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

• Published in: Clinical infectious diseases Vol. 42; no. 10; pp. 1470 - 1480
• Main Authors: Gianotti, Nicola, Mondino, Vincenzo, Rossi, Maria Cristina, Chiesa, Elisabetta, Mezzaroma, Ivano, Ladisa, Nicoletta, Guaraldi, Giovanni, Torti, Carlo, Tarquini, Pierluigi, Castelli, Paula, Di Carlo, Aldo, Boeri, Enzo, Keulen, Wilco, Mc Kenna, Paula, Lazzarin, Adriano
• Format: Journal Article
• Language: English
• Published: Chicago, IL The University of Chicago Press 15.05.2006; University of Chicago Press; Oxford University Press
• Subjects: Adult; AIDS; Algorithms; Amino acids; Anti-HIV Agents - therapeutic use; Antiretroviral agents; Antiretroviral drugs; Antiretroviral Therapy, Highly Active; Antiretrovirals; Antivirals; Biological and medical sciences; Clinical trials; Female; Genetic algorithms; Genetic mutation; Genotype; Genotype & phenotype; Genotypes; HIV; HIV - genetics; HIV Infections - drug therapy; HIV Protease Inhibitors - therapeutic use; HIV/AIDS; Human immunodeficiency virus; Human viral diseases; Humans; Immunodeficiencies; Immunodeficiencies. Immunoglobulinopathies; Immunopathology; Infectious diseases; Italy; Lymphocytes; Male; Medical sciences; Middle Aged; Mutation; Phenotype; Phenotypes; Proteinase inhibitors; Reverse Transcriptase Inhibitors - therapeutic use; RNA; RNA, Viral - blood; RNA, Viral - genetics; Salvage Therapy; Statistical significance; Viral diseases; Viral diseases of the lymphoid tissue and the blood. Aids; Viral Load; Virology; Italy; Immunopathology; Typing; Genotype; AIDS; Immune deficiency; Algorithm; Infection; Phenotype; Microbiological investigation; Viral disease; Clinical trial; Mutation; Salvage treatment; Comparative study
• ISSN: 1058-4838; 1537-6591; 1537-6591
• DOI: 10.1086/503568

Background. There is still considerable uncertainty as to the best algorithm for interpreting human immunodeficiency 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, 4.1 ± 0.74 log10 copies/mL; CD4+ T lymphocyte count, 410 ± 262 cells/µL; reverse-transcriptase mutations, 4.8 ± 2.9; and protease 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.