Replicative phenotyping adds value to genotypic resistance testing in heavily pre-treated HIV-infected individuals--the Swiss HIV Cohort Study

• Published in: Journal of translational medicine Vol. 9; no. 1; p. 14
• Main Authors: Fehr, Jan, Glass, Tracy R, Louvel, Séverine, Hamy, François, Hirsch, Hans H, von Wyl, Viktor, Böni, Jürg, Yerly, Sabine, Bürgisser, Philippe, Cavassini, Matthias, Fux, Christoph A, Hirschel, Bernard, Vernazza, Pietro, Martinetti, Gladys, Bernasconi, Enos, Günthard, Huldrych F, Battegay, Manuel, Bucher, Heiner C, Klimkait, Thomas
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 21.01.2011; BioMed Central; BMC
• Subjects: Adult; Anti-HIV Agents - pharmacology; Anti-HIV Agents - therapeutic use; Antiretroviral drugs; antiretroviral therapy; Antiviral agents; Cohort Studies; Diagnosis; Disease resistance; Dose-Response Relationship, Drug; Drug resistance; Drug Resistance, Viral - physiology; Drug therapy; Female; Genetic aspects; Genetic screening; Genotype; HIV; HIV infection; HIV Infections - diagnosis; HIV Infections - drug therapy; HIV Infections - virology; HIV-1 - physiology; Human immunodeficiency virus; Human immunodeficiency virus 1; Humans; Male; Microbial Sensitivity Tests - methods; Middle Aged; Multivariate analysis; Phenotype; Phenotyping; Predictive Value of Tests; Prognosis; Regression analysis; Replication; RNA; Shc protein; Studies; Switzerland; Translation; Viral drug resistance; Virus Replication - drug effects; Virus Replication - physiology; Switzerland
• ISSN: 1479-5876; 1479-5876
• DOI: 10.1186/1479-5876-9-14

Replicative phenotypic HIV resistance testing (rPRT) uses recombinant infectious virus to measure viral replication in the presence of antiretroviral drugs. Due to its high sensitivity of detection of viral minorities and its dissecting power for complex viral resistance patterns and mixed virus populations rPRT might help to improve HIV resistance diagnostics, particularly for patients with multiple drug failures. The aim was to investigate whether the addition of rPRT to genotypic resistance testing (GRT) compared to GRT alone is beneficial for obtaining a virological response in heavily pre-treated HIV-infected patients. Patients with resistance tests between 2002 and 2006 were followed within the Swiss HIV Cohort Study (SHCS). We assessed patients' virological success after their antiretroviral therapy was switched following resistance testing. Multilevel logistic regression models with SHCS centre as a random effect were used to investigate the association between the type of resistance test and virological response (HIV-1 RNA <50 copies/mL or ≥1.5 log reduction). Of 1158 individuals with resistance tests 221 with GRT+rPRT and 937 with GRT were eligible for analysis. Overall virological response rates were 85.1% for GRT+rPRT and 81.4% for GRT. In the subgroup of patients with >2 previous failures, the odds ratio (OR) for virological response of GRT+rPRT compared to GRT was 1.45 (95% CI 1.00-2.09). Multivariate analyses indicate a significant improvement with GRT+rPRT compared to GRT alone (OR 1.68, 95% CI 1.31-2.15). In heavily pre-treated patients rPRT-based resistance information adds benefit, contributing to a higher rate of treatment success.