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N348I in HIV-1 reverse transcriptase decreases susceptibility to tenofovir and etravirine in combination with other resistance mutations. 2010

Nicolas Sluis-Cremer, and Katie Moore, and Jessica Radzio, and Secondo Sonza, and Gilda Tachedjian
University of Pittsburgh School of Medicine, Department of Medicine, Pittsburgh, PA, USA.

We previously demonstrated that N348I in HIV-1 reverse transcriptase confers zidovudine and nevirapine resistance. However, both of these inhibitors are currently infrequently used in developed countries, and the impact of N348I on newer reverse transcriptase inhibitors, such as tenofovir and etravirine, is unknown. In this study, we demonstrate that N348I alone confers no resistance to tenofovir and low-level resistance to etravirine. However, N348I significantly decreases tenofovir susceptibility when combined with thymidine analogue mutations and etravirine susceptibility when combined with Y181C.

UI MeSH Term Description Entries
D009154 Mutation Any detectable and heritable change in the genetic material that causes a change in the GENOTYPE and which is transmitted to daughter cells and to succeeding generations. Mutations
D009570 Nitriles Organic compounds containing the -CN radical. The concept is distinguished from CYANIDES, which denotes inorganic salts of HYDROGEN CYANIDE. Nitrile
D011724 Pyridazines Six-membered rings with two adjacent nitrogen atoms also called 1,2-diazine.
D011743 Pyrimidines A family of 6-membered heterocyclic compounds occurring in nature in a wide variety of forms. They include several nucleic acid constituents (CYTOSINE; THYMINE; and URACIL) and form the basic structure of the barbiturates.
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000068698 Tenofovir An adenine analog REVERSE TRANSCRIPTASE INHIBITOR with antiviral activity against HIV-1 and HEPATITIS B. It is used to treat HIV INFECTIONS and CHRONIC HEPATITIS B, in combination with other ANTIVIRAL AGENTS, due to the emergence of ANTIVIRAL DRUG RESISTANCE when it is used alone. (R)-9-(2-phosphonylmethoxypropyl)adenine,9-(2-Phosphonomethoxypropyl)adenine,9-(2-Phosphonylmethoxypropyl)adenine,9-(2-Phosphonylmethoxypropyl)adenine, (+-)-isomer,9-(2-Phosphonylmethoxypropyl)adenine, (R)-isomer - T357098,9-(2-Phosphonylmethoxypropyl)adenine, (S)-isomer,9-PMPA (tenofovir),Tenofovir Disoproxil,Tenofovir Disoproxil Fumarate,Viread,Disoproxil Fumarate, Tenofovir,Disoproxil, Tenofovir,Fumarate, Tenofovir Disoproxil
D000225 Adenine A purine base and a fundamental unit of ADENINE NUCLEOTIDES. Vitamin B 4,4, Vitamin B,B 4, Vitamin
D015497 HIV-1 The type species of LENTIVIRUS and the etiologic agent of AIDS. It is characterized by its cytopathic effect and affinity for the T4-lymphocyte. Human immunodeficiency virus 1,HIV-I,Human Immunodeficiency Virus Type 1,Immunodeficiency Virus Type 1, Human
D015658 HIV Infections Includes the spectrum of human immunodeficiency virus infections that range from asymptomatic seropositivity, thru AIDS-related complex (ARC), to acquired immunodeficiency syndrome (AIDS). HTLV-III Infections,HTLV-III-LAV Infections,T-Lymphotropic Virus Type III Infections, Human,HIV Coinfection,Coinfection, HIV,Coinfections, HIV,HIV Coinfections,HIV Infection,HTLV III Infections,HTLV III LAV Infections,HTLV-III Infection,HTLV-III-LAV Infection,Infection, HIV,Infection, HTLV-III,Infection, HTLV-III-LAV,Infections, HIV,Infections, HTLV-III,Infections, HTLV-III-LAV,T Lymphotropic Virus Type III Infections, Human
D016297 Mutagenesis, Site-Directed Genetically engineered MUTAGENESIS at a specific site in the DNA molecule that introduces a base substitution, or an insertion or deletion. Mutagenesis, Oligonucleotide-Directed,Mutagenesis, Site-Specific,Oligonucleotide-Directed Mutagenesis,Site-Directed Mutagenesis,Site-Specific Mutagenesis,Mutageneses, Oligonucleotide-Directed,Mutageneses, Site-Directed,Mutageneses, Site-Specific,Mutagenesis, Oligonucleotide Directed,Mutagenesis, Site Directed,Mutagenesis, Site Specific,Oligonucleotide Directed Mutagenesis,Oligonucleotide-Directed Mutageneses,Site Directed Mutagenesis,Site Specific Mutagenesis,Site-Directed Mutageneses,Site-Specific Mutageneses

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