Antiretroviral Drug Resistance Testing in Adult HIV-1 Infection: Recommendations of an International AIDS Society-USA Panel [MS Hirsch, et al. JAMA 2000;283:2417]: This paper presents the recommendations of IAS-USA for the use of HIV resistance testing. The panel consisted of 13 physicians with expertise relevant to this issue, the conclusions were based on data collected through April 2000, and the authors state that this is intended to update the January publication of recommendations for antiretroviral therapy of adults by IAS-USA. With regard to testing methods, the panel states the relative advantages and disadvantages of phenotypic and genotypic susceptibility testing, but do not clearly state a preference for either. The panel has provided an excellent updated resistance map summarizing the major and minor codon mutations conferring drug-specific resistance:

Resistance Mutations
Drug	Major	Minor
Nucleosides
AZT	70, 151, 215	41, 67, 210, 219
3TC	44, 118, 151, 184	-
ddC	65, 69, 74, 151, 184	-
d4T	69, 151	50, 75, 178
ABC	65, 69, 74, 151, 184	41, 76, 70, 115, 210, 215, 219
MultiNRTI	69, 151	41, 62, 67, 70, 75, 77, 115, 116, 210, 215, 219
NNRTI
NVI	103, 106, 108, 181, 188, 190	100
DLV	103, 181	236
EFV	103, 188, 190	100, 108, 225
Protease inhibitors
IDV	46, 82	10, 20, 24, 32, 36, 54, 71, 73, 77, 84, 90, 99
NFV	30, 90	10, 36, 46, 71, 73, 77, 82, 84, 88
RTV	82	20, 32, 33, 36, 46, 54, 71, 84, 90
SQV	48, 90	10, 20, 24, 30, 36, 46, 54, 63, 71, 73, 77, 82, 84
APV	50, 84	10, 32, 46, 47, 54

The real beef of the article concerns the recommendations for resistance testing by specific clinical settings. These are divided into two categories defined as follows: "recommended" means a 100% consensus that there is sufficient evidence to recommend routine use in the designated setting. "Consider" indicates there is support from preliminary data, but the evidence is not yet convincing enough to warrant routine use. Based on these definitions, the following recommendations are made:

Recommendations for HIV Resistance Testing [IAS-USA, April 2000, JAMA 2000;283:2424]
Setting	Recommendation	Comment
Primary HIV	Consider	Goal is to detect transmission of resistant strains to optimize therapy.
Established HIV infection untreated	Consider	It may not be possible to detect resistant strains. Strength of recommendation is increased in locations with increased primary HIV drug resistance.
Established HIV infection - retreatment	Recommended	Must first rule out non-adherence and pharmacokinetic reasons for drug failure. Test with virologic failure at 4 - 12 weeks to detect emergence of resistant strains that were transmitted. Test with later virologic failure to detect resistance that developed after transmission.
Established HIV infection - multiple failures	Recommended	Goal is to optimize drug selection by excluding drugs that are unlikely to be effective.
Pregnancy	Recommended	Goal is optimal treatment of the mother and optimal protection of the neonate.

Comment: This is an excellent document from a highly qualified panel of experts, clearly the leaders in this field. These results are distinctly different from those of the IAS panel that did not recommend resistance testing because that panel considered that the supporting clinical data were unconvincing and that technical aspects of the assay needed to be further refined. The current IAS-USA panel notes that the recommendations summarized above represent an updated version, although it is expected that the marked differences in recommendation may represent idiosyncrasies of membership on the panels as well. The recommendations of the panel summarized above are more commensurate with the recommendations of the DHHS panel, which recommended resistance testing for primary HIV infection and for regimen selection after treatment failure; the issue of resistance testing in pregnancy was not addressed by the DHHS panel since this is relegated to another panel that deals with pregnancy issues. Scrutiny of the recommendations of IAS-USA show that resistance testing is either recommended or should be considered in virtually everyone with HIV infection who is a candidate for antiretroviral therapy. This obviously represents one of the major evolutionary changes in HIV management of the past year. posted 5/22/2000