title: Real versus virtual phenotype to guide treatment in heavily pretreated patients: 48-week follow-up of the Genotipo-Fenotipo di Resistenza (GenPheRex) trial.
abstract: We compared viroimmunologic response after real phenotype (r-PHT) versus virtual phenotype (v-PHT) in patients failing highly active antiretroviral therapy (HAART). A total of 201 patients with >2 years of exposure, more than six experienced drugs, >1000 HIV RNA copies/mL, and on stable HAART for >6 months were randomized to the r-PHT or v-PHT arm. The primary end point was the proportion of HIV plasma viral load (pVL) <400 copies/mL. Secondary end points were absolute pVL change, proportion of pVL reduction >0.5 log(10) copies/mL, and absolute CD4 cell change. In the intention-to-treat-last observation carried forward analysis, study outcomes were not significantly different between arms over 48 weeks of follow-up: 20% and 24% pVL <400 copies/mL; 58% and 61% pVL reduction >0.5 log(10) copies/mL; -0.92 and -0.94(10) log copies/mL mean pVL decrease; and +41.6 and +94.4 cells/mm(3) mean absolute CD4 increase in the r-PHT and v-PHT arms, respectively. On-treatment analyses gave similar results. In the multivariate analysis of pVL <400 copies/mL, the following covariates were independent predictors at week 48: adherence (OR p= 0.25; p=.002), baseline CD4 (OR = 4.39; p=.007), intravenous drug use as risk factor for HIV acquisition (OR = 0.33; p=.024), and sensitivity score of the new regimens by biologic cut-offs (OR = 1.84; p=.029). Prescribed drugs for which patients were naive resulted in marginal prediction (OR = 1.93; p=.054). In conclusion, virologic and immunologic outcomes did not differ when r-PHT or v-PHT was used in this cohort of heavily pretreated patients. Several factors should be considered to take better advantage of resistance testing, including treatment history, clinical status, and patients' ability to adhere to treatment.
authors.affiliation: Department of Infectious Diseases, S.M. Annunziata Hospital, ASL Firenze, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Mazzotta
authors.forename: Sergio
authors.initials: S
authors.lastname: Lo Caputo
authors.forename: Carlo
authors.initials: C
authors.lastname: Torti
authors.forename: Carmine
authors.initials: C
authors.lastname: Tinelli
authors.forename: Piera
authors.initials: P
authors.lastname: Pierotti
authors.forename: Francesco
authors.initials: F
authors.lastname: Castelli
authors.forename: Adriano
authors.initials: A
authors.lastname: Lazzarin
authors.forename: Gioacchino
authors.initials: G
authors.lastname: Angarano
authors.forename: Renato
authors.initials: R
authors.lastname: Maserati
authors.forename: Nicola
authors.initials: N
authors.lastname: Gianotti
authors.forename: Nicoletta
authors.initials: N
authors.lastname: Ladisa
authors.forename: Eugenia
authors.initials: E
authors.lastname: Quiros-Roldan
authors.forename: Alex R
authors.initials: AR
authors.lastname: Rinehart
authors.forename: Giampiero
authors.initials: G
authors.lastname: Carosi
mesh_terms: D000328:Adult; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D023241:Antiretroviral Therapy, Highly Active; D018791:CD4 Lymphocyte Count; D015331:Cohort Studies; D024882:Drug Resistance, Viral / Q000235:genetics*; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology / Q000821:virology; D015497:HIV-1 / Q000187:drug effects* / Q000235:genetics*; D006801:Humans; D007558:Italy; D008297:Male; D015999:Multivariate Analysis; D010641:Phenotype; D016896:Treatment Outcome; D019562:Viral Load
chemical_list: D019380:Anti-HIV Agents