Treatment for Adult HIV Infection

2004 Recommendations of the International AIDS Society-USA Panel

Yeni, Patrick G. MD
Hammer, Scott M. MD
Hirsch, Martin S. MD
Saag, Michael S. MD
Schechter, Mauro MD, PhD
Carpenter, Charles C. J. MD
Fischl, Margaret A. MD
Gatell, Jose M. MD, PhD
Gazzard, Brian G. MA, MD
Jacobsen, Donna M. BS
Katzenstein, David A. MD
Montaner, Julio S. G. MD
Richman, Douglas D. MD
Schooley, Robert T. MD
Thompson, Melanie A. MD
Vella, Stefano MD
Volberding, Paul A. MD

Department of Infectious Diseases, Hôpital Bichat-Claude Bernard, X. Bichat Medical School, Paris, France (Dr Yeni); Department of Medicine, Columbia University College of Physicians and Surgeons, New York, NY (Dr Hammer); Department of Immunology and Infectious Diseases, Harvard Medical School, Boston, Mass (Dr Hirsch); Department of Medicine, University of Alabama, Birmingham (Dr Saag); Department of Preventive Medicine, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brasil (Dr Schechter); Department of Biomedicine, Brown University School of Medicine, Providence, RI (Dr Carpenter); Department of Medicine, University of Miami School of Medicine, Miami, Fla (Dr Fischl); Department of Medicine, University of Barcelona, Barcelona, Spain (Dr Gatell); Department of HIV Medicine, Chelsea and Westminster Hospital, London, England (Dr Gazzard); International AIDS Society-USA, San Francisco, Calif (Ms Jacobsen); Department of Medicine, Stanford University Medical Center, Stanford, Calif (Dr Katzenstein); Department of Medicine, University of British Columbia, Vancouver (Dr Montaner); Departments of Pathology and Medicine, University of California and San Diego VA Healthcare System, San Diego (Dr Richman); Department of Medicine, University of Colorado School of Medicine, Denver (Dr Schooley); AIDS Research Consortium of Atlanta, Ga (Dr Thompson); Istituto Superiore di Sanità, Rome, Italy (Dr Vella); Department of Medicine, University of California and San Francisco Veterans Affairs Medical Center, San Francisco (Dr Volberding).

Corresponding Author: Patrick G. Yeni, MD, Hôpital Bichat-Claude Bernard, 46 Rue Henri-Huchard, 75877 Paris Cedex 18, France ([email protected]).

Financial Disclosures Dr Yeni has received research grants for site investigator from GlaxoSmithKline, Bristol-Myers Squibb, Boehringer Ingelheim, Roche, Tibotec/Virco, and Gilead. Dr Hammer has received research grants for site investigator from Roche, GlaxoSmithKline, and Merck. Dr Hirsch has received research support from Takeda. Dr Saag has received research support from Abbott Laboratories, Bristol-Myers Squibb, Gilead Sciences, GlaxoSmithKline, Ortho Biotech/Johnson & Johnson, Pfizer/Agouron, and Hoffmann-LaRoche. Dr Fischl has received research grants from Abbott Laboratories, Bristol-Myers Squibb, Gilead Sciences, GlaxoSmithKline, and Ortho Biotech. Dr Gazzard has received research grants from Abbott Laboratories, Boehringer Ingelheim, Pfizer, GlaxoSmithKline, Bristol-Myers Squibb, and Johnson & Johnson. Dr Montaner has received grants from Abbott Laboratories, Agouron Pharmaceuticals, Shire Biochemical, Boehringer Ingelheim, Bristol-Myers Squibb, DuPont Pharma, Gilead Sciences, GlaxoSmithKline, Roche, Kucera Pharmaceutical, Merck Frosst Laboratories, Pharmacia & Upjohn, and Trimeris. Dr Schooley has received grants from GlaxoSmithKline, Bristol-Myers Squibb, Merck, and Tibotec/Virco. Dr Thompson has received grants from Abbott Laboratories, Agouron/Pfizer Pharmaceuticals, Boeringer Ingelheim, Bristol-Myers Squibb, Chiron Corporation, GlaxoSmithKline, Gilead Sciences, Merck Research Laboratories, Oxo-Chemie, Roche, Serono, Theratechnologies, Triangle Pharmaceuticals, Trimeris, and VaxGen.

Dr Yeni has received honoraria for advisory positions and lecture sponsorships from Abbott Laboratories, Bristol-Myers Squibb, Boehringer Ingelheim, Roche, Tibotec/Virco, and Merck Sharp and Dohme. Dr Saag has received honoraria for positions on the speakers bureau for Abbott Laboratories, Boeringer Ingelheim, Bristol-Myers Squibb, Gilead Sciences, GlaxoSmithKline, OrthoBiotech, Johnson & Johnson, Pfizer, Agouron, Roche, Schering-Plough, Shire Pharmaceutical, TherapyEdge, Tibotec/Virco, Trimeria, Vertex, and ViroLogic. Dr Schechter has received honoraria from Abbott Laboratories, Bristol-Myers Squibb, GlaxoSmithKline, Merck, and Roche. Dr Fischl has received honoraria for continuing medical education programs from GlaxoSmithKline. Dr Gatell has served in advisory positions for Roche, Bristol-Myers Squibb, Merck Sharp and Dohme, GlaxoSmithKline, Gilead, Boehringer Ingelheim, Abbott Laboratories, Tibotec/Virco. Dr Gazzard has received lectureship fees from Abbott Laboratories, Boehringer Ingelheim, Pfizer, GlaxoSmithKline, Bristol-Myers Squibb, and Johnson & Johnson. Dr Katzenstein has held advisory positions at Boehringer Ingelheim, Bristol-Myers Squibb, Gilead Sciences, GlaxoSmithKline, Merck, ViroLogic, Visible Genetics, and the Doris Duke Charitable Trust. Dr Montaner has received honoraria for speaking from Abbott Laboratories, Agouron Pharmaceuticals, Shire Biochemical, Boehringer Ingelheim, Bristol-Myers Squibb, DuPont Pharma, Gilead Sciences, GlaxoSmithKline, Hoffmann-La Roche, Kucera Pharmaceutical, Merck Frosst Laboratories, Pharmacia & Upjohn, and Trimeris Inc. Dr Thompson has received honoraria for lecture sponsorships and continuing medical education from Abbott Laboratories, Agouron/Pfizer Pharmaceuticals, Boeringer Ingleheim, Bristol-Myers Squibb, GlaxoSmithKline, Gilead Sciences, Roche, Serono, Triangle Pharmaceuticals, and Trimeris. Dr Vella has received lecture sponsorship for satellite symposia and continuing medical education programs from Merck, Agouron, Gilead, Boehringer Ingelheim, and Roche. Dr Volberding has received honoraria from Gilead, Bristol-Myers Squibb, GlaxoSmithKline, and Boehringer Ingelheim.

Dr Hammer has been a consultant for Bristol-Myers Squibb, GlaxoSmithKline, Merck, Shionogi, Pfizer, Boehringer Ingelheim, Shire, Gilead, and Tibotec/Virco. Dr Hirsch has been a consultant for Schering Plough, GlaxoSmithKline, and Bristol-Myers Squibb. Dr Saag has been a consultant for Abbott Laboratories, Boeringer Ingelheim, Bristol-Myers Squibb, Gilead Sciences, GlaxoSmithKline, OrthoBiotech/Johnson & Johnson, Pfizer/Agouron, Roche, Schering-Plough, Shire Pharmaceutical, TherapyEdge, Tibotec/Virco, Trimeria, Vertex, and ViroLogic. Dr Schechter has been a consultant for Abbott Laboratories, Bristol-Myers Squibb, GlaxoSmithKline, Merck, and Roche. Dr Fischl has served as an advisor for Agouron Pharmaceuticals and GlaxoSmithKline. Dr Richman has been a consultant for Abbott Laboratories, Bristol-Myers Squibb, Chiron, Gilead, GlaxoSmithKline, Merck, Novirio, Pfizer, Roche, Takeda, Triangle, and ViroLogic. Dr Schooley has been a consultant for Abbott Laboratories, Pfizer, Hoffmann-LaRoche, GlaxoSmithKline, Bristol-Myers Squibb, Merck, Vertex, ViroLogic, and Tibotec/Virco. Dr Thompson has been a consultant for Abbott Laboratories, Agouron/Pfizer Pharmaceuticals, GlaxoSmithKline, Gilead Sciences, Serono, and Triangle Pharmaceuticals. Dr Volberding has been a consultant for Pfizer, Bristol-Myers Squibb, and Shire.

Dr Katzenstein holds a US patent for polymerase chain reaction assays monitoring antiviral therapy and making therapeutic decisions in the treatment of AIDS. Dr Montaner holds 2 US patents, one regarding use of nevirapine and another regarding pharmacological applications of mitochondrial DNA assays. Dr Montaner has 2 patent applications that are pending, one regarding pharmacological applications of mitochondrial DNA assays and another regarding sepsis.

Author Contributions:Study concept and design: Yeni, Hammer, Hirsch, Saag, Schechter, Carpenter, Fischl, Gatell, Jacobsen, Katzenstein, Montaner, Richman, Schooley, Vella, Volberding.

Acquisition of data: Yeni, Hirsch, Jacobsen, Katzenstein, Montaner, Vella, Volberding.

Analysis and interpretation of data: Yeni, Hammer, Hirsch, Saag, Carpenter, Gatell, Gazzard, Montaner, Richman, Thompson, Volberding.

Drafting of the manuscript: Yeni, Hammer, Hirsch, Saag, Schechter, Fischl, Gazzard, Jacobsen, Schooley, Volberding.

Critical revision of the manuscript for important intellectual content: Yeni, Hammer, Hirsch, Saag, Schechter, Carpenter, Gatell, Katzenstein, Montaner, Richman, Schooley, Thompson, Vella, Volberding.

Obtained funding: Hirsch, Jacobsen, Katzenstein, Montaner, Richman, Schooley, Vella, Volberding.

Administrative, technical, or material support: Hammer, Hirsch, Schechter, Jacobsen, Katzenstein, Montaner, Richman, Schooley, Vella.

Supervision: Yeni, Hammer, Hirsch, Carpenter, Gatell, Jacobsen, Katzenstein, Montaner, Richman, Schooley, Vella, Volberding.

Funding/Support: This work was sponsored and funded by the International AIDS Society-USA. No private sector or government funding contributed to this effort.

Acknowledgment: We thank Mai Vu, PharmD, for careful review of the information on interactions between drugs and Michelle Tayag for administrative support in preparing the manuscript.

JAMA: The Journal of the American Medical Association 292(2):p 251-265, July 14, 2004.

Context

Substantial changes in the field of human immunodeficiency virus (HIV) treatment have occurred in the last 2 years, prompting revision of the guidelines for antiretroviral management of adults with established HIV infection.

Objective

To update recommendations for physicians who provide HIV care regarding when to start antiretroviral therapy, what drugs to start with, when to change drug regimens, and what drug regimens to switch to after therapy fails.

Data Sources

Evidence was identified and reviewed by a 16-member noncompensated panel of physicians with expertise in HIV-related basic science and clinical research, antiretroviral therapy, and HIV patient care. The panel was designed to have broad US and international representation for areas with adequate access to antiretroviral management.

Study Selection

Evidence considered included published basic science, clinical research, and epidemiological data (identified by experts in the field or extracted through MEDLINE searches using terms relevant to antiretroviral therapy) and abstracts from HIV-oriented scientific conferences between July 2002 and May 2004.

Data Extraction

Data were reviewed to identify any information that might change previous guidelines. Based on panel discussion, guidelines were drafted by a writing committee and discussed by the panel until consensus was reached.

Data Synthesis

Four antiretroviral drugs recently have been made available and have broadened the options for initial and subsequent regimens. New data allow more definitive recommendations for specific drugs or regimens to include or avoid, particularly with regard to initial therapy. Recommendations are rated according to 7 evidence categories, ranging from I (data from prospective randomized clinical trials) to VII (expert opinion of the panel).

Conclusion

Further insights into the roles of drug toxic effects, drug resistance, and pharmacological interactions have resulted in additional guidance for strategic approaches to antiretroviral management.