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

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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

cme disclaimer disclosure information and slide handouts
CME Disclaimer, Disclosure Information, and Slide Handouts
  • CME 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 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 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
educator
Educator

Lisa Hightow-Weidman, MD, MPH

Associate Professor

University of North Carolina at Chapel Hill

  • Disclosures
    • Grants/Research Support: n/a
    • Consultant: n/a
    • Speakers’ Bureau: Gilead, Janssen
    • Stock Shareholder: n/a
    • Other Financial or Material Support: n/a
accreditation and designation
Accreditation 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.

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.

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.

faculty
Faculty

CME Course Director

Harold A. Kessler, MD

Professor of Medicine and Immunology/Microbiology

Associate Director,

Section of Infectious Diseases

Rush University Medical Center

Chicago, Illinois

Content Development and Training

Eric S. Daar, MD

Chief, Division of HIV Medicine

Harbor-UCLA Medical Center

Torrance, California

Professor of Medicine

David Geffen School of Medicine at UCLA

Los Angeles, California

CME Reviewer

David M. Simon, MD, PhD

Associate Professor

Section of Infectious Diseases

Rush University Medical Center

Chicago, Illinois

CNE Reviewer

Allison R. Webel, RN, PhD

Instructor and KL2 Clinical

Research Scholar

Frances Payne Bolton School of Nursing

Case Western Reserve University Cleveland, Ohio

opinions and off label discussions
Opinions 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 uses

of a commercial product or an investigational use of a

product not yet approved for this purpose

Please consult the full prescribing information before using

any medication mentioned in this program

new electronic evaluation process
New 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
learning objectives cme cne and cpe
Learning Objectives(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
  • 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

CPE

CME/CNE

program overview
Program Overview
  • Treatment challenges/clinical needs
  • New antiviral drugs/formulations
worldwide treatment and prevention gaps 2011
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.

chronic hiv in the us underdiagnosed and undertreated
Chronic HIV in the US:Underdiagnosed and Undertreated

1,106,400-

1,200,000

~80%

Diagnosed

874,056-

960,000

Number (in ‘000s)

~40%

Treated

~20% of All

HIV-Infected

Are HIV RNA

<50 copies/mL

437,028-

489,600

209,773-

376,992

Treated

Diagnosed

Viral Suppression

Prevalence

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.

no single stand alone hiv prevention intervention will halt the hiv pandemic
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
the shift towards earlier initiation of antiretroviral therapy
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
simultaneous use of different classes of prevention strategies
Simultaneous Use of Different Classes of Prevention Strategies

Biomedical

Interventions

Structural

Interventions

HIV Testing,

Linkage to Care,

Expanded ART

Coverage

Combination

HIV

Prevention

Individual and

Small Group

Behavioral

Interventions

Community

Interventions

fda approves first drug for reducing the risk of sexually acquired hiv infection july 16 2012
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.

cdc interim guidance prep in heterosexually active adults and msm
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.

prep trial results
PrEP Trial Results
  • 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)
cdc interim guidance for healthcare providers beginning prep medication regimen
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

CDC. MMWR Morb Mortal Wkly Rep. 2011;60:65-68.

CDC. MMWR Morb Mortal Wkly Rep. 2012;61:586-589.

cdc interim guidance for healthcare providers follow up while on prep
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

CDC. MMWR Morb Mortal Wkly Rep. 2011;60:65-68.

CDC. MMWR Morb Mortal Wkly Rep. 2012;61:586-589.

cdc interim guidance for healthcare providers discontinuing prep
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

CDC. MMWR Morb Mortal Wkly Rep. 2011;60:65-68.

CDC. MMWR Morb Mortal Wkly Rep. 2012;61:586-589.

program overview1
Program Overview
  • Treatment challenges/clinical needs
  • New antiviral drugs/formulations
dhhs guidelines when to start perspectives
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.

when to start treatment
When to Start Treatment

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.

DHHS. Available at: http://www.aidsinfo.nih.gov/ContentFiles/AdultandAdolescentGL.pdf.

Revision February 12, 2013; Thompson MA, et al. JAMA. 2012;308:387-402.

dhhs guidelines preferred regimens
DHHS Guidelines: Preferred Regimens

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.

DHHS. Available at: http://www.aidsinfo.nih.gov/ContentFiles/AdultandAdolescentGL.pdf.

Revision February 12, 2013.

dhhs guidelines alternative regimens
DHHS Guidelines: Alternative Regimens

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.

DHHS. Available at: http://www.aidsinfo.nih.gov/ContentFiles/AdultandAdolescentGL.pdf.

Revision February 12, 2013.

no one right option for everyone limitations of current first line regimens
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
simplified and convenient art achieving goals of therapy
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

DHHS. Available at: http://www.aidsinfo.nih.gov/ContentFiles/AdultandAdolescentGL.pdf.

Revision February 12, 2013.

potential therapeutic targets
Potential Therapeutic Targets

CCR5

Inhibitors

Fusion

Inhibitors

Cytoplasm

Reverse Transcriptase Inhibitors

Protease Inhibitors

Integrase Inhibitors

Nucleus

program overview2
Program Overview
  • Treatment challenges/clinical needs
  • New antiviral drugs/formulations
study 102 quad versus efavirenz emtricitabine tenofovir df
Study 102: QUAD Versus Efavirenz/Emtricitabine/Tenofovir DF

Single-Tablet, Once-Daily Regimens

Phase 3 study

(192 weeks)

Treatment-naïve

Double-blind

HIV RNA >5000 copies/mL

Any CD4 count

Non-inferiority

(12% margin)

Elvitegravir 150 mg/Cobicistat 150 mg/

Emtricitabine/Tenofovir DF (n=348)

Randomization

1:1

Efavirenz 600 mg/

Emtricitabine/Tenofovir DF (n=352)

Primary

Endpoint

Week 48

HIV RNA

<50 Copies/mL

Sax PE, et al. Lancet. 2012;379:2439-2448.

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

study 102 baseline demographics
Study 102:Baseline Demographics

Sax PE, et al. Lancet. 2012;379:2439-2448.

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

study 102 virologic and immunologic outcomes
Study 102:Virologic and Immunologic Outcomes

CD4 Cell Gain

HIV RNA <50 Copies/mL

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

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

Difference (%):

3.6 (-1.6, 8.8)

295

Difference (%):

2.7 (-2.9, 8.3)

273

88%

84%

84%

82%

239*

206

Patients (%)

CD4 Gain (cells/mm3)

96

(n=307/302)

96

(n=348/352)

48

(n=325/315)

48

(n=348/352)

Week

Week

*P=0.009.

Sax PE, et al. Lancet. 2012;379:2439-2448.

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

study 102 virologic outcomes by baseline hiv rna
Study 102: Virologic Outcomesby Baseline HIV RNA

Baseline HIV RNA >100K Copies/mL

Baseline HIV RNA <100K Copies/mL

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

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

90%

86%

85%

84%

83%

82%

81%

81%

Patients (%)

Patients (%)

96

(n=230/236)

96

(n=230/236)

48

(n=348/352)

48

(n=348/352)

Week

Week

Sax PE, et al. Lancet. 2012;379:2439-2448.

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

study 102 week 96 nnrti integrase and nrti resistance
Study 102 (Week 96):NNRTI, Integrase, and NRTI Resistance

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

study 102 week 96 safety and tolerability
Study 102 (Week 96):Safety and Tolerability

Week 96

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

study 103 quad versus atazanavir r emtricitabine tenofovir df
Study 103: QUAD VersusAtazanavir/r + Emtricitabine/Tenofovir DF

Once-Daily Regimens

Phase 3 study

(192 weeks)

Treatment-naïve

Double-blind

HIV RNA >5000 copies/mL

Any CD4 count

Non-inferiority

(12% margin)

Elvitegravir/Cobicistat/

Emtricitabine/Tenofovir DF (n=353)

Randomization

1:1

Atazanavir/r +

Emtricitabine/Tenofovir DF (n=355)

Primary

Endpoint

Week 48

HIV RNA

<50 Copies/mL

DeJesus E, et al. Lancet. 2012;379:2429-2438.

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

study 103 baseline demographics
Study 103:Baseline Demographics

DeJesus E, et al. Lancet. 2012;379:2429-2438.

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

study 103 virologic and immunologic outcomes
Study 103:Virologic and Immunologic Outcomes

CD4 Cell Gain

HIV RNA <50 Copies/mL

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

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

Difference (%):

2.7 (-2.1, 7.5)

Difference (%):

1.1 (-4.5, 6.7)

90%

261

87%

256

83%

82%

211

207

Patients (%)

CD4 Gain (cells/mm3)

96

(n=316/315)

96

(n=353/355)

48

(n=334/321)

48

(n=353/355)

Week

Week

DeJesus E, et al. Lancet. 2012;379:2429-2438.

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

study 103 virologic outcomes by baseline hiv rna
Study 103: Virologic Outcomesby Baseline HIV RNA

Baseline HIV RNA >100K Copies/mL

Baseline HIV RNA <100K Copies/mL

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

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

93%

90%

85%

84%

84%

82%

82%

80%

Patients (%)

Patients (%)

96

(n=150/141)

96

(n=203/214)

48

(n=150/141)

48

(n=203/214)

Week

Week

DeJesus E, et al. Lancet. 2012;379:2429-2438.

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

study 103 week 96 resistance
Study 103 (Week 96):Resistance

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

study 103 week 96 safety and tolerability
Study 103 (Week 96):Safety and Tolerability

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

elvitegravir cobicistat emtricitabine tenofovir df dosing and safety considerations
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.

echo and thrive studies study design 96 weeks
ECHO and THRIVE Studies:Study Design (96 Weeks)

Phase 3 Studies

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

Rilpivirine 25 mg qd +

Emtricitabine/Tenofovir DF qd

Randomization

1:1

ECHO

(n=690)

Efavirenz 600 mg qd +

Emtricitabine/Tenofovir DF qd

Rilpivirine 25 mg qd +

2 NRTIs*

Randomization

1:1

THRIVE

(n=678)

Efavirenz 600 mg qd +

2 NRTIs

Primary endpoint: non-inferiority at week 48 (lower confidence interval <12%).

*Investigator’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.

echo and thrive studies baseline demographics
ECHO and THRIVE Studies:Baseline Demographics

ECHO

THRIVE

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.

echo and thrive studies hiv rna 50 copies ml itt tlovr
ECHO and THRIVE Studies:HIV RNA <50 Copies/mL(ITT-TLOVR)

Rilpivirine

Efavirenz

86%

83%

83%

82%

78%

78%

Patients (%)

CD4

+189

cells/µL

CD4

+171

cells/µL

CD4

+196

cells/µL

CD4

+182

cells/µL

CD4

+228

cells/µL

CD4

+219

cells/µL

ECHO

(n=346/344)

THRIVE

(n=340/338)

Pooled Data

(n=686/682)

Week 48

Week 96

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.

pooled echo thrive post hoc analysis hiv rna 50 copies ml week 96

Rilpivirine

Efavirenz

Rilpivirine

Efavirenz

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

By Baseline HIV RNA

(copies/mL)

By Baseline CD4

(cells/mm3)

85%

84%

81%

80%

79%

79%

75%

75%

71%

70%

69%

56%

HIV RNA <50 Copies/mL (%)

HIV RNA <50 Copies/mL (%)

<50

(n=34/36)

50-<200

(n=194/175)

200-<350

(n=313/307)

>350

(n=144/164)

<100K

(n=368/329)

>100K

(n=318/353)

All patients received emtricitabine/tenofovir DF.

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

pooled echo thrive week 96 discontinuations and virologic failure
Pooled ECHO/THRIVE (Week 96):Discontinuations and Virologic Failure

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

pooled echo thrive week 96 safety
Pooled ECHO/THRIVE (Week 96):Safety

*P<0.0001 and †P=0.0039 versus rilpivirine.

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

echo thrive conclusions
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.

star study design 96 weeks
STAR Study:Design (96 Weeks)

Single-Tablet, Once-Daily Regimens

Phase 3b study

(96 weeks)

Treatment-naïve

Open-label

HIV RNA >2500 copies/mL

Any CD4 count

Genotypic sensitivity

(EFV, FTC, RPV, TDF)

Non-inferiority

(12% margin)

Emtricitabine/Rilpivirine/Tenofovir DF

Once Daily

Randomization

1:1

Efavirenz/Emtricitabine/Tenofovir DF

Once Daily

Primary

Endpoint

Week 48

HIV RNA

<50 Copies/mL

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

star study baseline demographics
STAR Study:Baseline Demographics

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

star study week 48 virologic and immunologic outcomes
STAR Study (Week 48):Virologic and Immunologic Outcomes

HIV RNA <50 Copies/mL

CD4 Cell Gain

Difference (%):

4.1 (-1.1, 9.2)

200

P=0.34

85.8%

191

81.6%

Patients (%)

CD4 Gain (cells/mm3)

EFV/FTC/TDF

(n=392)

EFV/FTC/TDF

(n=392)

FTC/RPV/TDF

(n=394)

FTC/RPV/TDF

(n=394)

Non-inferiority criteria met.

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

star study week 48 virologic outcomes by baseline hiv rna

FTC/RPV/TDF

EFV/FTC/TDF

FTC/RPV/TDF EFV/FTC/TDF

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

HIV RNA <50 Copies/mL)

Virologic Failure

Difference (%):

7.2 (1.1, 13.4)

Difference (%):

-1.8 (-11.1, 7.5)

89%

82%

82%

80%

Patients (%)

Patients (%)

25%

16%

10%

9%

5%

3%

>500K*

(n=36/25)

<100K

(n=260/250)

>100-500K

(n=98/117)

<100K

(n=260/250)

>100K

(n=134/142)

Baseline HIV RNA

Baseline HIV RNA

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

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

emtricitabine rilpivirine tenofovir df dosing and safety considerations
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.

evidence supports combination art for prevention of hiv transmission
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
new electronic evaluation process1
New 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
outcomes measurement reminder
Outcomes 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