Detection of Drug Resistance-Associated and Background Mutations in Human Immunodeficiency Virus Type 1 CRF01_AE Protease and Reverse Transcriptase Derived from Drug Treatment-Naive Patients Residing in Central Thailand

2009 ◽  
Vol 25 (6) ◽  
pp. 625-631 ◽  
Author(s):  
Wattana Auwanit ◽  
Panasda Isarangkura-Na-Ayuthaya ◽  
Dao Kasornpikul ◽  
Kazuyoshi Ikuta ◽  
Pathom Sawanpanyalert ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Drug Resistance ◽  
Drug Treatment ◽  
Reverse Transcriptase ◽  
Human Immunodeficiency Virus Type ◽  
Virus Type ◽  
Immunodeficiency Virus ◽  
Treatment Naïve ◽  
Central Thailand

scholarly journals Exploitation of the Low Fidelity of Human Immunodeficiency Virus Type 1 (HIV-1) Reverse Transcriptase and the Nucleotide Composition Bias in the HIV-1 Genome To Alter the Drug Resistance Development of HIV

2001 ◽  
Vol 75 (13) ◽  
pp. 5772-5777 ◽  
Author(s):  
Jan Balzarini ◽  
Maria-José Camarasa ◽  
Maria-Jesus Pérez-Pérez ◽  
Ana San-Félix ◽  
Sonsoles Velázquez ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Drug Resistance ◽  
Reverse Transcriptase ◽  
Human Immunodeficiency Virus Type ◽  
Virus Type ◽  
Resistance Development ◽  
Nucleotide Bias ◽  
Immunodeficiency Virus ◽  
Hiv 1

ABSTRACT The RNA genome of the lentivirus human immunodeficiency virus type 1 (HIV-1) is significantly richer in adenine nucleotides than the statistically equal distribution of the four different nucleotides that is expected. This compositional bias may be due to the guanine-to-adenine (G→A) nucleotide hypermutation of the HIV genome, which has been explained by dCTP pool imbalances during reverse transcription. The adenine nucleotide bias together with the poor fidelity of HIV-1 reverse transcriptase markedly enhances the genetic variation of HIV and may be responsible for the rapid emergence of drug-resistant HIV-1 strains. We have now attempted to counteract the normal mutational pattern of HIV-1 in response to anti-HIV-1 drugs by altering the endogenous deoxynucleoside triphosphate pool ratios with antimetabolites in virus-infected cell cultures. We showed that administration of these antimetabolic compounds resulted in an altered drug resistance pattern due to the reversal of the predominant mutational flow of HIV (G→A) to an adenine-to-guanine (A→G) nucleotide pattern in the intact HIV-1-infected lymphocyte cultures. Forcing the virus to change its inherent nucleotide bias may lead to better control of viral drug resistance development.

scholarly journals Prevalence of Drug Resistance in Human Immunodeficiency Virus Type 1-Infected Treatment-Naive Children in Pune, India

2014 ◽  
Vol 30 (3) ◽  
pp. 294-298 ◽  
Author(s):  
Mukesh Kumar ◽  
Sourav Sen ◽  
Rakesh K. Gupta ◽  
Devidas Chaturbhuj ◽  
Srikanth P. Tripathy ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Drug Resistance ◽  
Human Immunodeficiency Virus Type ◽  
Virus Type ◽  
Immunodeficiency Virus ◽  
Treatment Naïve

scholarly journals Suppression of Viremia and Evolution of Human Immunodeficiency Virus Type 1 Drug Resistance in a Macaque Model for Antiretroviral Therapy

2007 ◽  
Vol 81 (22) ◽  
pp. 12145-12155 ◽  
Author(s):  
Zandrea Ambrose ◽  
Sarah Palmer ◽  
Valerie F. Boltz ◽  
Mary Kearney ◽  
Kay Larsen ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Drug Resistance ◽  
Antiretroviral Therapy ◽  
Reverse Transcriptase ◽  
Human Immunodeficiency Virus Type ◽  
Virus Type ◽  
Immunodeficiency Virus ◽  
The Impact ◽  
Hiv 1

ABSTRACT Antiretroviral therapy (ART) in human immunodeficiency virus type 1 (HIV-1)-infected patients does not clear the infection and can select for drug resistance over time. Not only is drug-resistant HIV-1 a concern for infected individuals on continual therapy, but it is an emerging problem in resource-limited settings where, in efforts to stem mother-to-child-transmission of HIV-1, transient nonnucleoside reverse transcriptase inhibitor (NNRTI) therapy given during labor can select for NNRTI resistance in both mother and child. Questions of HIV-1 persistence and drug resistance are highly amenable to exploration within animals models, where therapy manipulation is less constrained. We examined a pigtail macaque infection model responsive to anti-HIV-1 therapy to study the development of resistance. Pigtail macaques were infected with a pathogenic simian immunodeficiency virus encoding HIV-1 reverse transcriptase (RT-SHIV) to examine the impact of prior exposure to a NNRTI on subsequent ART comprised of a NNRTI and two nucleoside RT inhibitors. K103N resistance-conferring mutations in RT rapidly accumulated in 2/3 infected animals after NNRTI monotherapy and contributed to virologic failure during ART in 1/3 animals. By contrast, ART effectively suppressed RT-SHIV in 5/6 animals. These data indicate that suboptimal therapy facilitates HIV-1 drug resistance and suggest that this model can be used to investigate persisting viral reservoirs.

scholarly journals Resistance to Nucleoside Analog Reverse Transcriptase Inhibitors Mediated by Human Immunodeficiency Virus Type 1 p6 Protein

2001 ◽  
Vol 75 (20) ◽  
pp. 9644-9653 ◽  
Author(s):  
Solange Peters ◽  
Miguel Muñoz ◽  
Sabine Yerly ◽  
Victor Sanchez-Merino ◽  
Cecilio Lopez-Galindez ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Drug Resistance ◽  
Reverse Transcriptase ◽  
Human Immunodeficiency Virus Type ◽  
Virus Type ◽  
Nucleoside Analog ◽  
Viral Protease ◽  
Immunodeficiency Virus ◽  
Hiv 1

ABSTRACT Resistance of human immunodeficiency virus type 1 (HIV-1) to antiretroviral agents results from target gene mutation within thepol gene, which encodes the viral protease, reverse transcriptase (RT), and integrase. We speculated that mutations in genes other that the drug target could lead to drug resistance. For this purpose, the p1-p6 gag -p6 pol region of HIV-1, placed immediately upstream ofpol, was analyzed. This region has the potential to alter Pol through frameshift regulation (p1), through improved packaging of viral enzymes (p6Gag), or by changes in activation of the viral protease (p6Pol). Duplication of the proline-rich p6Gag PTAP motif, necessary for late viral cycle activities, was identified in plasma virus from 47 of 222 (21.2%) patients treated with nucleoside analog RT inhibitor (NRTI) antiretroviral therapy but was identified very rarely from drug-naı̈ve individuals. Molecular clones carrying a 3-amino-acid duplication, APPAPP (transframe duplication SPTSPT in p6Pol), displayed a delay in protein maturation; however, they packaged a 34% excess of RT and exhibited a marked competitive growth advantage in the presence of NRTIs. This phenotype is reminiscent of the inoculum effect described in bacteriology, where a larger input, or a greater infectivity of an organism with a wild-type antimicrobial target, leads to escape from drug pressure and a higher MIC in vitro. Though the mechanism by which the PTAP region participates in viral maturation is not known, duplication of this proline-rich motif could improve assembly and packaging at membrane locations, resulting in the observed phenotype of increased infectivity and drug resistance.

scholarly journals Drug Resistance Mutations in the Nucleotide Binding Pocket of Human Immunodeficiency Virus Type 1 Reverse Transcriptase Differentially Affect the Phosphorolysis-Dependent Primer Unblocking Activity in the Presence of Stavudine and Zidovudine and Its Inhibition by Efavirenz

2005 ◽  
Vol 49 (1) ◽  
pp. 342-349 ◽  
Author(s):  
Emmanuele Crespan ◽  
Giada A. Locatelli ◽  
Reynel Cancio ◽  
Ulrich Hübscher ◽  
Silvio Spadari ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Drug Resistance ◽  
Reverse Transcriptase ◽  
Human Immunodeficiency Virus Type ◽  
Virus Type ◽  
Nucleotide Binding ◽  
Binding Pocket ◽  
Immunodeficiency Virus ◽  
Hiv 1

ABSTRACT Human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT) derivatives with D113E, Y115F, F116Y, Q151E/N, and M184V mutations were studied for their phosphorolysis-mediated resistance to the nucleoside RT inhibitors (NRTIs) zidovudine and stavudine and for their inhibition by the nonnucleoside analogs (NNRTIs) efavirenz and nevirapine. The results presented here indicate that these single amino acid substitutions within the nucleotide binding pocket of the viral RT can independently affect different enzymatic properties, such as catalytic efficiency, drug binding, and phosphorolytic activity. Moreover, small local alterations of the physicochemical properties of the microenvironment around the active site can have profound effects on some NRTIs while hardly affecting other ones. In conclusion, even though different mutations within the nucleotide binding pocket of HIV-1 RT can result in a common phenotype (i.e., drug resistance), the molecular mechanisms underlying this phenotype can be very different. Moreover, the same mutation can give rise to different phenotypes depending on the nature of the substrates and/or inhibitors.

Sign in / Sign up

Export Citation Format

Share Document