Comparison of a rule-based algorithm with a phenotype-based algorithm for the interpretation of HIV genotypes in guiding salvage regimens in HIV-infected patients by a randomized clinical trial: The mutations and salvage study

Background. There is still considerable uncertainty as to the best algorithm for interpreting humanimmunodeficiency virus (HIV) genotyping results. Methods. A total of 318 subjects with HIV RNA levels of > 1000 copies/mL were enrolled in 41 centers throughout Italy from 2001 through 2003, stratified on the basis of their drug history, randomized (1:1) to 2 arms to have their treatments modified on the basis of the results of HIV genotyping (as interpreted by virtual phenotype analysis or with use of a rule-based interpretation system), and followed up for 48 weeks. At least 1 nucleoside reverse-transcriptase inhibitor and 1 protease inhibitor had to be included in any new regimen; nonnucleoside reverse-transcriptase inhibitor naive patients were also prescribed a nonnucleoside reverse-transcriptase inhibitor. Only drugs licensed in Italy were allowed. The primary end point was a decrease in HIV RNA level to < 400 copies/mL by week 12 according to on-treatment analysis. Results. The mean (+/- standard deviation) values at baseline were as follows: HIV RNA level, log(10) copies/mL; CD4(+) T lymphocyte count, cells/mu L; reverse-transcriptase mutations,4.8 +/- 2.9; and protease mutationa, mutations, 2.8 +/- 2.5. There were 133 patients (41.8%) who were nonnucleoside reverse-transcriptase inhibitor naive and protease inhibitor experienced, 63 patients (19.8%) who were nonnucleoside reverse- transcriptase inhibitor experienced and protease inhibitor naive, and 122 patients (38.4%) who were 3-class experienced. A total of 192 patients completed 12 weeks of the treatment regimen assigned at baseline; at 12 weeks, 66.3% of patients in the virtual phenotype arm and 71.3% of patients in the rule-based interpretation arm had HIV RNA levels of ! 400 copies/ mL (P = .46). No statistically significant difference between arms was observed by intention-to-treat analysis. Conclusion. Both the virtual phenotype and rule-based interpretation methods of HIV genotyping can guide the selection of effective antiretroviral drugs for a salvage regimen.