From Harvard Medical School, Boston, Mass (Drs Hirsch, Hammer, and D'Aquila); St. Paul's Hospital, Vancouver, British Columbia (Dr Conway); University of Alabama at Birmingham School of Medicine and Birmingham Veterans Affairs Medical Center, Birmingham (Dr Johnson); Hôpital Bichat-Claude Bernard, Paris, France (Dr Brun-Vézinet); Fundacio irsaCaixa and HIV Unit, Hospital Universitari Germans Trias i Pujol, Barcelona, Spain (Dr Clotet); University of Rochester, Rochester, NY (Dr Demeter); The International AIDS Society–USA, San Francisco, Calif (Ms Jacobsen); University of Colorado Health Sciences Center, Denver (Dr Kuritzkes); The Royal Free Hospital Medical School, London, England (Dr Loveday); University of Pittsburgh Medical Center, Pittsburgh, Pa (Dr Mellors); Istituto Superiore di Sanità, Rome, Italy (Dr Vella); and University of California San Diego and San Diego Veterans Affairs Medical Center, San Diego (Dr Richman).
Objectives.— To review current knowledge of the biology and clinical implications
of human immunodeficiency virus (HIV) resistance to antiretroviral drugs,
describe assays for measuring resistance, and assess their use in clinical
Participants.— The International AIDS Society-USA assembled a panel of 13 physicians
with expertise in basic science, clinical research, and patient care relevant
to HIV resistance to antiretroviral drugs.
Evidence.— We reviewed available data from published reports and presented at national
and international research conferences. Basic science research, clinical trial
results, and expert opinions were used to form the basis of this report. Data
on methods for and characteristics of specific genotypic and phenotypic assays
were obtained from manufacturers and service providers.
Consensus Process.— The panel met regularly between October 1997 and April 1998. Panel subgroups
developed and discussed different sections of the report before discussing
them with the entire panel. Conclusions and suggested approaches to the use
of resistance testing were determined by group consensus.
Conclusions.— Plasma HIV RNA level and CD4+ cell count are the primary
values that should be used to guide the initiation of antiretroviral therapy
and subsequent changes in therapy. Possible causes of treatment failure other
than development of drug resistance that should be considered are adherence,
drug potency, and pharmacokinetic issues. Genotypic and phenotypic testing
for HIV resistance to antiretroviral drugs may prove useful for individual
patient management. Assays under development need validation, standardization,
and a clearer definition of their clinical roles. Possible current roles of
resistance testing for choosing an initial regimen or changing antiretroviral
therapy, as well as possible implications of the presence or absence of phenotypic
resistance and genotypic changes, are discussed.
Hirsch MS, Conway B, D'Aquila RT, Johnson VA, Brun-Vézinet F, Clotet B, Demeter LM, Hammer SM, Jacobsen DM, Kuritzkes DR, Loveday C, Mellors JW, Vella S, Richman DD, for the International AIDS Society–USA Panel . Antiretroviral Drug Resistance Testing in Adults With HIV InfectionImplications for Clinical Management. JAMA. 1998;279(24):1984-1991. doi:10.1001/jama.279.24.1984