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.

[1]  A. Lazzarin,et al.  Boosted protease inhibitor-including versus a protease inhibitor-sparing regimen in protease inhibitor-resistant HIV-infected patients: 24-week immunological outcome , 2004, AIDS (London).

[2]  A. Lazzarin,et al.  Predictors of sustained response to therapy resumption after treatment interruption in HIV‐infected patients failing antiretroviral therapy , 2004, Journal of medical virology.

[3]  A. Lazzarin,et al.  Evolutionary characteristics of HIV type 1 variants resistant to protease inhibitors in the absence of drug-selective pressure. , 2003, AIDS research and human retroviruses.

[4]  Gary Collins,et al.  Structured treatment interruption in patients with multidrug-resistant human immunodeficiency virus. , 2003, The New England journal of medicine.

[5]  P. Lichtenberger,et al.  Effect of class-specific therapy interruption on persistence of HIV type 1 antiretroviral resistance. , 2003, AIDS research and human retroviruses.

[6]  R. Shafer,et al.  Drug resistance mutations in HIV-1. , 2003, Topics in HIV medicine : a publication of the International AIDS Society, USA.

[7]  P. Massip,et al.  Virological and immunological effects of salvage therapy following treatment interruption and a shift in HIV‐1 resistance genotype , 2002, Journal of medical virology.

[8]  Robert W. Shafer,et al.  Genotypic Testing for Human Immunodeficiency Virus Type 1 Drug Resistance , 2002, Clinical Microbiology Reviews.

[9]  R Hoh,et al.  Virologic and immunologic consequences of discontinuing combination antiretroviral-drug therapy in HIV-infected patients with detectable viremia. , 2001, The New England journal of medicine.

[10]  K. Hertogs,et al.  Virological and immunological effects of treatment interruptions in HIV-1 infected patients with treatment failure , 2000, AIDS.

[11]  P. Massip,et al.  Shift in HIV resistance genotype after treatment interruption and short-term antiviral effect following a new salvage regimen , 2000, AIDS.

[12]  R. Sherer,et al.  Management of the adverse effects of antiretroviral therapy and medication adherence. , 2000, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.