Prevalence of Drug‐Resistant Human Immunodeficiency Virus Type 1 in Therapy‐Naive Patients and Usefulness of Genotype Testing

Ibe, Shiro; Hotta, Naoe; Takeo, Uta; Tawada, Yukio; Mamiya, Naoto; Yamanaka, Katsuo; Utsumi, Makoto; Kaneda, Toshio

doi:10.1111/j.1348-0421.2003.tb03411.x

Cited by 12 publications

(3 citation statements)

References 18 publications

(10 reference statements)

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“…Such variants cannot form major populations in viral quasi-species when acquired mutations cause severe damage to replicative fitness. Drug-resistant HIV-1, however, has been found in 6% of therapynaïve patients at our hospital (7). Assessment of replicative fitness has thus become important for understanding the survival activity of drug-resistant HIV-1 found in therapy-naïve patients.…”

Section: Discussionmentioning

confidence: 99%

Quantitative SNP‐Detection Method for Estimating HIV‐1 Replicative Fitness: Application to Protease Inhibitor‐Resistant Viruses

Ibe

Fujisaki

et al. 2006

Microbiology and Immunology

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We have improved the methods for the standard competitive growth assay of human immunodeficiency virus type 1 (HIV‐1). The cloning step for the mixed viral population and subsequent genotype analysis for arbitrary numbers of clones were excluded from procedures. Instead, a single nucleotide polymorphism (SNP)‐detection step was devised for the determination of viral populations. The quantitative SNP‐detection method can rapidly estimate the proportion of wild‐type and mutant populations with high reproducibility. Consequently, this method allows manipulation of many samples within a short period. Using this new competitive growth assay, replicative fitness of drug‐resistant HIV‐1 containing an M46I amino acid mutation in the protease was assessed in the presence or absence of indinavir. Without indinavir, replicative fitness of wild‐type HIV‐1 surpassed that of M46I‐mutated HIV‐1, and the fraction of mutated virus was reduced to about 10% at passage #9. In contrast, the fraction of M46I‐mutated virus increased to >90% at passage #5 in the presence of 26.4 nM indinavir. Almost identical results were obtained for L90M‐mutated HIV‐1 with or without saquinavir. HIV‐1 can survive under indinavir pressure by acquiring M46I mutation, as with acquisition of the L90M mutation under saquinavir pressure. However, these mutations damage viral replicative fitness under natural conditions without any drugs. Subtle differences between wild‐type and mutant viruses are thus easily detected using the improved method.

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Section: Discussionmentioning

confidence: 99%

Quantitative SNP‐Detection Method for Estimating HIV‐1 Replicative Fitness: Application to Protease Inhibitor‐Resistant Viruses

Ibe

Fujisaki

et al. 2006

Microbiology and Immunology

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“…This domain was not only conserved, but duplicated within some mother D sequences. It has been shown that duplication of this domain could be linked to antiretroviral drug resistance [ 54 , 55 , 64 ]. However since mother D has not been exposed to antiretroviral drugs (Table 1 ), this duplication must have arisen naturally or was present in the virus that was initially transmitted to mother D. It is not known at this point, however, what effect this duplication would have on the budding ability of the virus.…”

Section: Discussionmentioning

confidence: 99%

Molecular characterization of the HIV-1 gagnucleocapsid gene associated with vertical transmission

et al. 2006

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Background: The human immunodeficiency virus type 1 (HIV-1) nucleocapsid (NC) plays a pivotal role in the viral lifecycle: including encapsulating the viral genome, aiding in strand transfer during reverse transcription, and packaging two copies of the viral genome into progeny virions. Another gag gene product, p6, plays an integral role in successful viral budding from the plasma membrane and inclusion of the accessory protein Vpr within newly budding virions. In this study, we have characterized the gag NC and p6 genes from six mother-infant pairs following vertical transmission by performing phylogenetic analysis and by analyzing the degree of genetic diversity, evolutionary dynamics, and conservation of functional domains.

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“…Genotypic drug resistance testing of HIV-1 was performed according to our previously reported methods. 12,13 CNS adverse effects CNS symptoms were assessed using a psychiatric interview and the Symptom Check List-90-Revised (SCL-90-R) questionnaire, a widely used scale in psychopathology. 14 Upon initiation of EFV containing therapy, we thoroughly explained CNS adverse effects of EFV to patients.…”

Section: Efv Plasma Level and Genotypic Drug Resistance Testingmentioning

confidence: 99%

No Observable Correlation between Central Nervous System Side Effects and EFV Plasma Concentrations in Japanese HIV Type 1-Infected Patients Treated with EFV Containing HAART

Takahashi

Ibe

Kudaka

et al. 2007

AIDS Research and Human Retroviruses

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The present study assessed the relationship between central nervous system (CNS) side effects and plasma concentrations of efavirenz (EFV) in Japanese HIV-1-infected patients. Subjects consisted of 69 HIV-1-infected patients (57 therapy-naive and 12 therapy-experienced patients) being treated using EFV in combination with other antiretroviral agents at the outpatient HIV clinic. Successful virological treatment was achieved in 61 patients. Eight patients discontinued EFV containing therapy because CNS symptoms did not resolve (four patients), EFV-specific mutations were detected (two patients), or skin rash was observed (two patients). Mean EFV plasma concentration for 61 effectively treated patients, measured at 15 h postdosing, was 2.42 microg/ml (range: 0.78-6.82 microg/ml). This EFV concentration range contributed to suppressed viral load in these Japanese patients. Adverse CNS effects were observed in 19 patients soon after therapy onset. These effects disappeared within 1 month except for four patients who suffered severe CNS side effects. Mean EFV plasma concentrations were not significantly different between subjects with (2.45 +/- 1.08 microg/ml) and without (2.42 +/- 1.40 microg/ml) CNS side effects. We concluded no correlation existed between the plasma EFV concentration and the emergence of CNS side effects in Japanese HIV-1-infected patients. Further investigations, enforced with the drug concentration measurement at earlier time points and more appropriate assessment of CNS symptoms, are required.

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Prevalence of Drug‐Resistant Human Immunodeficiency Virus Type 1 in Therapy‐Naive Patients and Usefulness of Genotype Testing

Cited by 12 publications

References 18 publications

Quantitative SNP‐Detection Method for Estimating HIV‐1 Replicative Fitness: Application to Protease Inhibitor‐Resistant Viruses

Quantitative SNP‐Detection Method for Estimating HIV‐1 Replicative Fitness: Application to Protease Inhibitor‐Resistant Viruses

Molecular characterization of the HIV-1 gagnucleocapsid gene associated with vertical transmission

No Observable Correlation between Central Nervous System Side Effects and EFV Plasma Concentrations in Japanese HIV Type 1-Infected Patients Treated with EFV Containing HAART

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