scholarly journals Efficient Suppression of Minority Drug‐Resistant HIV Type 1 (HIV‐1) Variants Present at Primary HIV‐1 Infection by Ritonavir‐Boosted Protease Inhibitor–Containing Antiretroviral Therapy

2010 ◽  
Vol 201 (7) ◽  
pp. 1063-1071 ◽  
Author(s):  
Karin J. Metzner ◽  
Pia Rauch ◽  
Viktor von Wyl ◽  
Christine Leemann ◽  
Christina Grube ◽  
...  
Keyword(s):  
Antiretroviral Therapy ◽  
Protease Inhibitor ◽  
Drug Resistant ◽  
Efficient Suppression ◽  
Hiv Type 1 ◽  
Hiv 1

Antiretroviral Drug-Resistant Mutations at Baseline and at Time of Failure of Antiretroviral Therapy in HIV Type 1-Coinfected TB Patients

2009 ◽  
Vol 25 (11) ◽  
pp. 1179-1185 ◽  
Author(s):  
Lakshmi Rajesh ◽  
Ramesh Karunaianantham ◽  
Paranji R. Narayanan ◽  
Soumya Swaminathan
Keyword(s):  
Antiretroviral Therapy ◽  
Drug Resistant ◽  
Antiretroviral Drug ◽  
Hiv Type 1 ◽  
Time Of Failure

scholarly journals Emergence of protease inhibitor resistance mutations in human immunodeficiency virus type 1 isolates from patients and rapid screening procedure for their detection.

1996 ◽  
Vol 40 (11) ◽  
pp. 2535-2541 ◽  
Author(s):  
M B Vasudevachari ◽  
Y M Zhang ◽  
H Imamichi ◽  
T Imamichi ◽  
J Falloon ◽  
...  
Keyword(s):  
Amino Acid ◽  
Protease Inhibitor ◽  
Pcr Amplification ◽  
Rapid Screening ◽  
Protease Gene ◽  
Drug Resistant ◽  
Reverse Transcription Pcr ◽  
Immunodeficiency Virus ◽  
Hiv 1

Patient human immunodeficiency virus type 1 (HIV-1) isolates that are resistant to protease inhibitors may contain amino acid substitutions L10I/V, M46L/I, G-48V, L63P, V82A/F/T, I84V, and L90M in the protease gene. Substitutions at positions 82 and/or 90 occur in variants that display high levels of resistance to certain protease inhibitors. Nucleotide substitutions at these two sites also lead to the loss of two HindII restriction enzyme digestion sites, and these changes make possible a rapid procedure for the detection of drug-resistant variants in patients on protease inhibitor therapy. This procedure was used to detect the emergence of mutated viruses at various times after the initiation of therapy with the HIV-1 protease inhibitor indinavir. The method includes viral RNA isolation from plasma and reverse transcription PCR amplification of the protease gene with fluorescence-tagged primers. The PCR product is digested with HindII, the cleavage products are separated on a urea-acrylamide gel in a DNA sequencer, and the extent of cleavage is automatically analyzed with commercially available software. In viruses from 34 blood samples from four patients, mutations leading to an amino acid change at residue 82 appeared as early as 6 weeks after the start of therapy and persisted throughout the course of the study period (48 weeks). Mutations leading to double substitutions at residues 82 and 90 were seen at a lower frequency and appeared later than the change at position 82. The changes detected by restriction enzyme cleavage were confirmed by DNA sequencing of the cloned protease genes by reverse transcription PCR amplification of viral RNA from isolates in plasma. In addition to the changes at positions 82 and 90, we have identified M46L/I, G48V, and I54V substitutions in isolates derived from indinavir-treated patients. HindII analysis of uncloned, PCR-amplified DNA offers a rapid screening procedure for the detection of virus isolates containing mutations at amino acid residues 82 and 90 in the HIV-1 protease gene. By using other restriction enzymes, the same method can be used to detect additional protease drug-resistant variants and is generally applicable for the detection of mutations.

Prevalence of Drug-Resistant HIV Type 1 at the Time of Initiation of Antiretroviral Therapy in Portland, Oregon

2013 ◽  
Vol 29 (2) ◽  
pp. 337-342 ◽  
Author(s):  
Michael S. MacVeigh ◽  
Maria K. Kosmetatos ◽  
James E. McDonald ◽  
Joan L. Reeder ◽  
Debby A. Parrish ◽  
...  
Keyword(s):  
Antiretroviral Therapy ◽  
Drug Resistant ◽  
Hiv Type 1

scholarly journals Efficient Identification of Human Immunodeficiency Virus Type 1 Mutants Resistant to a Protease Inhibitor by Using a Random Mutant Library

2011 ◽  
Vol 55 (11) ◽  
pp. 5090-5098 ◽  
Author(s):  
Sanggu Kim ◽  
Yun-Cheol Kim ◽  
Hangfei Qi ◽  
Kunkai Su ◽  
Sherie L. Morrison ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Drug Resistance ◽  
Protease Inhibitor ◽  
Human Immunodeficiency Virus Type ◽  
Virus Type ◽  
Drug Resistant ◽  
Immunodeficiency Virus ◽  
Hiv 1

ABSTRACTEmergence of drug-resistant mutant viruses during the course of antiretroviral therapy is a major hurdle that limits the success of chemotherapeutic treatment to suppress human immunodeficiency virus type 1 (HIV-1) replication and AIDS progression. Development of new drugs and careful patient management based on resistance genotyping data are important for enhancing therapeutic efficacy. However, identifying changes leading to drug resistance can take years of clinical studies, and conventionalin vitroassays are limited in generating reliable drug resistance data. Here we present an efficientin vitroscreening assay for selecting drug-resistant variants from a library of randomly mutated HIV-1 strains generated by transposon-directed base-exchange mutagenesis. As a test of principle, we screened a library of mutant HIV-1 strains containing random mutations in the protease gene by using a reporter T-cell line in the presence of the protease inhibitor (PI) nelfinavir (NFV). Analysis of replicating viruses from a single round of infection identified 50 amino acid substitutions at 35 HIV-1 protease residue positions. The selected mutant viruses showed specific resistance to NFV and included most of the known NFV resistance mutations. Therefore, the new assay is efficient for identifying changes leading to drug resistance. The data also provide insights into the molecular mechanisms underlying the development of drug resistance.

scholarly journals Prevalence of HIV Drug Resistance Mutations in HIV Type 1 Isolates in Antiretroviral Therapy Naïve Population from Northern India

2012 ◽  
Vol 2012 ◽  
pp. 1-6 ◽  
Author(s):  
S. Sinha ◽  
H. Ahmad ◽  
R. C. Shekhar ◽  
N. Kumar ◽  
L. Dar ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Antiretroviral Therapy ◽  
Resistance Mutations ◽  
Subtype C ◽  
Hiv Drug Resistance ◽  
Northern India ◽  
Subtype B ◽  
Hiv Type 1 ◽  
Hiv 1

Objective. The increased use of antiretroviral therapy (ART) has reduced the morbidity and mortality associated with HIV, adversely leading to the emergence of HIV drug resistance (HIVDR). In this study we aim to evaluate the prevalence of HIVDR mutations in ART-naive HIV-1 infected patients from northern India.Design. Analysis was performed using Viroseq genotyping system based on sequencing of entire protease and two-thirds of the Reverse Transcriptase (RT) region ofpolgene.Results. Seventy three chronic HIV-1 infected ART naïve patients eligible for first line ART were enrolled from April 2006 to August 2008. In 68 patients DNA was successfully amplified and sequencing was done. 97% of HIV-1 strains belonged to subtype C, and one each to subtype A1 and subtype B. The overall prevalence of primary DRMs was 2.9% [2/68, 95% confidence interval (CI), 0.3%–10.2%]. One patient had a major RT mutation M184V, known to confer resistance to lamivudine, and another had a major protease inhibitor (PI) mutation D30N that imparts resistance to nelfinavir.Conclusion. Our study shows that primary HIVDR mutations have a prevalence of 2.9% among ART-naive chronic HIV-1 infected individuals.

scholarly journals Hydroxyurea Enhances the Activities of Didanosine, 9-[2-(Phosphonylmethoxy)ethyl]adenine, and 9-[2-(Phosphonylmethoxy)propyl]adenine against Drug-Susceptible and Drug-Resistant Human Immunodeficiency Virus Isolates

1999 ◽  
Vol 43 (8) ◽  
pp. 2046-2050 ◽  
Author(s):  
Sarah Palmer ◽  
Robert W. Shafer ◽  
Thomas C. Merigan
Keyword(s):  
Human Immunodeficiency Virus ◽  
Drug Resistant ◽  
Wild Type ◽  
Immunodeficiency Virus ◽  
Hiv Type 1 ◽  
Virus Isolates ◽  
Hiv 1

ABSTRACT We assessed the effects of hydroxyurea (HU) at a concentration of 50 μM on the in vitro activities of 2′,3′-dideoxyinosine (ddI), 9-[2-(phosphonylmethoxy)ethyl]adenine (PMEA), and 9-[2-(phosphonylmethoxy)propyl]adenine (PMPA) against a wild-type human immunodeficiency virus (HIV) type 1 (HIV-1) laboratory isolate and a panel of five well-characterized drug-resistant HIV isolates. Fifty micromolar HU significantly increased the activities of ddI, PMEA, and PMPA against both the wild-type and the drug-resistant HIV-1 isolates. In fixed combinations, both ddI and PMEA were synergistic with HU against wild-type and drug-resistant viruses.

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