Guidelines for the Use of Antiretroviral Agents in
`HIV-l-lnfected Adults and Adolescents
`
`Downloaded from http://aidsinfo.nih.gov/guidelines on 4/7/2015
`
`Visit the AIDSinfo website to access the most up-to-date guideline.
`
`Register for e-mail notification of guideline updates at http://aidsinfo.nih.gov/e-news.
`
`Downloaded from http://aidsinfo.nih.gov/guidelines on 4/7/2015
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`Developed by the HHS Panel on Antiretroviral Guidelines for
`Adults and Adolescents - A Working Group of the
`Office of AIDS Research Advisory Council (OARAC)
`
`How to Cite the Adult and Adolescent Guidelines:
`
`Panel on Antiretroviral Guidelines for Adults and Adolescents. Guidelines for the use of
`antiretroviral agents in HIV-1 -infected adults and adolescents. Department of Health and
`Human Services. Available at I~,’aidsirdo.nih.~’Con~nt~:iies~.dul~au~1
`,’~’.,~.~.~C.~.O!~."..-.~#~i.[. Section accessed [insert date] [insert page number, table number, etc.,
`if applicable]
`
`It is emphasized that concepts relevant to HIV management evolve rapidly. The Panel has a
`mechanism to update recommendations on a regular basis, and the most recent informa-
`tion is available on the AIDSinfo website
`
`Access AI DSinfo
`mobile site
`
`Downloaded from .h..Rp~:..//..a..i..d...s.Ln..f..~...~.n..i..h....g.~...v../g.u.i..d..e..~.Ln..e.~.s. on 4/17/12D:t 014
`
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`This interim revision of the Guidelines includes a revised section on Hepatitis C Virus (HCV)/H1V
`Coinfection, with emphasis on considerations for use of antiretroviral (ARV) drugs in patients who also
`receive treatment for HCV infection. A new table (Table 12) provides clinicians with guidance on the
`concomitant use of HCV drugs and ARV drugs, with a focus on potential pharmacokinetic drug interactions.
`The Panel refers clinicians to http://www.hcv2~uidelines.org for guidance on the diagnosis and treatment of
`HCV infections.
`
`Guidelines for the Use of Antiretroviral Agents in HIV- I-Infected Adults and Adolescents
`
`Downloaded from .h...t~.tp.~]../~.a.i~.d..s..i..n...f..~.:~.n..i..h..:g.~.~.v../.g~..~i..d..e..~j..n...e..s. on 4/7/2015
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`Lupin Ex. 1067 (Page 3 of 282)
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`Table of Contents
`
`What’s New in the Guidelines ....................................................................................................................... i
`
`Panel Roster ......................................................................................................................................................... vi
`
`Financial Disclosure ..................................................................................................................................... viii
`
`Introduction ...................................................................................................................................................... A- 1
`Table 1. Outline of the Guidelines Development Process .................................................................. A-2
`
`Table 2. Rating Sehemej’br Recommendations ................................................................................... A-3
`
`Baseline Evaluation ...................................................................................................................................... 13-1
`
`Laboratory Testing ......................................................................................................................................... c-1
`Laboratory Testing for initial Assessment and Monitoring While on Antiretroviral Therapy .............. C- 1
`Table 3. LaboratoJT Monitoring Sehedulej’br Patients Bejbre and Aj?er initiation of
`Antiretroviral Therapy ..................................................................................................................... C-2
`
`Plasma H1V- 1 RNA (Viral Load) and CD4 Count Monitoring ............................................................. C-5
`
`Table 4. Recommendations on the indications and Frequency of Viral Load and
`CD4 Count Monitoring .................................................................................................................... C-8
`
`Drug-Resistance Testing ...................................................................................................................... C- 11
`
`Table 5. Recommendations.ibr Using DJ7tg-Resistance Assays .................................................... C- 15
`
`Co-Receptor Tropism Assays ............................................................................................................... C-20
`
`HLA-B*5701 Screening ...................................................................................................................... C-23
`
`Treatment Goals .............................................................................................................................................. D-1
`
`Initiating Antiretroviral Therapy in Treatment-Naive Patients ................................................ E- 1
`
`What to Start ..................................................................................................................................................... F-1
`
`Table 6~ Recommended and Alternative Antiretroviral Regimen Options jbr
`Treatment-Naive Patients ................................................................................................................. F-7
`
`Table Z Advantages and Disadvantages of Antiretroviral Components Recommended
`as initial Antiretroviral Therapy .................................................................................................... F-22
`
`Table 8. Antiretroviral Components or Regimens Not Recommended as initial Therapy ............. F-25
`
`WhatNot to Use .............................................................................................................................................. G-1
`
`Table 9. Antiretroviral Regimens or Components That Should Not Be Q[’i~red At Any Time ......... G-3
`
`Management of the Treatment-Experienced Patient .................................................................... H-1
`Virologic Failure and Suboptimal immunologic Response ................................................................... H-1
`
`Regimen Switching in the Setting of Virologic Suppression .............................................................. H-13
`
`Exposure-Response Relationship and Therapeutic Drug Monitoring (TDM) for Antiretroviral Agents ...H-17
`
`Table 10a. Trough Concentrations of Antiretroviral Drugs j’br Patients Who Have
`D~7tg-Susceptible Vi~7ts .................................................................................................................. H-19
`
`Guidelines for the Use of Antiretroviral Agents in HIV- I-Infected Adults and Adolescents
`
`Downloaded from .h-t..tp.]../..a.i..d..s.~t.n-f..Q:..n.[t.h..:g.~...v../.g~..j..d..e..~j..n-e..s. on 4/7/2015
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`Table 10b. Trough Concentrations of A ntiretroviral Drugs jbr Treatment-Experienced
`Patients with Virologic Failure ..................................................................................................... H-20
`
`Discontinuation or interruption of Antiretroviral Therapy .................................................................. H-21
`
`Considerations,[br Antiretroviral Use in Special Patient Populations ................................... I- 1
`Acute and Recent (Early) H1V infection ................................................................................................. 1-1
`
`Table 11. ldentijj;ing, Diagnosing, and Managing Acute and Recent H1V-1 lq/bction ..................... 1-5
`
`H1V-infected Adolescents and Young Adults .......................................................................................... 1-8
`
`H1V and illicit Drug Users .................................................................................................................... 1-14
`
`H1V-infected Women ............................................................................................................................ 1-18
`
`H1V-2 infection ..................................................................................................................................... 1-25
`
`H1V and the Older Patient ..................................................................................................................... 1-28
`
`Considerations,[br A ntiretroviral Use in Patients with Coinfections ...................................... J- 1
`Hepatitis B (HBV)/H1V Coinfection ...................................................................................................... J- 1
`
`Hepatitis C (HCV)/H1V Coinfection ...................................................................................................... 1-5
`
`Table 12. Recommendations jbr Concomitant Use of Selected Antiretroviral DlT~gs and All
`Food and Drug Administration (FDA)-Approved Di7~gs jbr Treatment of Hepatitis C in
`HI V-l~/bcted A dults .......................................................................................................................... J-9
`
`Mycobacterium Tuberculosis Disease with H1V Coinfection ............................................................... J-14
`
`Limitations to Treatment Safe& and E.[]icacy ..................................................................................
`Adherence to Antiretroviral Therapy .......................................................................................................... K-1
`
`Table 13. Strategies to improve Adherence to Antiretroviral Therapy and Rentention in Care .....K-4
`
`Adverse Effects of Antiretroviral Agents .............................................................................................. K-8
`
`Table 14. Antiretroviral Therapy-Associated Common and/or Severe Adverse Ef/bcts .................. K-9
`
`Table 15. Antiretroviral Therapy-Associated Adverse Events That Can Be Managed with
`Substitution of Alternative A ntiretroviral Agent ............................................................................ K- 17
`
`Cost Considerations and Antiretroviral Therapy ................................................................................. K-21
`
`Table l & Monthly Average Wholesale Price of Antiretroviral D~7~gs ........................................... K-22
`
`Drug Interactions ........................................................................................................................................... L- 1
`Table 17. D~gs That Should Not Be Used With Antiretroviral Agents .......................................... L-4
`
`Table 18a. D~7~g interactions between Protease lnhibitors and Other D~7~gs ................................ L-6
`
`Table 18b. Di7~g interactions between Non-Nucleoside Reverse Transcriptase lnhibitors and
`Other D~7tgs ................................................................................................................................... L- 18
`
`Table 18c. D~7~g interactions between Nucleoside Reverse Transcriptase lnhib#ors and Other
`D~7~gs (including Antiretroviral Agents) ........................................................................................ L-25
`
`Table 18d. D~7~g interactions between lntegrase Strand Tran~/~r lnhibitors and Other D~7~gs ..L-27
`
`Table 1Be. D~7~g interactions between CCR5 Antagonist and Other D~7~gs .................................. L-35
`
`Table 19a. interactions between Non-Nucleoside Reverse Transcriptase lnhibitors, and
`Protease lnhibitors ......................................................................................................................... L-37
`
`Table 19b. interactions between lntegrase Strand Tran~/br lnhibitors and
`
`Guidelines for the Use of Antiretroviral Agents in HIV- I-Infected Adults and Adolescents
`
`Downloaded from .h-t..tp.]../..a.i..d..s.2t.n-f..~.:..n.[t.h..:g.~...v../.g~...i..d..e..~j..n-e..s. on 4/7/2015
`
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`Non-Nucleoside Reverse Transcriptase lnhibitors or Protease lnhibitors .................................... L-39
`
`Preventing Secondary Transmission of HIV .................................................................................... M-1
`
`Conclusion ......................................................................................................................................................... N-1
`
`Appendix A: Key to Acronyms .................................................................................................................. o- 1
`
`Appendix B: Drug Characteristics Tables ........................................................................................... P-1
`Appendix B, Table 1. Characteristics of Nucleoside Reverse Transcriptase lnhibitors ......................... P-1
`
`Appendix B, Table 2. Characteristics of Non-Nucleoside Reverse Transcriptase lnhibitors ................. P-6
`
`Appendix B, Table 3. Characteristics of Protec~e lnhibitors ................................................................. P-8
`
`Appendix B, Table 4. Characteristics of lntegrase lnhibitors .............................................................. P-13
`
`Appendix B, Table 5. Characteristics of Fusion inhibitor ................................................................... P-14
`
`Appendix B, Table 6~ Characteristics of CCR5 Antagonist .................................................................. P-14
`
`Appendix B, Table Z Antiretroviral Dosing Recommendations in Patients with Renal or
`Hepatic lnm(/j%iency ............................................................................................................................ P- 15
`
`List of Tables
`Table 1. Outline of the Guidelines Development Process ........................................................................ A-2
`
`Table 2. Rating Scheme for Reconm~endations ......................................................................................... A-3
`
`Table 3. Laborato~ Monitoring Schedule for Patients Before and After initiation of
`Antiretroviral Therapy ........................................................................................................................... C-2
`
`Table 4. Recommendations on the indications and Frequency of Viral Load and
`CD4 Count Monitoring .......................................................................................................................... C-8
`
`Table 5. Recommendations for U sing Drng-Resistance Assays .......................................................... C- 15
`
`Table 6. Recommended and Alternative Antiretroviral Regimen Options for
`Treatment-Naive Patients ....................................................................................................................... F-7
`
`Table 7. Advantages and Disadvantages of Antiretroviral Components Reconm~ended as
`Initial Antiretroviral Therapy ............................................................................................................... F-22
`
`Table 8. Antiretroviral Components or Regimens Not Recommended as Initial Therapy ................... F-25
`
`Table 9. Antiretroviral Regin~ens or Components That Should Not Be Offered At Any Time ............. G-3
`
`Table 10a. Trough Concentrations of Antiretroviral Drugs for Patients Who Have
`Drug-Susceptible Virus ........................................................................................................................ H- 19
`
`Table 10b. Trough Concentrations of Antiretroviral Drugs for Treatment-Experienced Patients
`with Virologic Failure .......................................................................................................................... H-20
`
`Table 11. identifying, Diagnosing, and Managing Acute and Recent H1V-1 infection .......................... 1-5
`
`Table 12. Reconm~endations for Concomitant Use of Selected Antiretroviral Drugs and All
`Food and Drug Administration (FDA)-Approved Drugs for Treatment of Hepatitis C in
`H1V-lnfected Adults ................................................................................................................................ J-9
`
`Table 13. Strategies to lmprove Adherence to Antiretroviral Therapy .................................................. K-4
`
`Table 14. Antiretroviral Therapy-Associated Common and/or Severe Adverse Effects ....................... K-9
`
`Table 15. Antiretroviral Therapy-Associated Adverse Events That Can Be Managed with
`
`Guidelines for the Use of Antiretroviral Agents in HIV- I-Infected Adults and Adolescents
`
`iv
`
`Downloaded from .h...t..tp.]../..a.i..d..s.2t.n...f..~.:..n.[t.h..:g.~...v../.g~...i..d..e..~j..n...e..s. on 4/7/2015
`
`Lupin Ex. 1067 (Page 6 of 282)
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`S ubstitution of Alternative Antiretroviral Agent ................................................................................ K- 17
`
`Table 16. Monthly Average Wholesale Price of Antiretroviral Drugs ................................................ K-22
`
`Table 17. Drugs That Should Not Be Used With Antiretroviral Agents ................................................ L-4
`
`Table 18a. Drug interactions between Protease lnhibitors and Other Drugs ......................................... L-6
`
`Table 18b. Drug interactions between Non-Nucleoside Reverse Transcriptase lnhibitors and
`Other Drugs .......................................................................................................................................... L- 18
`
`Table 18c. Drug interactions between N ucleoside Reverse Transcriptase lnhibitors and
`Other Drugs (including Antiretroviral Agents) .................................................................................... L-25
`
`Table 18d. Drug interactions between lntegrase Strand Transfer lnhibitors and Other Drugs ........... L-27
`
`Table 18e. Drug interactions between CCR5 Antagonist and Other Drugs ......................................... L-35
`
`Table 19a. Interactions bet~veen Non-Nucleoside Reverse Transcriptase lnhibitors, and
`Protease lnhibitors ................................................................................................................................ L-37
`
`Table 19b. interactions between lntegrase Strand Transfer lnhibitors and
`Non-Nucleoside Reverse Transcriptase lnhibitors or Protease lnhibitors ........................................... L-39
`
`Guidelines for the Use of Antiretroviral Agents in HIV- I-Infected Adults and Adolescents
`
`Downloaded from .h...t..tp..]../..a.i..d..s.~t.n...f..~.:..n.j..h..:g.~...v../.g~...i..d..e..~j..n...e..s. on 4/7/2015
`
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`

`These Guidelines j’br the Use of Antiretroviral Agents in H1V-l-l~iOcted Adults and Adolescents are developed
`by the Department of Health and Human Services (HHS) Panel on Antiretroviral Guidelines for Adults and
`Adolescents (the Panel) a Wofidng Group of the Office of A1DS Research Advisory Council (OARAC).
`
`Panel Co-Chairs
`Roy M. Gulick
`Martin S. Hirsch
`H. Clifford Lane
`
`Executive Secretary
`Alice K. Pau
`
`Scientific Members
`J udith Aberg
`Adaora Adimora
`John T. Brooks
`J. Kevin Carrnichael
`Deborah L. Cohan
`Efic Daar
`Gerald Ffiedland
`Rajesh T. Gandhi
`Stephen J. Gange
`Thomas Giordano
`Richard Haubrich
`Michael D. Hughes
`Peter Hunt
`Bill G. Kapogiarmis
`Mafia Keller
`Daniel R. Kuritzkes
`Jeffrey Lennox
`Richard W. Price
`James Raper
`Bret J. Rudy
`Paul Sax
`Kimbefiy Scarsi
`Mark Sulkowski
`Pablo Tebas
`
`Weill Medical College of Cornell University, New York, NY
`Massachusetts General Hospital and Harvard Medical School, Boston, MA
`
`National institutes of Health, Bethesda, MD
`
`National institutes of Health, Bethesda, MD
`
`lcahn School of Medicine of Mount Sinai University, New York, NY
`University of North Carolina, Chapel Hill, NC
`Centers for Disease Control and Prevention, Atlanta, GA
`E1 Rio Specialty immunology Associates, Tucson, AZ
`University of Californi~San Francisco, San Francisco, CA
`University of California Los Angeles, Harbor-UCLA Medical Center, Los Angeles, CA
`Yale University School of Medicine, New Haven, CT
`Massachusetts General Hospital and Harvard Medical School, Boston, MD
`Johns Hopkins University, Baltimore, MD
`Baylor College of Medicine, Houston, TX
`University of Californi~San Diego, San Diego, CA
`Harvard School of Public Health, Boston, MA
`University of Californi~San Francisco, San Francisco, CA
`National institutes of Health, Bethesda, MD
`Albert Einstein College of Medicine, New York, NY
`Brigham and Women’s Hospital and Hm-vard Medical School, Boston, MA
`Emory University, Atlanta, GA
`University of Californi~San Francisco, San Francisco, CA
`University of Alabama at Birmingham, Birmingham, AL
`New York University, New York, NY
`Brigham and Women’s Hospital and Hm-vard Medical School, Boston, MA
`University of Nebraska, Omaha, NE
`Johns Hopkins University, Baltimore, MD
`University of Pennsylvania, Philadelphia, PA
`
`Zelalem Temesgen
`
`Mayo Clinic, Rochester, MN
`
`Phyllis Tien
`
`University of Californi~San Francisco, San Francisco, CA
`
`Guidelines for the Use of Antiretroviral Agents in HIV- I-Infected Adults and Adolescents
`
`Downloaded from .h-t..tp..]../~.a.i~.d..s.2t.n-f..~.:~.n.2t.h..:g.~.~.v../.g~...i..d..e..~j..n-e..s. on 4/7/2015
`
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`

`Rochelle Walensky
`David A. Wohl
`
`Massachusetts General Hospital and Harvard Medical School, Boston, MA
`University of North Carolina, Chapel Hill, NC
`
`Community Members
`Lei Chou
`Treatment Action Group, New York, NY
`David Evans
`Project inform, San Francisco, CA
`Danielle Houston
`Houston, TX
`A1DS Treatment Activists Coalition, Palm Springs, CA
`Jeff Taylor
`Program for Wellness Restoration, Houston, TX
`Nelson Vergel
`
`Members Representing Department of Health and Human Services Agencies
`Victoria Cargill
`National institutes of Health, Rockville, MD
`Laura Cheever
`Health Resources and Services Administration, Rockville, MD
`Rohan Hazra
`Nat~on~ In~itutes ~e~th; Bethesdai MD
`Jonathan Kaplan
`Centers for Disease Control and Prevention, Atlanta, GA
`Kendall Marcus
`Food and Drug Administration, Silver Spring, MD
`Henry Masur
`National institutes of Health, Bethesda, MD
`Lyrme Mofenson
`National institutes of Health, Bethesda, MD
`Kimberly Struble
`Food and Drug Administration, Silver Spring, MD
`
`Guidelines for the Use of Antiretroviral Agents in HIV- I-Infected Adults and Adolescents
`
`vii
`
`Downloaded from .h...t..tp.]../..a.i..d..s..i..n...f..~.:..n..i..h..:g.~...v../.g~...i..d..e..~j..n...e..s. on 4/7/2015
`
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`

`HHS Panel on Antiretroviral Guidelines for Adults and
`Adolescents Financial Disclosure (Reporting Period: February 2013-
`February 2014) (page 1 of 3)
`
`Judith Aberg
`
`Adaora Adimora
`
`John T. Brooks
`
`Victoria Ann Cargill
`
`Kevin Carmichael
`
`Laura W. Cheever
`
`Lei Chou
`
`Deborah Cohan
`
`Eric Daar
`
`David Evans
`
`Gerald H. Fdedland
`
`Rajesh Gandhi
`
`Stephen Gange
`
`Thomas Giordano
`
`Roy Gulick
`
`Richard Haubrich
`
`M
`
`U
`
`U
`
`U
`
`U
`
`U
`
`U
`
`U
`
`U
`
`M
`
`U
`
`M
`
`M
`
`M
`
`C
`
`M
`
`¯ Abbvie
`¯ Janssen
`¯ Merck
`
`None
`
`None
`
`None
`
`None
`
`None
`
`None
`
`None
`
`¯ Abbvie
`¯ Bristol-Myers Squibb
`¯ Gilead
`¯ Janssen Therapeutics
`¯ Merck
`¯ Teva
`¯ ViiV
`
`¯ Bristol-Myers Squibb
`¯ Gilead
`¯ ViiV
`
`¯ Bristol-Myers Squibb
`¯ Gilead
`
`¯ Janssen
`¯ ViiV/Abbott
`
`Merck
`
`None
`
`None
`
`¯ Abbvie
`¯ Bristol-Myers Squibb
`¯ Gilead
`
`¯ GlaxoSmithKline/PfizerNiiV
`¯ Janssen
`¯ Merck
`
`Advisory Board
`¯ Advisory Board
`¯ Advisory Board
`
`N/A
`
`N/A
`
`N/A
`
`N/A
`
`N/A
`
`N/A
`
`N/A
`
`Advisory Board
`¯ Consultant; Research support
`¯ Advisory Board; Research support
`Advisory Board
`¯ Consultant; Research support
`¯ Consultant
`¯ Consultant; Research support
`
`Advisory Board
`Advisory Board
`¯ Advisory Board; Travel support
`
`Research support
`Research support
`
`Educational program support
`Educational program support
`
`DSMB member
`
`N/A
`
`N/A
`
`Research support
`Advisory Board; Research support
`¯ Advisory Board; Research support;
`Speakers Bureau (ended 12/2013);
`Travel support
`Research support
`¯ Advisory Board; Travel support
`Advisory Board; Research support
`
`Martin Hirsch
`
`C
`
`None
`
`N/A
`
`Guidelines for the Use of Antiretroviral Agents in HIV- I-Infected Adults and Adolescents
`
`viii
`
`Downloaded from .h...t..tp..]../~.a.i~.d..s.~t.n...f..~.:~.n.~t.h..:g.~.~.v../.g~...i..d..e..~j..n...e..s. on 4/7/2015
`
`Lupin Ex. 1067 (Page 10 of 282)
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`

`

`HHS Panel on Antiretroviral Guidelines for Adults and
`Adolescents Financial Disclosure (Reporting Period: February 2013-
`February 2014) (page 2 of 3)
`
`Danielle Houston
`
`Michael D. Hughes
`
`Peter W. Hunt
`
`M
`
`M
`
`U
`
`Daniel R. Kudtzkes
`
`U
`
`i Gilead
`
`i None
`Bristol-Myers Squibb
`Gilead
`GlaxoSmithKline
`Merck
`Salix
`Tobira
`
`Bristol-Myers Squibb
`Celera
`Gilead
`GlaxoSmithKline
`InnoVirvax
`Merck
`Tobira
`ViiV
`
`Honorada
`
`N/A
`
`Consultant
`Honorada; Consultant
`Travel support
`Advisory Board; Consultant
`Research support
`Consultant
`
`Consultant
`Consultant
`Consultant
`Consultant
`Consultant
`Consultant; Grant support
`Consultant
`Consultant; Speaking honorarium
`
`James Raper
`
`Brett Rudy
`
`Paul E. Sax
`
`Kimberly Scarsi
`
`Kimbedy
`
`Struble
`
`M
`
`M
`
`M
`
`U
`
`M
`
`None
`
`None
`
`¯ Abbvie
`i ° Bristol-Myers Squibb
`i ° Gilead
`i ° Janssen Therapeutics
`i ° Merck
`i ° ViiV
`
`i None
`
`i None
`
`N/A
`
`N/A
`
`Consultant
`Advisory Board; Research support
`Advisory Board; Research support
`Consultant
`Advisory Board
`Advisory Board; Research support
`
`N/A
`
`N/A
`
`Guidelines for the Use of Antiretroviral Agents in HIV- I-Infected Adults and Adolescents
`
`Downloaded from h.t..tp..;/../..a.i..d..s..i..n...f..~.:..n..i..h..:g.~.~.v../.g~...i..d..e..~j..n...e..s, on 4/7/2015
`
`Lupin Ex. 1067 (Page 11 of 282)
`
`

`

`HHS Panel on Antiretroviral Guidelines for Adults and
`Adolescents Financial Disclosure (Reporting Period: February 2013-
`February 2014) (page 3 of 3)
`
`Mark Sulkowski
`
`Jeff Taylor
`
`Pablo Tebas
`
`Zelalem Temesgen
`
`Phyllis
`
`Nelson R. Vergel
`
`¯ Abbvie
`¯ Bayer HealthCare
`¯ Boehringer Ingelheim
`¯ Bristol-Myers Squibb
`¯ Gilead
`
`¯ Idenix Inc
`¯ Janssen Therapeutics
`¯ Merck
`¯ Pfizer
`¯ Vertex
`
`i BMS
`
`i ¯ Astra Zeneca
`i ¯ Gilead
`i ¯ GlaxoSmithKline
`i ¯ Merck
`
`i ¯ Gilead
`i ¯ Janssen Therapeutics
`i ¯ Merck
`i ¯ Pfizer
`i ¯ ViiV
`i ¯ Bristol-Myers Squibb
`
`i None
`
`M
`
`U
`
`M
`
`U
`
`M
`
`Advisory Board; Research support
`Advisory Board; Research support
`Advisory Board; Research support
`Advisory Board; Research support
`Advisory Board; DSMB member;
`Research support
`¯ Advisory Board
`Advisory Board; Research support
`Advisory Board; Research support
`Steedng committee
`Advisory Board; Research support
`
`i ¯ Consultant
`
`i ¯ Consultant
`i ¯ Consultant
`i ¯ Adjudication committee member
`i ¯ Consultant
`Education grant; Research support
`Education grant
`Education grant
`Reseamh support
`Education grant
`
`¯ Advisory Board
`
`N/A
`
`N/A
`U
`Rochelle Walensky
`i None
`....................................................... ~ .................................... ~ ......................................................................... * ..................................................................
`David Alain Wohl
`U
`Advisory Board; Research support
`i ¯ Gilead
`¯ Advisory Board
`i ¯ Janssen Therapeutics
`Research support
`i ¯ Merck
`Research support
`i ¯ ViiV
`
`Key to Abbreviations: C = Co-Chair; DSMB = Data Safety Monitodng Board; ES = Executive Secretary; M = Member; N/A = Not
`Applicable
`
`Guidelines for the Use of Antiretroviral Agents in HIV- I-Infected Adults and Adolescents
`
`x
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`Lupin Ex. 1067 (Page 12 of 282)
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`Introd uction (Last updated February 12, 2013; last reviewed February 12, 2013)
`
`Antiretroviral therapy (ART) for the treatment of H1V infection has improved steadily since the advent of
`potent combination therapy in 1996. New drugs that offer new mechanisms of action, improvements in
`potency and activity even against multidrug-resistant viruses, dosing convenience, and tolerability have been
`approved. ART has dramatically reduced H1V-associated morbidity and mortality and has transformed H1V
`disease into a chronic, manageable condition, in addition, effective treatment of H1V-infected individuals
`with ART is highly effective at preventing transmission to sexual partners] However, less than one-third of
`H1V-infected individuals in the United States have suppressed viral loads,~- which is mostly a result of
`undiagnosed H1V infection and failure to link or retain diagnosed patients in care. Despite remarkable
`improvements in H1V treatment and prevention, economic and social ban51ers that result in continued
`morbidity, mortality, and new H1V infections persist.
`
`The Department of Health and Human Services (HHS) Panel on Antiretroviral Guidelines for Adults and
`Adolescents (the Panel) is a working group of the Office of A1DS Research Advisory Council (OARAC).
`The primary goal of the Panel is to provide H1V care practitioners with recommendations based on current
`knowledge of antiretroviral (ARV) drugs used to treat adults and adolescents with H1V infection in the
`United States. The Panel reviews new evidence and updates recommendations in these guidelines when
`needed. The Panel’s primary areas of attention have included baseline assessment, treatment goals,
`indications for initiation of ART, choice of the initial regin~en for ART-naive patients, drugs or combinations
`to avoid, management of adverse effects and drug interactions, management of treatment IMlure, and special
`ART-related considerations in specific patient populations. For reconm~endations related to pre-exposure
`H1V prophylaxis (PREP) for H1V-uninfected persons, please refer to recommendations from the Centers for
`Disease Control and Prevention (CDC).3, 4
`
`These guidelines generally represent the state of knowledge regarding the use of ARV agents. However,
`because the science of H1V evolves rapidly, the availability of new agents and new clinical data may change
`therapeutic options and preferences, information included in these guidelines may not be consistent with
`approved labeling for the particular products or indications in question, and the use of the terms "safe" and
`"effective" may not be synonymous with the Food and Drug Administration (FDA)-defined legal standards
`for product approval. The Panel frequently updates the guidelines (current and archived versions of the
`guidelines are available on the A1DSinjb website at h_~p://www.aidsinfo.nih, og~). However, the guidelines
`carmot always be updated apace with the rapid evolution of new data in the field of H1V and cannot offer
`guidance on care for all patients. Clinicians should exercise clinical j udgment in management decisions
`tailored to unique patient circumstances.
`
`The Panel recognizes the importance of clinical research in generating evidence to address unanswered
`questions related to the optimal safety and efficacy of ART. The Panel encourages both the development of
`protocols and patient participation in well-designed, institutional Review Board (1RB)-approved clinical
`trials.
`
`Guidelines for the Use of Antiretroviral Agents in HIV- I-Infected Adults and Adolescents
`
`A-1
`
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`Lupin Ex. 1067 (Page 13 of 282)
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`Guidelines Development Process
`
`Table 1. Outline of the Guidelines Development Process
`
`Goal of the
`guidelines
`
`Panel members
`
`Financial
`disclosure
`
`Users of the
`guidelines
`
`Developer
`
`Provide guidance to HIV care practitioners on the optimal use of antiretroviral (ARV) agents for the treatment of
`HIV infection in adults and adolescents in the United States.
`
`The Panel is composed of approximately 40 voting members who have expertise in HIV care and research. The
`Panel includes at least one representative from each of the following U.S. Department of Health and Human Services
`(HHS) agencies: Centers for Disease Control and Prevention (CDC), Food and Drag Administration (FDA), Health
`Resource Services Administration (HRSA), and National Institutes of Health (NI H). Approximately two-thirds of the
`Panel members are non-governmental scientific members. The Panel also includes four to five community members
`with knowledge in HIV treatment and care. The U.S. government representatives are appointed by their respective
`agencies; other Panel members are selected after an open announcement to call for nominations. Each member
`serves on the Panel for a 4-year tem~ with an option for reappointment for an additional te