February 10, 2004
The study enrolled 137 patients, 78 in the genotype arm (using the Viroseq HIV-1 genotyping assay) and 58 in the phenotype arm (using the Antivirogram). The average patient age was about 40, and the average CD4 count and viral load was about 230 cells/mm3 and 4.6 log/ml, respectively. The two groups were fairly evenly matched with respect to the number of previous HAART regimens, and specific HIV drugs or classes that each had previously received. Expert advice was defined as an independent committee composed of a virologist, a clinician expert in interpreting resistance tests and the treating physician who decided on the most appropriate regimen for the patient.
The data was analyzed by intent-to-treat (ITT) analysis -- in which dropouts were considered failures -- and by the less rigorous on-treatment (OT) analysis, in which these dropouts were not included in the final analysis. Viral load and CD4 count were measured at 12, 24, 36 and 48 weeks. At week 48, the average drop in viral load was just over a 1.5-log/ml reduction for both the genotype and phenotype arms. This was not significantly different. In terms of the number of patients who achieved an undetectable viral load (<200 copies/mL), the phenotype group was slightly better (38% versus 28%, P = NS) than the genotype group in the ITT analysis, and about equal in the OT analysis (44% versus 41%, P = NS). There was a slight advantage for genotyping with respect to CD4 cell increase (88 versus 69 cells/mm3, P = NS).
This study demonstrates -- in a very treatment-experienced group of patients -- that there does not appear to be any advantage to using one type of resistance test over another when expert advice is available for interpretation of the test result and a suggested new regimen. It is often thought the genotypic resistance tests may be somewhat harder to interpret, given the numerous genetic sequence changes conferring HIV drug resistance that must be remembered and applied to the interpretation of genotypic tests. Even when algorithms are provided and used in the interpretation of these tests, differences exist as to the significance of some sequence changes among these algorithms and the experts who develop them. Phenotypic tests are thought to be more easily interpretable by practicing clinicians, since the reports indicate whether a patient's viral strain is susceptible or not to a particular drug based on growth characteristics in the presence of HIV drugs.
Several studies have determined that either genotypic or phenotypic resistance testing is superior to standard of care (SOC) alone without the benefit of resistance test results. Studies are split on the superiority of one technology over the other in conferring a better virologic outcome. One previous study (the Havana trial) indicated that expert opinion associated with genotypic resistance testing resulted in better virologic outcome, when compared to genotypic results alone used by the treating physician. Phenotyping was not assessed in that study.
The current study further indicates no superiority of either technology even when expert opinion is provided for interpretation. There is a cost differential between these two types of resistance tests. Phenotypic resistance testing is more expensive and can require more time to produce results when compared to genotypic testing. Whether there is any advantage of one testing method over the other, or the use of expert advice in less advanced or less heavily treatment-experienced patients requires further study.
Abstract: Genotypic vs. Real Phenotypic Tests to Guide Salvage Antiretroviral Therapy in Heavily Pretreated Patients With Virological Failure: A 48 Weeks Prospective, Randomized Study (VIHRES Study) (Poster 675)
Authored by: J. Blanco, A. Guelar, P. Domingo, E. De Lazari, G. Valdecillo, J. R. Arroyo, A. Biglia, M. Arnedo, H. Knobel, T. Pumarola, J. M. Gatell, J. Mallolas
Affiliations: Hosp. Clin., Barcelona, Spain; Hosp. del Mar, Barcelona, Spain; Hosp. Santa Creu i San Pau, Barcelona, Spain
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