-11.1, 7.5)-1.8 (-11.1, 7.5)

Pat

ien

ts (

%)

5%10%

<100K(n=260/250)

FTC/RPV/TDF EFV/FTC/TDF

3%9%

>100-500K(n=98/117)

Baseline HIV RNA

>500K*(n=36/25)

25%

16%

*Analysis of the >500K stratum was a post-hoc.

56

Emtricitabine/Rilpivirine/Tenofovir DF:Dosing and Safety Considerations

● Meal restrictions

- Take with meal

● Drugs that increase gastric pH (eg, proton-pump inhibitors) may decrease plasma concentrations of rilpivirine

● Adverse events (less common with rilpivirine compared with efavirenz)

- Rash

- Neuropsychiatric symptoms

● Resistance (rilpivirine)

- Most common RAM is E138K (leads to cross resistance to etravirine)

DHHS. Available at: http://www.aidsinfo.nih.gov/ContentFiles/AdultandAdolescentGL.pdf. Revision February 12, 2013.Johnson VA, et al. Top Antivir Med. 2011;19:156-164.

57

Evidence Supports Combination ART for Prevention of HIV Transmission

● Transmission only occurs from persons with HIV

● HIV RNA level is single greatest risk factor for HIV transmission

● Combination ART can lower HIV RNA level to undetectable levels

● Observational evidence in heterosexual couples

● Previous modeling work suggests considerable potential

● Knowing one’s HIV status is key to prevention with combination ART

● When to start combination ART is not known for certainty

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New Electronic Evaluation ProcessNew Electronic Evaluation Process

● Please clearly print your information on the Sign-in Sheet

● You will receive an electronic evaluation to the email address provided within 1 business day

● Reminder email communications will be sent up to 5 days post lecture until the evaluation is completed

● Completion Is Required for CME/CNE/CPE credit and future attendance

● Incomplete evaluations will preclude attendees from receiving their CME/CNE/CPE certificate & future communications about lectures in your area

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Outcomes Measurement ReminderOutcomes Measurement Reminder

● We are required to assess “changes in learners’ competence, performance or patient outcomes achieved as a result of their participation in a CME/CNE/CPE sponsored educational activity”

● As a result of this requirement you will receive a short survey via email 8 to 12 weeks after completing this course

- We consider the survey to be an additional component of your overall participation in this educational activity and would urge you to reflect on what you learned in the activity and then complete this survey

New and Emerging Therapies for the Clinical Management of HIV Infection

Documents

Transcript of New and Emerging Therapies for the Clinical Management of HIV Infection