BACKGROUND: Drug resistance of HIV-1 is an obstacle to the long-term efficacy of antiretroviral therapy. OBJECTIVE: To characterize reverse transcriptase and protease genes of multidrug-resistant HIV-1 isolates. DESIGN: Descriptive case series. SETTING: Academic medical center. PATIENTS: Four consecutive patients with HIV-1 infection were selected because they had previously received many antiretroviral drugs and had not achieved plasma HIV-1 RNA suppression despite treatment with several three-drug combinations. MEASUREMENTS: Reverse transcriptase sequencing, protease sequencing, and drug susceptibility testing of HIV-1. RESULTS: Isolates of HIV-1 from the four patients shared seven protease mutations and eight reverse transcriptase mutations. These mutations were present in biological clones and at three time points in three of the patients. Susceptibility testing showed high-level resistance (30-fold to >100-fold) to zidovudine, lamivudine, saquinavir, indinavir, and nelfinavir and lower-level resistance (3-fold to 5-fold) to didanosine, zalcitabine, and stavudine. CONCLUSIONS: Simultaneous resistance to almost all available antiretroviral drugs may occur in HIV-1. The concordance and persistence of mutations in drug-resistant HIV-1 isolates suggest that some combinations of reverse transcriptase and protease mutations give the virus a selective advantage in the presence of various drug combinations.
BACKGROUND: Drug resistance of HIV-1 is an obstacle to the long-term efficacy of antiretroviral therapy. OBJECTIVE: To characterize reverse transcriptase and protease genes of multidrug-resistant HIV-1 isolates. DESIGN: Descriptive case series. SETTING: Academic medical center. PATIENTS: Four consecutive patients with HIV-1 infection were selected because they had previously received many antiretroviral drugs and had not achieved plasma HIV-1 RNA suppression despite treatment with several three-drug combinations. MEASUREMENTS: Reverse transcriptase sequencing, protease sequencing, and drug susceptibility testing of HIV-1. RESULTS: Isolates of HIV-1 from the four patients shared seven protease mutations and eight reverse transcriptase mutations. These mutations were present in biological clones and at three time points in three of the patients. Susceptibility testing showed high-level resistance (30-fold to >100-fold) to zidovudine, lamivudine, saquinavir, indinavir, and nelfinavir and lower-level resistance (3-fold to 5-fold) to didanosine, zalcitabine, and stavudine. CONCLUSIONS: Simultaneous resistance to almost all available antiretroviral drugs may occur in HIV-1. The concordance and persistence of mutations in drug-resistant HIV-1 isolates suggest that some combinations of reverse transcriptase and protease mutations give the virus a selective advantage in the presence of various drug combinations.
Authors: A Plettenberg; D Albrecht; T Lorenzen; V Paech; H Petersen; T Fenner; T Meyer; R Arndt; K Hertogs; R Pauwels; T Weitzel; A Stoehr Journal: Sex Transm Infect Date: 2001-12 Impact factor: 3.519
Authors: Matthew J Gonzales; Ilana Belitskaya; Kathryn M Dupnik; Soo-Yon Rhee; Robert W Shafer Journal: AIDS Res Hum Retroviruses Date: 2003-10 Impact factor: 2.205
Authors: D C Sayer; S Land; L Gizzarelli; M French; G Hales; S Emery; F T Christiansen; E M Dax Journal: J Clin Microbiol Date: 2003-01 Impact factor: 5.948
Authors: Galina N Nikolenko; Sarah Palmer; Frank Maldarelli; John W Mellors; John M Coffin; Vinay K Pathak Journal: Proc Natl Acad Sci U S A Date: 2005-01-31 Impact factor: 11.205