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How Does Expert Advice Impact Genotypic Resistance Testing in Clinical Practice?
  Clinical Infectious Diseases September 1, 2003;37:708-713
Sheila M. Badri,1,2,3 Oluwatoyin M. Adeyemi,1,2,3 Blake E. Max,3,4 Brandon M. Zagorski,1 and David E. Barker1,2,3. 1Division of Infectious Diseases, John H. Stroger, Jr. Hospital of Cook County, 2Rush Medical College, 3CORE Center, Cook County Bureau of Health, and 4University of Illinois at Chicago College of Pharmacy, Chicago, Illinois
The Havana trial, a randomized, prospective study, demonstrated that expert interpretation of genotypic resistance test (GRT) results improved virological outcomes in human immunodeficiency virus type 1 (HIV-1)infected patients for whom highly active antiretroviral therapy (HAART) was failing.
The impact of expert advice in routine clinical practice is unknown. We retrospectively evaluated the virological outcomes of 74 patients for whom HAART was failing and whose clinical providers accepted or rejected HAART regimens recommended by an expert panel who routinely reviewed GRT results.
Fifty (68%) of 74 patients received regimens recommended by the expert panel ("advice accepted" [AA]), and 24 patients (32%) received regimens per the clinician's preference ("advice rejected" [AR]).
After 24 weeks, AA and AR groups had median decreases in the plasma HIV-1 RNA viral load of 2.6 and 1.3 log10 copies/mL, respectively (P = .0001).
Twenty-six (52%) of 50 patients in the AA group and 5 (21%) of 24 patients in the AR group had a plasma HIV-1 RNA viral load of <50 copies/mL (P = .01).
Consideration should be given to enlisting expert assistance in the interpretation of GRT results in routine clinical practice.
More Details
All patients who underwent GRTs were stratified into those experiencing their first, second, or third or more HAART regimen failure. The education level of each patient's medical provider was determined.
Baseline characteristics of patients in the AA and AR groups were similar. All patients had experience with antiretroviral therapy, with exposure to a mean (±SD) of 6.1 ± 2.3 antiretroviral agents. There was no difference in individual antiretroviral use between the AA and AR groups. Overall, 64% and 93% of patients had prior exposure to an NNRTI and PI, respectively. The proportion of patients for whom the first, second, or third or greater HAART regimen had failed was also similar between the 2 groups.
The virological response to antiretroviral therapy was significantly greater for patients in the AA group than for those in the AR group. When data were stratified on the basis of the number of previous HAART regimens, a significant stratum effect was observed. Only patients in the AA group for whom a second HAART regimen was failing had a significantly better virological response than did patients in the AR group (median decrease in plasma HIV-1 RNA viral load, 2.7 vs. 0.6 log10 copies/mL; P = .007). Patients in the AA group for whom 3 regimens had failed had a good virological response to HAART, compared with patients in the AR group; this finding approached statistical significance (median decrease in plasma HIV-1 RNA viral load, 2.5 vs. 0.3 log10 copies/mL; P = .06). The virological response in patients in the AR group also correlated with the number of active drugs recommended by the expert panel. The AR0, AR1, and AR2 subgroups had mean decreases in the viral load (±SD) of 0.13 ± 0.25, 0.64 ± 0.91, and 1.74 ± 1.1, respectively. A plasma HIV-1 RNA viral load of <50 copies/mL at 24 weeks was present in 52% of patients in the AA group and 21% of patients in the AR group (P = .01).
The results of this study should be interpreted in light of its limitations. This was a nonrandomized, retrospective study with a relatively small number of patients. In addition, the reasons for rejecting expert advice could only be determined by chart review for 9 patients in the AR group. Other factors, such as past drug toxicity, psychosocial issues, patient apprehension regarding drug toxicities or pill burden of HAART regimens, or provider attitude towards the utility of GRTs and expert advice, could not be determined. These variables constitute some of the unmeasured differences between the AA and AR groups that may have influenced the outcomes. Additional prospective, observational, clinic-based studies are needed to take into account these variables. Finally, the long-term durability of viral suppression in patients whose HAART regimens are based on GRT findings and expert advice remains to be demonstrated. Despite these limitations, we felt the need to present data reflecting the impact of expert advice on GRT results in a large, urban clinical practice in a setting outside of clinical trials.
We found that virological outcome is improved when HAART regimens are changed on the basis expert interpretation of GRT results, especially in patients for whom a second regimen is failing. Because cross-resistance between drugs is evident, and because the number of antiretroviral agents available for the treatment of HIV-1 infection is limited, changes in antiretroviral therapy may be better aided by expert interpretation of GRT results. Medical providers who care for HIV-infected patients should consider creating groups who are familiar with resistance mutations to review GRT data in clinical practice.
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