Ms. Hirsch et al., ANTIRETROVIRAL DRUG-RESISTANCE TESTING IN ADULTS WITH HIV-INFECTION -IMPLICATIONS FOR CLINICAL MANAGEMENT, JAMA, the journal of the American Medical Association, 279(24), 1998, pp. 1984-1991
Objectives.-To review current knowledge of the biology and clinical im
plications of human immunodeficiency virus (HIV) resistance to antiret
roviral drugs, describe assays for measuring resistance, and assess th
eir use in clinical practice. Participants.-The international AIDS Soc
iety-USA assembled a panel of 13 physicians with expertise in basic sc
ience, clinical research, and patient care relevant to HIV resistance
to antiretroviral drugs. Evidence.-We reviewed available data from pub
lished reports and presented at national and international research co
nferences. Basic science research, clinical trial results, and expert
opinions were used to form the basis of this report, Data on methods f
or and characteristics of specific genotypic and phenotypic assays wer
e obtained from manufacturers and service providers. Consensus Process
.-The panel met regularly between October 1997 and April 1998, Panel s
ubgroups developed and discussed different sections of the report befo
re discussing them with the entire panel. Conclusions and suggested ap
proaches to the use of resistance testing were determined by group con
sensus. Conclusions.-Plasma HIV RNA level and CD4(+) cell count are th
e primary values that should be used to guide the initiation of antire
troviral therapy and subsequent changes in therapy. Possible causes of
treatment failure other than development of drug resistance that shou
ld be considered are adherence, drug potency, and pharmacokinetic issu
es, Genotypic and phenotypic testing for HIV resistance to antiretrovi
ral drugs may prove useful for individual patient management. Assays u
nder development need validation, standardization, and a clearer defin
ition of their clinical roles, Possible current roles of resistance te
sting for choosing an initial regimen or changing antiretroviral thera
py, as well as possible implications of the presence or absence of phe
notypic resistance and genotypic changes, are discussed.