scholarly journals Impact of HIV‐1 Reverse Transcriptase Polymorphism F214L on Virological Response to Thymidine Analogue–Based Regimens in Antiretroviral Therapy (ART)–Naive and ART‐Experienced Patients

2007 ◽  
Vol 196 (8) ◽  
pp. 1180-1190 ◽  
Author(s):  
Francesca Ceccherini‐Silberstein ◽  
Alessandro Cozzi‐Lepri ◽  
Lidia Ruiz ◽  
Amanda Mocroft ◽  
Andrew N. Phillips ◽  
...  
Keyword(s):  
Antiretroviral Therapy ◽  
Reverse Transcriptase ◽  
Virological Response ◽  
Thymidine Analogue ◽  
Hiv 1

scholarly journals Impact of long-term antiretroviral therapy on gut and oral microbiotas in HIV-1-infected patients

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Mayumi Imahashi ◽  
Hirotaka Ode ◽  
Ayumi Kobayashi ◽  
Michiko Nemoto ◽  
Masakazu Matsuda ◽  
...  
Keyword(s):  
Antiretroviral Therapy ◽  
Reverse Transcriptase ◽  
Transcriptase Inhibitor ◽  
Strand Transfer ◽  
Intestinal Dysbiosis ◽  
Α Diversity ◽  
Reverse Transcriptase Inhibitor ◽  
Hiv 1 ◽  
Over Time

AbstractIn HIV-1-infected patients, antiretroviral therapy (ART) is a key factor that may impact commensal microbiota and cause the emergence of side effects. However, it is not fully understood how long-term ART regimens have diverse impacts on the microbial compositions over time. Here, we performed 16S ribosomal RNA gene sequencing of the fecal and salivary microbiomes in patients under different long-term ART. We found that ART, especially conventional nucleotide/nucleoside reverse transcriptase inhibitor (NRTI)-based ART, has remarkable impacts on fecal microbial diversity: decreased α-diversity and increased ß-diversity over time. In contrast, dynamic diversity changes in the salivary microbiome were not observed. Comparative analysis of bacterial genus compositions showed a propensity for Prevotella-enriched and Bacteroides-poor gut microbiotas in patients with ART over time. In addition, we observed a gradual reduction in Bacteroides but drastic increases in Succinivibrio and/or Megasphaera under conventional ART. These results suggest that ART, especially NRTI-based ART, has more suppressive impacts on microbiota composition and diversity in the gut than in the mouth, which potentially causes intestinal dysbiosis in patients. Therefore, NRTI-sparing ART, especially integrase strand transfer inhibitor (INSTI)- and/or non-nucleotide reverse transcriptase inhibitor (NNRTI)-containing regimens, might alleviate the burden of intestinal dysbiosis in HIV-1-infected patients under long-term ART.

scholarly journals HIV‐1 Reverse Transcriptase Connection Domain Mutations: Dynamics of Emergence and Implications for Success of Combination Antiretroviral Therapy

2010 ◽  
Vol 51 (5) ◽  
pp. 620-628 ◽  
Author(s):  
Viktor von Wyl ◽  
Maryam Ehteshami ◽  
Lisa M. Demeter ◽  
Philippe Bürgisser ◽  
Monique Nijhuis ◽  
...  
Keyword(s):  
Antiretroviral Therapy ◽  
Reverse Transcriptase ◽  
Combination Antiretroviral Therapy ◽  
Hiv 1

Presence of numerous stop codons in HIV-1 reverse transcriptase proviral DNA sequences from patients with virological response to HAART

AIDS ◽  
2006 ◽  
Vol 20 (9) ◽  
pp. 1327-1329 ◽  
Author(s):  
Alain Makinson ◽  
Bernard Masquelier ◽  
Audrey Taieb ◽  
Gilles Peytavin ◽  
Anne Waldner-Combernoux ◽  
...  
Keyword(s):  
Reverse Transcriptase ◽  
Dna Sequences ◽  
Virological Response ◽  
Stop Codons ◽  
Proviral Dna ◽  
Hiv 1

scholarly journals Thymidine Analogue Excision and Discrimination Modulated by Mutational Complexes Including Single Amino Acid Deletions of Asp-67 or Thr-69 in HIV-1 Reverse Transcriptase

2011 ◽  
Vol 286 (23) ◽  
pp. 20615-20624 ◽  
Author(s):  
Mónica Kisic ◽  
Tania Matamoros ◽  
María Nevot ◽  
Jesús Mendieta ◽  
Javier Martinez-Picado ◽  
...  
Keyword(s):  
Amino Acid ◽  
Reverse Transcriptase ◽  
Single Amino Acid ◽  
Thymidine Analogue ◽  
Hiv 1

scholarly journals Chain-Terminating Dinucleoside Tetraphosphates Are Substrates for DNA Polymerization by Human Immunodeficiency Virus Type 1 Reverse Transcriptase with Increased Activity against Thymidine Analogue-Resistant Mutants

2006 ◽  
Vol 50 (11) ◽  
pp. 3607-3614 ◽  
Author(s):  
Peter R. Meyer ◽  
Anthony J. Smith ◽  
Suzanne E. Matsuura ◽  
Walter A. Scott
Keyword(s):  
Human Immunodeficiency Virus ◽  
Reverse Transcriptase ◽  
Human Immunodeficiency Virus Type ◽  
Virus Type ◽  
Thymidine Analogue ◽  
Immunodeficiency Virus ◽  
Dna Chain ◽  
Resistant Mutants ◽  
Hiv 1

ABSTRACT Nucleoside reverse transcriptase inhibitors are an important class of drugs for treatment of human immunodeficiency virus type 1 (HIV-1) infection. Resistance to these drugs is often the result of mutations that increase the transfer of chain-terminating nucleotides from blocked DNA termini to a nucleoside triphosphate acceptor, resulting in the generation of an unblocked DNA chain and synthesis of a dinucleoside polyphosphate containing the chain-terminating deoxynucleoside triphosphate analogue. We have synthesized and purified several dinucleoside tetraphosphates (ddAp4ddA, ddCp4ddC, ddGp4ddG, ddTp4ddT, Ap4ddG, 2′(3′)-O-(N-methylanthraniloyl)-Ap4ddG, and AppNHppddG) and show that these compounds can serve as substrates for DNA chain elongation and termination resulting in inhibition of DNA synthesis. Thymidine analogue-resistant mutants of reverse transcriptase are up to 120-fold more sensitive to inhibition by these compounds than is wild-type enzyme. Drugs based on the dinucleoside tetraphosphate structure could delay or prevent the emergence of mutants with enhanced primer unblocking activity. In addition, such drugs could suppress the resistance phenotype of mutant HIV-1 that is present in individuals infected with resistant virus.

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