Publications (20)51.41 Total impact
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Article: Prevalence of Transmitted HIV Drug Resistance in Iran between 2010 and 2011.
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ABSTRACT: Drug-resistant (DR) HIV emerges during combined antiretroviral treatment (cART), creating concern about widespread transmission of DR-HIV as cART is expanded in resource-limited countries. The aim of this study was to determine the predominant HIV-1 subtypes and prevalence of transmitted DR mutations among antiretroviral-naïve patients in Iran. To monitor transmission of DR HIV, a threshold surveillance based on the world health organization (WHO) guidelines was implemented in Iran. For this HIVDR threshold surveillance study, blood samples were collected from 50 antiretroviral-naïve HIV-1-infected patients. Antiretroviral-resistant mutations were determined by sequencing HIV-1 protease, reverse transcriptase and integrase regions. The HIV-1 subtype was determined by sequencing the p17 and C2-V5 regions of the gag and env genes, respectively. Phylogenetic analyses of the sequenced regions revealed that 45 (95.7%) of 47 samples that were successfully obtained were CRF35_AD. The remaining two cases were subtype B (2.1%) and CRF01_AE (2.1%). Consistent results were obtained also from Env and Gag sequences. Regarding prevalence of transmitted DR viruses, two cases were found to harbor reverse transcriptase-inhibitor-resistant mutations (4.3%). In addition, although not in the WHO list for surveillance of transmitted mutations, 13 minor protease-inhibitor-resistant mutations listed in the International AIDS Society-USA panel of drug resistance mutations were found. No DR mutations were detected in the integrase region. Our study clarified that CRF35_AD is the major subtype among HIV-1-infected patients in Iran. According to the WHO categorization method of HIVDR threshold survey, the prevalence of transmitted drug resistant HIV in Iran was estimated as moderate (5-15%).PLoS ONE 01/2013; 8(4):e61864. · 4.09 Impact Factor -
Article: Molecular Epidemiology of HIV Type 1 Infection in Iran: Genomic Evidence of CRF35_AD Predominance and CRF01_AE Infection Among Individuals Associated with Injection Drug Use.
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ABSTRACT: Abstract To understand the molecular epidemiology of HIV-1 infection in Iran, we conducted the first study to analyze the genome sequence of Iranian HIV-1 isolates. For this cross-sectional study, we enrolled 10 HIV-1-infected individuals associated with injection drug use from Tehran, Shiraz, and Kermanshah. Near full-length genome sequences obtained from their plasma samples were used for phylogenetic tree and similarity plotting analyses. Among 10 isolates, nine were clearly identified as CRF35_AD and the remaining one as CRF01_AE. Interestingly, five of our Iranian CRF35_AD isolates made two clusters with 10 Afghan CRF35_AD isolates in a phylogenetic tree, indicating epidemiological connections among injection drug users in Iran and Afghanistan. In contrast, our CRF01_AE isolate had no genetic relationship with any other CRF01_AE isolates worldwide, even from Afghanistan. This study provides the first genomic evidence of HIV-1 CRF35_AD predominance and CRF01_AE infection among individuals associated with injection drug use in Iran.AIDS research and human retroviruses 08/2012; · 2.18 Impact Factor -
Article: Clinical significance of HIV reverse-transcriptase inhibitor-resistance mutations.
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ABSTRACT: In this article, we summarize recent knowledge on drug-resistance mutations within HIV reverse transcriptase (RT). Several large-scale HIV-1 genotypic analyses have revealed that the most prevalent nucleos(t)ide analog RT inhibitor (NRTI)-resistance mutation is M184V/I followed by a series of thymidine analog-associated mutations: M41L, D67N, K70R, L210W, T215Y/F and K219Q/E. Among non-nucleoside RT inhibitor (NNRTI)-resistance mutations, K103N was frequently observed, followed by Y181C and G190A. Interestingly, V106M was identified in HIV-1 subtype C as a subtype-specific multi-NNRTI-resistance mutation. Regarding mutations in the HIV-1 RT C-terminal region, including the connection subdomain and RNase H domain, their clinical impacts are still controversial, although their effects on NRTI and NNRTI resistance have been confirmed in vitro. In HIV-2 infections, the high prevalence of the Q151M mutation associated with multi-NRTI resistance has been frequently observed.Future Microbiology 03/2011; 6(3):295-315. · 3.82 Impact Factor -
Article: Cellular HIV-1 DNA levels in patients receiving antiretroviral therapy strongly correlate with therapy initiation timing but not with therapy duration.
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ABSTRACT: Viral reservoir size refers to cellular human immunodeficiency virus-1 (HIV-1) DNA levels in CD4(+) T lymphocytes of peripheral blood obtained from patients with plasma HIV-1-RNA levels (viral load, VL) maintained below the detection limit by antiretroviral therapy (ART). We measured HIV-1 DNA levels in CD4(+) lymphocytes in such patients to investigate their clinical significance. CD4(+) T lymphocytes were isolated from the peripheral blood of 61 patients with a VL maintained at less than 50 copies/ml for at least 4 months by ART and total DNA was purified. HIV-1 DNA was quantified by nested PCR to calculate the copy number per 1 million CD4(+) lymphocytes (relative amount) and the copy number in 1 ml of blood (absolute amount). For statistical analysis, the Spearman rank or Wilcoxon signed-rank test was used, with a significance level of 5%. CD4 cell counts at the time of sampling negatively correlated with the relative amount of HIV-1 DNA (median = 33 copies/million CD4(+) lymphocytes; interquartile range [IQR] = 7-123 copies/million CD4(+) lymphocytes), but were not correlated with the absolute amounts (median = 17 copies/ml; IQR = 5-67 copies/ml). Both absolute and relative amounts of HIV-1 DNA were significantly lower in six patients in whom ART was initiated before positive seroconversion than in 55 patients in whom ART was initiated in the chronic phase, as shown by Western blotting. CD4 cell counts before ART introduction were also negatively correlated with both the relative and absolute amounts of HIV-1 DNA. Only the relative amounts of HIV-1 DNA negatively correlated with the duration of VL maintenance below the detection limit, while the absolute amounts were not significantly correlated with this period. The amounts of cellular HIV-1 DNA in patients with VLs maintained below the detection limit by the introduction of ART correlated with the timing of ART initiation but not with the duration of ART. In addition, CD4(+) T lymphocytes, which were newly generated by ART, diluted latently infected cells, indicating that measurements of the relative amounts of cellular HIV-1 DNA might be underestimated.BMC Infectious Diseases 01/2011; 11:146. · 3.12 Impact Factor -
Article: Outbreak of infections by hepatitis B virus genotype A and transmission of genetic drug resistance in patients coinfected with HIV-1 in Japan.
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ABSTRACT: The major routes of hepatitis B virus (HBV) infection in Japan has been mother-to-child transmission (MTCT) and blood transfusion. However, HBV cases transmitted through sexual contact are increasing, especially among HIV-1-seropositive patients. To understand the molecular epidemiology of HBV in HBV/HIV-1 coinfection, we analyzed HBV genotypes and HIV-1 subtypes in HBV/HIV-1-coinfected patients at Nagoya Medical Center from 2003 to 2007. Among 394 HIV-1-infected Japanese men having sex with men (MSM) who were newly diagnosed during the study period, 31 (7.9%) tested positive for the hepatitis B virus surface antigen. HBV sequence analyses were successful in 26 cases, with 21 (80.7%) and 5 (19.3%) cases determined as genotypes A and C, respectively. Our finding that HBV genotype A was dominant in HIV-1-seropositive patients alerts clinicians to an alternative outbreak of HBV genotype A in the HIV-1-infected MSM population and a shift in HBV genotype from C to A in Japan. The narrow genetic diversity in genotype A cases suggests that genotype A has been recently introduced into the MSM population and that sexual contacts among MSM were more active than speculated from HIV-1 tree analyses. In addition, we found a lamivudine resistance mutation in one naïve case, suggesting a risk of drug-resistant HBV transmission. As genotype A infection has a higher risk than infection with other genotypes for individuals to become HBV carriers, prevention programs are urgently needed for the target population.Journal of clinical microbiology 01/2011; 49(3):1017-24. · 4.16 Impact Factor -
Article: Trends in transmitted drug-resistant HIV-1 and demographic characteristics of newly diagnosed patients: nationwide surveillance from 2003 to 2008 in Japan.
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ABSTRACT: The emergence and transmission of drug-resistant human immunodeficiency virus-1 (HIV-1) compromises antiretroviral treatment for HIV-1. Thus, testing for drug resistance is recommended at diagnosis and before initiating highly active antiretroviral treatment. We conducted an epidemiological study enrolling newly diagnosed patients between 2003 and 2008 in our nationwide surveillance network. In the 6-year study period, the prevalence of drug-resistant HIV-1 among 2573 patients, consisting mainly of Japanese men in their late-30s and infected through male-to-male sexual contacts, followed an increasing trend from 5.9% (16/273) in 2003 to 8.3% (50/605) in 2008. Nucleoside reverse transcriptase inhibitor-associated mutations predominated in each year, with T215 revertants being the most abundant. The predictive factor for drug-resistant HIV-1 transmission was subtype B (OR=2.36; p=0.004), and those for recent HIV-1 infection were male gender (OR=3.79; p=0.009), MSM behavior (OR=1.67; p=0.01), Japanese nationality (OR=2.31; p=0.008), and subtype B (OR=5.64; p<0.05). Continued activities are needed to raise awareness of the risks of HIV-1 infection and complications of drug-resistant strains. Continued surveillance is also needed to understand trends in the HIV-1 epidemic.Antiviral research 10/2010; 88(1):72-9. · 3.61 Impact Factor -
Article: HIV-2 CRF01_AB: first circulating recombinant form of HIV-2.
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ABSTRACT: Five HIV-2-seropositive cases were recently identified in Japan, outside the HIV-2 endemic area of West Africa. To clarify the molecular epidemiology of HIV-2 in Japan, we analyzed sequences of these cases in detail. HIV-2 genetic groups were determined by gag and env sequences. For suspected recombinant isolates, the genetic structure was determined by full-length genomic analyses. To understand the history and evolution of HIV-2 recombinant isolates, we estimated the time of most recent common ancestor by Bayesian Markov chain Monte Carlo method. Three isolates were determined as recombinants of groups A and B, and their mosaic genome structures were identical with that of 7312A, a recombinant isolate reported in 1990 from Côte d'Ivoire. Our 3 isolates and 7312A fulfilled the criteria for determining a circulating recombinant form (CRF). These isolates were verified by the Los Alamos HIV sequence database as the first CRF of HIV-2, HIV-2 CRF01_AB. The mean time of most recent common ancestor of CRF01_AB was estimated as between 1964 and 1973, several decades after the estimated emergence of HIV-2. We recently identified HIV-2 CRF01_AB cases in Japan. This ectopic observation of the virus outside its original endemic area suggests an ongoing global spread of HIV-2 CRF01_AB.JAIDS Journal of Acquired Immune Deficiency Syndromes 07/2010; 54(3):241-7. · 4.43 Impact Factor -
Article: [Current topics on drug-resistant HIV in Japan].
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ABSTRACT: The prevalence of drug-resistant HIV among newly diagnosed HIV/AIDS cases in Japan increased from 4.9% (14/288) to 9.1% (43/473) in recent five years. This strengthens the importance of continuous surveillance to understand the epidemiological nature of transmitted drug-resistant HIV in our country. Regarding multi-drug-resistance among on-treated cases, the prevalence was estimated to be less than 1.9% (51/2,715). Both an increased mortality rate (26%) and a high rate of uncontrolled viremia (26%) were observed in three-class-resistant cases. However, 26% of three-class-resistant cases were successful in their salvage therapies containing new antiretrovirals, darunavir, raltegravir, maraviroc, and etravirine.Nippon rinsho. Japanese journal of clinical medicine 03/2010; 68(3):476-9. -
Article: An 11-Year Surveillance of HIV Type 1 Subtypes in Nagoya, Japan.
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ABSTRACT: Abstract To monitor active HIV-1 transmission in Nagoya, Japan, we have been determining the subtypes of HIV-1 infecting therapy-naive individuals who have newly visited the Nagoya Medical Center since 1997. The subtypes were determined by phylogenetic analyses using the base sequences in three regions of the HIV-1 genes including gag p17, pol protease (PR) and reverse transcriptase (RT), and env C2V3. Almost all HIV-1 subtypes from 1997 to 2007 and 93% of all HIV-1 isolates in 2007 were subtype B. HIV-1 subtypes A, C, D, and F have been detected sporadically since 1997, almost all in Africans and South Americans. The first detected circulating recombinant form (CRF ) was CRF01_AE (11-year average annual detection rate, 7.7%). Only two cases of CRF02_AG were detected in 2006. A unique recombinant form (URF ) was first detected in 1998 and the total number of URFs reached 25 by year 2007 (average annual detection rate, 4.7%). Eleven of these 25 were detected from 2000 to 2005 and had subtypes AE/B/AE as determined by base sequencing of the gag p17, pol PR and RT, and env C2V3 genes (average annual detection rate, 3.7%). Unique subtype B has been detected in six cases since 2006. All 17 of these patients were Japanese. Other recombinant HIV-1s have been detected intermittently in eight cases since 1998. During the 11-year surveillance, most HIV-1s in Nagoya, Japan were of subtype B. We expect that subtype B HIV-1 will continue to predominate for the next several years. Active recombination between subtype B and CRF01_AE HIV-1 and its transmission were also shown.AIDS research and human retroviruses 02/2009; 25(1):15-21. · 2.18 Impact Factor -
Article: Analysis of near full-length genomic sequences of drug-resistant HIV-1 spreading among therapy-naïve individuals in Nagoya, Japan: amino acid mutations associated with viral replication activity.
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ABSTRACT: We analyzed a total of 12 near full-length genomes of drug-resistant HIV-1 spreading among therapy-naïve individuals in Nagoya, Japan. Genomes comprised seven protease inhibitor (PI)-resistant viruses possessing an M46I (n = 6) or L90M mutation (n = 1) and five non-nucleoside reverse transcriptase inhibitor-resistant viruses possessing a K103N mutation. All 12 viruses conserved both an H87Q mutation in the cyclophilin A-binding site of Gag p24 (capsid) and a T23N mutation in the cysteine-rich domain of Tat protein. PI-resistant viruses commonly possessed two cleavage site mutations in the p6(Pol)/protease of Pol polyprotein (F48L in p6(Pol)) and the anchor/core domains of Nef protein (L57V). These amino acid mutations represent candidates for enhancing replication activity of drug-resistant viruses and supporting expansion of such viruses in therapy-naïve individuals.AIDS research and human retroviruses 08/2008; 24(8):1121-5. · 2.18 Impact Factor -
Article: Trend of drug-resistant HIV type 1 emergence among therapy-naive patients in Nagoya, Japan: an 8-year surveillance from 1999 to 2006.
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ABSTRACT: We studied the emergence of drug-resistant human immunodeficiency virus type 1 (HIV-1) with major amino acid mutations in 402 therapy-naive patients at Nagoya Medical Center, Japan, between 1999 and 2006. The mean prevalence of drug-resistant HIV-1 was 6.7% (range, 2.3-10.0%; n = 27). HIV-1 variants with protease inhibitor (PI)-resistant mutations alone were most frequently found (3.5%, n = 14), followed by those with nonnucleoside reverse transcriptase inhibitor (NNRTI)-resistant mutations alone (1.7%, n = 7). Variants with nucleoside reverse transcriptase inhibitor (NRTI)-resistant mutations alone were sporadically found (1.0%, n = 4). A variant possessing both NRTI- and PI-resistant mutations was detected in one patient (0.2%) and a variant possessing both NNRTI- and PI-resistant mutations was identified in another patient (0.2%). In addition, another 17 variants (4.2%, n = 17) with only 215-revertant mutations (T215C/D/G/L/S) that can easily reconvert to the nucleoside analogue-associated mutation of T215Y/F were found. The 402 viruses were phylogenetically analyzed, revealing three independent clusters comprising PI-resistant variants with the M46I or L90M mutation, NNRTI-resistant variants with the K103N mutation, and 215-revertant variants. The PI-resistant and 215-revertant strains have been spreading since 2000, and the NNRTI-resistant strain has started spreading since 2003. The nature of the epidemic and information for successfully blocking the spread of drug-resistant HIV-1 were clarified in this study.AIDS Research and Human Retroviruses 02/2008; 24(1):7-14. · 2.25 Impact Factor -
Article: 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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ABSTRACT: 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.AIDS Research and Human Retroviruses 09/2007; 23(8):983-7. · 2.25 Impact Factor -
Article: Drug-resistant HIV-1 prevalence in patients newly diagnosed with HIV/AIDS in Japan.
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ABSTRACT: The increasing prevalence of drug-resistant HIV transmission has become a critical epidemic in the world today. Studies in developed countries reported 8-27% of newly diagnosed HIV/AIDS patients are infected by drug-resistant strains. To determine the prevalence of drug-resistant HIV-1 among newly diagnosed cases in Japan, eight HIV/AIDS clinical centers, three public health laboratories and the National Institute of Infectious Diseases conducted a nationwide survey. Between January 2003 and December 2004, 575 newly diagnosed HIV/AIDS patients with both acute and chronic infections were enrolled in the study. Twenty-three cases, including three recently infected patients, were infected with HIV-1 having major drug-resistance mutations, including M41L, D67N, L100I, K103N, V106A, M184I, M184V, L210W, and revertant mutations at the 215 codon in reverse transcriptase and M46I in protease encoding regions. In this newly diagnosed population, we also clarified the prevalence of hepatitis virus coinfection, which was 8.8% for HBV and 4.3% for HCV. In conclusion, the drug-resistant transmission rate was 4.0% in Japan. Although this rate is significantly lower than that of other developed countries, this rate almost reaches the threshold at which baseline genotypic resistance testing would be cost-effective for all infected persons before initiating therapy.Antiviral Research 08/2007; 75(1):75-82. · 4.30 Impact Factor -
Article: Performance and quality assurance of genotypic drug-resistance testing for human immunodeficiency virus type 1 in Japan.
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ABSTRACT: Highly active antiretroviral therapy (HAART) can suppress human immunodeficiency virus type 1 (HIV-1) replication and plasma HIV-1 to below detectable levels. However, HAART becomes ineffective when drug-resistant viruses emerge during HAART. Monitoring drug-resistance mutations in viruses is necessary for selecting new drugs or therapies effective at inhibiting such HIV-1 variants. Most laboratories in Japan perform the tests using in-house protocols. However, the quality of these tests has never been assessed. Our study assessing the accuracy and reliability of HIV-1 genotypic drug-resistance testing in 15 laboratories in Japan revealed that the quality was very high (97.3% accurate). The errors, though rare, were caused by human errors, poor electropherograms, and the use of inadequate primers. Here, we propose troubleshooting procedures to improve testing accuracy and reliability in Japan.Japanese journal of infectious diseases 06/2007; 60(2-3):113-7. · 1.49 Impact Factor -
Article: Quantitative SNP-detection method for estimating HIV-1 replicative fitness: application to protease inhibitor-resistant viruses.
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ABSTRACT: 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.Microbiology and Immunology 02/2006; 50(10):765-72. · 1.30 Impact Factor -
Article: Cloning of a novel gene for quinolone resistance from a transferable plasmid in Shigella flexneri 2b.
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ABSTRACT: A novel gene for quinolone resistance was cloned from a transferable plasmid carried by a clinical isolate of Shigella flexneri 2b that was resistant to fluoroquinolones. The plasmid conferred low-level resistance to quinolones on Escherichia coli HB101. The protein encoded by the gene showed 59% amino acid identity with Qnr.Antimicrobial Agents and Chemotherapy 03/2005; 49(2):801-3. · 4.84 Impact Factor -
Article: Delayed HIV-1 infection of CD4+ T lymphocytes from therapy-naïve patients demonstrated by quantification of HIV-1 DNA copy numbers.
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ABSTRACT: Measuring the amount of HIV-1 DNA in infected cells is important to estimate the size of the viral reservoir in patients. However, the clinical impact of the intracellular viral DNA level remains unclear. The present study examines the clinical significance of the HIV-1 DNA level in peripheral CD4+ T lymphocytes from 21 therapy-naïve patients. HIV-1 DNA levels in purified peripheral CD4+ T lymphocytes were measured by the real-time PCR method using the Roche LightCycler system that can detect 200 copies/10(6) cells. We detected intracellular HIV-1 DNA in 15 (71.4%) of 21 patients at levels ranging from 270 to 98,120 copies/10(6) CD4+ cells, with a median of 2,220 copies/10(6) cells. We also found HIV-1 DNA that was below the detection limit in the remaining 6 patients, although 8,800-150,000 copies/ml of HIV-1 RNA were detected in plasma. Circular HIV-1 DNA was not detected in 5 of 6 cases, suggesting that reverse transcription in CD4+ T lymphocytes of these cases was not active. Thus, delayed HIV-1 infection of CD4+ T lymphocytes was demonstrated in these patients. The level of HIV-1 DNA in peripheral CD4+ T lymphocytes indicates the clinical status of therapy-naïve patients.Microbiology and Immunology 02/2004; 48(10):767-72. · 1.30 Impact Factor -
Article: Prevalence of infection and genotypes of GBV-C/HGV among homosexual men.
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ABSTRACT: Since the discovery of GB virus-C (GBV-C) and hepatitis G virus (HGV), many studies have been performed. These viruses are now known to be parenterally, as well as sexually transmitted. A phylogenetic analysis also revealed that GBV-C has five major genotypes: type 1 predominates in West Africa, type 2 in Europe and the United States, type 3 in parts of Asia, type 4 in Southeast Asia, and type 5 in South Africa. Despite the number of reports so far, there have been few large-scale surveys of homosexual men to determine the prevalence of the GBV-C/HGV infections. We examined the levels of GBV-C/HGV viremia in 297 homosexual men who attended the Nagoya Lesbian and Gay Revolution held in Nagoya, Japan. Reverse transcription-polymerase chain reaction (RT-PCR)/nested PCR of the GBV-C/HGV 5 ' -non-coding region (NCR), and base sequence analyses showed that the infection rate was 12.5%, and genotypes in this population were classified into type 2 (32%) and type 3 (68%). None were classified as types 1, 4, or 5 in this study. Our results indicate that the GBV-C/HGV type 2 seen mainly in Europe and the US is spreading widely in Japan, especially in the Nagoya district.Microbiology and Immunology 02/2003; 47(10):759-63. · 1.30 Impact Factor -
Article: Selection of human immunodeficiency virus type 1 variants with an insertion mutation in the p6(gag) and p6(pol) genes under highly active antiretroviral therapy.
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ABSTRACT: We detected several types of human immunodeficiency virus type 1 (HIV-1) variants with an insertion mutation in the p6(gag)and p6(pol) genes in eight of twenty-two (36.4%) patients who possessed drug-resistant viruses under highly active antiretroviral therapy (HAART). It was characteristic that a conserved proline-rich motif "PTAPP" in the N-terminus of p6(gag) protein was completely or partially duplicated in all cases. Five among the eight cases were retrospectively investigated in terms of the occurrence of dynamic change in the gag gene between the inserted and wild-type HIV-1 in the course of HAART. The longitudinal analysis revealed the following: 1) The inserted-type viruses were selected over the wild-type during HAART in three cases in which the both types coexisted in the beginning of the therapy. 2) In two cases in which the inserted-type HIV-1 alone was detected before the beginning of HAART, the inserted-type HIV-1 alone was continuously detected during the therapy. The inserted-type HIV-1 was also detected in four of thirty-nine (10.3%) therapy-naive patients. However, the frequency of inserted-type HIV-1 detection in the HAART-receiving patients is significantly higher than that in the therapy-naive patients (P = 0.02). These results suggest that this type of insertion mutation is a polymorphism of the p6(gag) and p6(pol) genes, however, it consequently gave an advantage on proliferation and/or survival of the HIV-1 variant under the presence of antiretroviral drugs.Microbiology and Immunology 02/2003; 47(1):71-9. · 1.30 Impact Factor -
Article: Prevalence of drug-resistant human immunodeficiency virus type 1 in therapy-naive patients and usefulness of genotype testing.
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ABSTRACT: In the present study, we performed genotypic drug-resistance testing in 116 therapy-naive human immunodeficiency virus type 1 (HIV-1)-infected patients between 1999 and 2002 at Nagoya National Hospital, Japan. The prevalence of drug-resistant HIV-1 with one or more major mutations significantly increased from 5.3% (4/75) in 1999-2001 to 17.1% (7/41) in 2002 (P=0.05), suggesting the spread of drug-resistant HIV-1. We identified a patient who possessed a protease (PR) inhibitor-resistant HIV-1 with a major mutation consisting of L90M before the initiation of therapy. The patient was administered zidovudine, lamivudine, and efavirenz as highly active antiretroviral therapy (HAART), as PR inhibitors were excluded based on the result of the drug-resistance testing. The treatment succeeded in strongly suppressing the proliferation of drug-resistant HIV-1 and concomitantly increased CD4 cell counts. Thus, we conclude that drug-resistance testing prior to the initiation of therapy is important for therapy-naive patients to devise the optimum therapy regimen for each individual.Microbiology and Immunology 02/2003; 47(7):499-505. · 1.30 Impact Factor
Top co-authors
Top Journals
Institutions
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2012
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Tehran University of Medical Sciences
- Department of Virology
Tehrān, Ostan-e Tehran, Iran
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2007–2011
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National Hospital Organization Nagoya Medical Center
Nagoya-shi, Aichi-ken, Japan
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