Redistribution of human immunodeficiency virus type 1 variants resistant to protease inhibitors after a protease inhibitor-sparing regimen.
The redistribution of mutations related to protease inhibitor (PI) resistance after a PI-sparing regimen in human immunodeficiency virus (HIV)-infected, highly PI-experienced patients was prospectively assessed. Twenty-five patients failing a PI-including regimen were given PI-sparing antiretroviral therapy, and then followed for 24 weeks after PI resumption. Genotyping was performed by direct sequencing before and during the PI-sparing regimen. The median (interquartile range, IQR) baseline CD4+ T-lymphocyte count was 198 (120-255) cells/microl, and the median HIV-RNA level was 82,000 (41,000-300,000) copies/ml. Patients had experienced a median of 4.5 (4-5.25) PIs. The median number of PI mutations was eight (6-9). The PI-sparing regimen consisted of a median of three (3-4) drugs and lasted for a median of 53 (24-67) weeks. At the end of the study, the median number of PI mutations was 6.5 (6-9). The median change in the number of PI mutations was -1 (IQR from -1 to 0). A reduction from baseline was observed in 13 cases (52%); nine (36%) showed no change and three (12%) showed an increased number of PI substitutions. In highly PI-experienced patients, a PI-sparing regimen may lead to a reduction, no change, or increase in the number of PI mutations. The reduction is negligible in most cases.
Clinic of Infectious Diseases, Vita-Salute San Raffaele University, Milan, Italy. nicola.gianotti@hsr.it
Nicola
N
Gianotti
Elena
E
Seminari
Adriano
A
Lazzarin
Enzo
E
Boeri
Massimo
M
Clementi
Anna
A
Danise
Stefania
S
Salpietro
Giuliana
G
Fusetti
Antonella
A
Castagna
D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000627:therapeutic use; D018791:CD4 Lymphocyte Count; D004334:Drug Administration Schedule; D024882:Drug Resistance, Viral / Q000235:genetics*; D004359:Drug Therapy, Combination; D014644:Genetic Variation; D005838:Genotype; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology; D016333:HIV Protease / Q000235:genetics*; D017320:HIV Protease Inhibitors / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D015497:HIV-1 / Q000145:classification / Q000187:drug effects* / Q000201:enzymology / Q000235:genetics; D006801:Humans; D009154:Mutation; D012367:RNA, Viral / Q000097:blood; D018894:Reverse Transcriptase Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use
D019380:Anti-HIV Agents; D017320:HIV Protease Inhibitors; D012367:RNA, Viral; D018894:Reverse Transcriptase Inhibitors; D016333:HIV Protease