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Nguyen L.T.,Ireland Vietnam Blood Borne Virus Initiative IVVI | Nguyen L.T.,University College Dublin | Gray E.,St Jamess Hospital | Gray E.,A+ Network | And 17 more authors.
Antiviral Therapy | Year: 2015

Background: The HCV NS3/4A serine protease inhibitors (PIs) boceprevir (BOC), telaprevir (TVR) and simeprevir (SMV) are approved for treatment of chronic hepatitis C infection in combination with pegylated interferon and ribavirin. The present study investigated the prevalence of HCV NS3 drug resistance mutations (DRMs) associated with HCV genotype-1-infected individuals at baseline and in viral breakthrough following BOC and TVR treatment. Methods: HCV genotype-1-infected individuals were enrolled in a multicentre, prospective outcomes study. The HCV NS3 viral protease was analysed for DRMs at baseline (n=164) and at viral breakthrough (n=18) following BOC/TVR treatment. Results: Viral NS3 protease subtype analysis showed 65.2% (107/164) were HCV subtype-1a and 34.8% (57/164) were HCV subtype-1b infections. Naturally occurring PI DRMs in NS3 (V36L, T54S, V55A, Q80K/R and I132V) were identified in 57.3% (94/164) cases at baseline. The NS3 Q80K polymorphism was found in 43/107 (40.2%) of HCV subtype-1a and exclusively in clade 1 (43/82; 52.4%) versus clade 2 viruses (0/25; 0%, P<10-6). The pretreatment I132V variant was found in 78.9% (45/57) of subtype-1b. Of 18 patients who had viral breakthrough, the majority was subtype-1a (77.8%, 14/18). BOC/TVR-associated DRMs were detected in 94.4% (17/18), of which 64.7% (11/17) emerged on-treatment. Conclusions: To ensure the most appropriate direct-acting antiviral-based treatment regimen is employed, baseline reporting of clade and resistance mutations for HCV subtype-1a using nucleotide sequence-based analysis is warranted prior to commencement of therapy. ©2015 International Medical Press.

Quu Q.P.,Ireland Vietnam Blood Borne Virus Initiative IVVI | Quu Q.P.,National Diagnostics | Dean J.,Ireland Vietnam Blood Borne Virus Initiative IVVI | Dean J.,National Diagnostics | And 14 more authors.
AIDS Research and Human Retroviruses | Year: 2012

In Vietnam, where an estimated 280,000 people will be HIV-positive by 2012, recommended antiretroviral regimens do not include more recently developed therapeutics, such as Integrase inhibitors (INI) and coreceptor antagonists. This study examined HIV-1 coreceptor tropism and INI drug resistance profiles, in parallel with CCR5 genotypes, in a cohort of 60 HIV-positive individuals from different regions of Vietnam. No evidence of INI resistance was detected. Some 40% of individuals had X4-tropic HIV-1, making them unsuitable for treatment with CCR5 antagonists. We identified a novel CCR5 variant-S272P-along with other, previously reported variants: G106R, C178R, W153C, R223Q, and S336I. Interestingly, CCR5 variants known to affect HIV-1 infectivity were observed only in individuals harboring X4-tropic virus. Together, this study presents valuable baseline information on HIV-1 INI resistance, coreceptor tropism, and CCR5 variants in HIV-positive individuals in Vietnam. This should help inform policy on the future use of novel antiretrovirals in Vietnam. © 2012, Mary Ann Liebert, Inc.

Dunford L.,Ireland Vietnam Blood Borne Virus Initiative IVVI | Dunford L.,University College Dublin | Carr M.J.,Ireland Vietnam Blood Borne Virus Initiative IVVI | Carr M.J.,University College Dublin | And 18 more authors.
PLoS ONE | Year: 2012

Hepatitis B (HBV) infection is endemic in Viet Nam, with up to 8.4 million individuals estimated to be chronically infected. We describe results of a large, multicentre seroepidemiological and molecular study of the prevalence of HBV infection and blood-borne viral coinfections in Viet Nam. Individuals with varying risk factors for infection (n = 8654) were recruited from five centres; Ha Noi, Hai Phong, Da Nang, Khanh Hoa and Can Tho. A mean prevalence rate of 10.7% was observed and levels of HBsAg were significantly higher in injecting drug users (IDUs) (17.4%, n = 174/1000) and dialysis patients (14.3%, n = 82/575) than in lower-risk groups (9.4%; p<0.001). Coinfection with HIV was seen in 28% of HBV-infected IDUs (n = 49/174) and 15.2% of commercial sex workers (CSWs; n = 15/99). HCV infection was present in 89.8% of the HBV-HIV coinfected IDUs (n = 44/49) and 40% of HBV-HIV coinfected CSWs (n = 16/40). Anti-HDV was detected in 10.7% (n = 34/318) of HBsAg positive individuals. Phylogenetic analysis of HBV S gene (n = 187) showed a predominance of genotype B4 (82.6%); genotypes C1 (14.6%), B2 (2.7%) and C5 (0.5%) were also identified. The precore mutation G1896A was identified in 35% of all specimens, and was more frequently observed in genotype B (41%) than genotype C (3%; p<0.0001). In the immunodominant 'a' region of the surface gene, point mutations were identified in 31% (n = 58/187) of sequences, and 2.2% (n = 4/187) and 5.3% (n = 10/187) specimens contained the major vaccine escape mutations G145A/R and P120L/Q/S/T, respectively. 368 HBsAg positive individuals were genotyped for the IL28B SNP rs12979860 and no significant association between the IL28B SNP and clearance of HBsAg, HBV viral load or HBeAg was observed. This study confirms the high prevalence of HBV infection in Viet Nam and also highlights the significant levels of blood-borne virus coinfections, which have important implications for hepatitis-related morbidity and development of effective management strategies. © 2012 Dunford et al.

Dean J.,Ireland Vietnam Blood Borne Virus Initiative IVVI | Dean J.,University College Dublin | Ta Thi T.H.,Ireland Vietnam Blood Borne Virus Initiative IVVI | Ta Thi T.H.,National Diagnostics | And 16 more authors.
AIDS Research and Human Retroviruses | Year: 2011

The prevalence of HIV-1 drug resistance mutations (DRMs) was determined for a cross-section of individuals (n=8654) in five centers across Vietnam (Hanoi, Hai Phong, Da Nang, Khanh Hoa, and Can Tho) between 2008 and 2009. Following serological screening for HIV infection, HIV-1 viral load was determined, using an in-house real-time reverse transcriptase polymerase chain reaction (RT-PCR) assay. Samples with quantifiable viral loads [all either commercial sex workers (CSW) or intravenous drug users (IDU)] underwent DRM analysis. Sequences were obtained for 92 treatment-naive individuals, the majority of whom were infected with HIV-1 CRF01-AE (99%), with one instance of subtype A1 also detected. DRMs were detected in seven treatment-naive individuals (7.6%). The most common DRMs observed were M184V, V75A/M, M41L, and K65R (NRTI) and K103N, G190A, and Y181C (NNRTI). Overall, the data from this first multicenter survey of DRMs in Vietnam indicate that the problem of transmitted drug resistance is of major concern in the highest-risk groups of IDU and CSW. © 2011, Mary Ann Liebert, Inc.

Dunford L.,Ireland Vietnam Blood Borne Virus Initiative IVVI | Dunford L.,University College Dublin | Carr M.J.,Ireland Vietnam Blood Borne Virus Initiative IVVI | Carr M.J.,University College Dublin | And 28 more authors.
PLoS ONE | Year: 2012

Hepatitis C virus (HCV) is a genetically diverse pathogen infecting approximately 2-3% of the world's population. Herein, we describe results of a large, multicentre serological and molecular epidemiological study cataloguing the prevalence and genetic diversity of HCV in five regions of Vietnam; Ha Noi, Hai Phong, Da Nang, Khanh Hoa and Can Tho. Individuals (n = 8654) with varying risk factors for infection were analysed for the presence of HCV Ab/Ag and, in a subset of positive specimens, for HCV RNA levels (n = 475) and genotype (n = 282). In lower risk individuals, including voluntary blood donors, military recruits and pregnant women, the prevalence of infection was 0.5% (n = 26/5250). Prevalence rates were significantly higher (p<0.001) in intravenous drug users (IDUs; 55.6%, n = 556/1000), dialysis patients (26.6%, n = 153/575) commercial sex workers (CSWs; 8.7%, n = 87/1000), and recipients of multiple blood transfusions (6.0%, n = 32/529). The prevalence of HCV in dialysis patients varied but remained high in all regions (11-43%) and was associated with the receipt of blood transfusions [OR: 2.08 (1.85-2.34), p = 0.001], time from first transfusion [OR: 1.07 (1.01-1.13), p = 0.023], duration of dialysis [OR: 1.31 (1.19-1.43), p<0.001] and male gender [OR: 1.60 (1.06-2.41), p = 0.026]. Phylogenetic analysis revealed high genetic diversity, particularly amongst dialysis and multi-transfused patients, identifying subtypes 1a (33%), 1b (27%), 2a (0.4%), 3a (0.7%), 3b (1.1%), 6a (18.8%), 6e (6.0%), 6h (4.6%), 6l (6.4%) and 2 clusters of novel genotype 6 variants (2.1%). HCV genotype 1 predominated in Vietnam (60%, n = 169/282) but the proportion of infections attributable to genotype 1 varied between regions and risk groups and, in the Southern part of Vietnam, genotype 6 viruses dominated in dialysis and multi-transfused patients (73.9%). This study confirms a high prevalence of HCV infection in Vietnamese IDUs and, notably, reveals high levels of HCV infection associated with dialysis and blood transfusion. © 2012 Dunford et al.

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