Xiuqiong Bi

Prevalence of HBV infection among different HIV-risk groups in Hai Phong, Vietnam

Hepatitis B virus (HBV) infection in Hai Phong, northern Vietnam, was characterized by analyzing the prevalence and genotype distribution of HBV as well as co‐infection with human immunodeficiency virus type 1 (HIV‐1) among five different risk groups for HIV infection. Plasma samples were collected from intravenous drug users (n = 760, anti‐HIV‐1 antibody positive rate: 35.9%), female sex workers (FSWs; n = 91, 23.1%), seafarers (n = 94, 0%), pregnant women (n = 200, 0.5%), and blood donors (n = 210, 2.9%) in 2007 [Ishizaki et al. (2009): AIDS Res Hum Retroviruses 25:175–182]. Samples were screened for the hepatitis B surface antigen (HBsAg) and anti‐HBs antibody and analyzed genetically. The cumulative HBV incidence rate (HBsAg + anti‐HBs) was 53.2% (10.7 + 42.5%) in intravenous drug users, 51.6% (11.0 + 40.6%) in FSWs, 54.3% (9.6 + 44.7%) in seafarers, 50.5% (12.5 + 38.0%) in pregnant women, and 51.0% (18.1 + 32.9%) in blood donors; there was no significant difference among these groups. Of 163 HBsAg‐positive samples, 113 could be analyzed genetically. Phylogenetic analysis, based on the preS1 region, revealed genotype B4 was most prevalent (90/113; 79.6%), followed by C1 (17.7%), I1 (1.8%), and B2 (0.9%). There was no significant difference in HBV genotype distribution among different HIV infection‐risk groups. The prevalence of HBsAg was 10.3% (31/301) in HIV‐1‐infected individuals and 12.5% (132/1,054) in non‐HIV‐1‐infected individuals, which was not significant. In addition, no significant difference in HBV genotype distribution was observed between HBV/HIV‐1 co‐infected and HBV mono‐infected groups. These results suggest that, although HBV and HIV‐1 share modes of transmission, major transmission routes of HBV have been different from those of HIV‐1 in Hai Phong, Vietnam. J. Med. Virol. 83:399–404, 2011.

Characterization of HIV Type 1 Genotypes and Drug Resistance Mutations Among Drug-Naive HIV Type 1-Infected Patients in Northern Vietnam

To evaluate HIV-1 drug resistance-associated mutations among drug-naive HIV-1-infected patients in Northern Vietnam, we performed sequence analysis of HIV-1 pol-PR and pol-RT in samples collected from 206 (161 men and 45 women) consenting patients in 2008. From these 206 samples, we successfully sequenced 173 pol-PR and 155 pol-RT genes. Phylogenetic analysis revealed that all patients were infected with HIV-1 CRF01_AE. Major protease inhibitor resistance mutations, such as L33F, M46I, and M46L, were found in three patients (1.7%). Major reverse-transcriptase inhibitor (RTI) resistance mutations were found in seven patients (4.5%), four of whom had single mutations: A62V (nucleoside RTI resistance mutation) in two cases and K103N and Y181C (nonnucleoside RTI resistance mutation) in one case each. Three patients had multiple RTI resistance mutations: two, three, and seven, respectively. Thus, monitoring for drug-resistant HIV-1 and performing drug resistance testing before initiating antiretroviral therapy (ART) are recommended to facilitate selection of the appropriate ART and better clinical outcomes in Vietnam.

Infection with high-risk HPV types among female sex workers in northern Vietnam

Vaccines against two high‐risk human papillomavirus (HPV) types, HPV‐16, and HPV‐18, are in use currently, with high efficacy for preventing infections with these HPV types and consequent cervical cancers. However, circulating HPV types can vary with geography and ethnicity. The aim of this study was to investigate the prevalence of HPV types and the association between HPV types and abnormal cervical cytology among female sex workers in Northern Vietnam. Cervical swabs and plasma samples were collected from 281 female sex workers at two health centers in Hanoi and Hai Phong in 2009. The HPV L1 gene was amplified by PCR using original and modified GP5+/6+ primers. Amplified PCR products were genotyped by the microarray system GeneSquare (KURABO) and/or clonal sequencing. Of the 281 women, 139 (49.5%) were positive for HPV DNA. Among the HPV‐positive samples, 339 strains and 29 different types were identified. Multiple‐type and high risk‐type HPV infections were found in 85 (61.2%) and 124 (89.2%) women, respectively. The most common genotype was HPV‐52, followed by HPV‐16, HPV‐18, and HPV‐58. Abnormal cervical cytology was detected in 3.2% (9/281) of the women, and all of these samples were positive for HPV‐DNA. Age ≤25 years and infection with human immunodeficiency virus were associated positively with HPV infection among the women while ever smoking was associated negatively. These results show that HPV‐52 is most prevalent among female sex workers in Northern Vietnam, most of whom had normal cervical cytology. This information may be important for designing vaccination strategies in Vietnam. J. Med. Virol. 85:288–294, 2013.

Two-year outcome of first-line antiretroviral therapy among HIV-1 vertically-infected children in Hanoi, Vietnam.

A retrospective analysis of 86 HIV-1 vertically-infected Vietnamese children with a follow-up period >24 months after initiating antiretroviral therapy (ART) was performed from 2008 to 2012, to assess the outcome of first-line ART in resource-limited settings. Of the 86 children, 68 (79.1%) were treated successfully (plasma HIV-1 viral load [VL] <1000 copies/ml), and 63 (73.3%) had full viral suppression (VL <400 copies/ml) after 24 months of ART. No significant difference between successfully treated patients and failure groups was observed in VL, CD4+ T-cell count or clinical stage at baseline; age at ART start; or ART regimen. All 14 children with VL >5000 copies/ml, one of four children with VL 1000–5000 copies/ml and none with VL <1000 copies/ml developed reverse transcriptase inhibitor (RTI)-resistance mutations by 24 months of ART. Y181C and M184V/I were the most dominant non-nucleoside and nucleoside RTI-resistance mutations, respectively (13/15, 86.7%). These findings suggest that VL testing after 24 months of ART can be used to efficiently differentiate ART failures among HIV-1 vertically-infected children in resource-limited settings.

E6 and E7 variants of human papillomavirus‐16 and ‐52 in Japan, the Philippines, and Vietnam

Human papillomavirus (HPV) has several intragenotypic variants with different geographical and ethnic distributions. This study aimed to elucidate the distribution patterns of E6 and E7 (E6/E7) intragenotypic variants of HPV type 16 (HPV‐16), which is most common worldwide, and HPV‐52, which is common in Asian countries such as Japan, the Philippines, and Vietnam. In previous studies, genomic DNA samples extracted from cervical swabs were collected from female sex workers in these three countries and found to be positive for HPV‐16 or HPV‐52. Samples were amplified further for their E6/E7 genes using type‐specific primers and analyzed genetically. Seventy‐nine HPV‐16 E6/E7 genes were analyzed successfully and grouped into three lineages: European (Prototype), European (Asian), and African‐2. The prevalences of HPV‐16 European (Prototype)/European (Asian) lineages were 19.4%/80.6% (n = 31) in Japan, 75.0%/20.8% (n = 24) in the Philippines, and 0%/95.8% (n = 24) in Vietnam. The 109 HPV‐52 E6/E7 genes analyzed successfully were grouped into four lineages, A–D; the prevalences of lineages A/B/C/D were, respectively, 5.1%/92.3%/0%/2.6% in Japan (n = 39), 34.4%/62.5%/0%/3.1% in the Philippines (n = 32), and 15.8%/73.7%/7.9%/2.6% in Vietnam (n = 38). The distribution patterns of HPV‐16 and HPV‐52 lineages in these countries differed significantly (P < 0.000001 and P = 0.0048, respectively). There was no significant relationship between abnormal cervical cytology and either HPV‐16 E6/E7 lineages or specific amino acid mutations, such as E6 D25E, E6 L83V, and E7 N29S. Analysis of HPV‐16 and HPV‐52 E6/E7 genes can be a useful molecular‐epidemiological tool to distinguish geographical diffusion routes of these HPV types in Asia. J. Med. Virol. 85: 1069–1076, 2013.

Efficient monitoring of HIV-1 vertically infected children in Kenya on first-line antiretroviral therapy

BACKGROUND Worldwide access to antiretroviral therapy (ART) in low- and middle-income countries has significantly increased. Although this presents better treatment options for HIV-infected individuals, the challenge of monitoring ART in these settings still remains. OBJECTIVE To investigate efficient and cost-effective criteria for assessing ART failure among HIV-1-infected children on first-line ART in resource-limited settings. STUDY DESIGN Retrospective analysis of 75 HIV-1 vertically infected Kenyan children with a follow-up period of 24 months after initiating ART. Plasma viral load, peripheral CD4(+)T-cell counts and HIV-1 drug-resistance mutations were monitored biannually. RESULTS Plasma viral load (VL) was suppressed to undetectable level or more than 1.5 log(10) from baseline levels in 53 (70.7%) children within 24 months. VL in the remaining 22 (29.3%) children was not suppressed significantly. Of the 22 children, 21 were infected with HIV-1 strains that developed drug-resistance mutations; 9 within 12 months and 12 between 12 and 24 months. Among the 53 who were successfully treated, VL was suppressed in 33 within 12 months and in 20 between 12 and 24 months. There was no significant difference in VL at baseline and the change of CD4(+)T-cell counts after initiating ART between those treated successfully and the failure groups. CONCLUSION After initiating ART, children may require longer times to achieve complete viral suppression. Plasma viral load testing 24 months after initiating ART could be used to differentiate ART failures among HIV-1 vertically infected children in resource-limited settings. Additionally, drug resistance testing, if affordable, would be helpful in identifying those failing therapy and in choosing second-line regimens.

Discrepancies in prevalence trends for HIV, hepatitis B virus, and hepatitis C virus in Haiphong, Vietnam from 2007 to 2012

We previously reported a significant reduction in the prevalence of human immunodeficiency virus type 1 (HIV) from 2007 to 2012 in people who inject drugs (PWID; 35.9% to 18.5%, p < 0.001) and female sex workers (FSW; 23.1% to 9.8%, p < 0.05), but not in blood donors (BD) or pregnant women, in Haiphong, Vietnam. Our aim in the present study was to assess trends in the prevalence of infection with hepatitis B and C viruses (HBV and HCV, respectively). We also investigated the coinfection rates of HBV and HCV with HIV in the same groups. Between 2007 and 2012, HBV prevalence was significantly decreased in BD (18.1% vs. 9.0%, p = 0.007) and slightly decreased in FSW (11.0% vs. 3.9%, p = 0.21), but not in PWID (10.7% vs. 11.1%, p = 0.84). HCV prevalence was significantly decreased in PWID (62.1% in 2007 vs. 42.7% in 2008, p < 0.0001), but it had rebounded to 58.4% in 2012 (2008 vs. 2012, p < 0.0001). HCV prevalence also increased in FSW: 28.6% in 2007 and 2009 vs. 35.3% in 2012; however, this difference was not significant (2007 vs. 2012, p = 0.41). Rates of coinfection with HBV and HCV among HIV-infected PWID and FSW did not change significantly during the study period. Our findings suggest that the current harm reduction programs designed to prevent HIV transmission in PWID and FSW may be insufficient to prevent the transmission of hepatitis viruses, particularly HCV, in Haiphong, Vietnam. New approaches, such as the introduction of catch-up HBV vaccination to vulnerable adult populations and the introduction of HCV treatment as prevention, should be considered to reduce morbidity and mortality due to HIV and hepatitis virus coinfection in Vietnam.

Human papillomavirus infection in male patients with STI-related symptoms in Hanoi, Vietnam.

This cross‐sectional study investigated the prevalence, genotypes, and risk factors for human papillomavirus (HPV) infection in Hanoi, Vietnam. The study included 192 males (mean age, 32.9 years) with symptoms related to sexually transmitted infections (STI). Urinary, penile, and urethral samples were collected in April and May, 2014. HPV DNA was detected with PCR, performed with modified and/or original GP5+/GP6+ primers. HPV genotypes were determined with a gene array assay. Neisseria gonorrhoeae (NG) and Chlamydia trachomatis (CT) DNA were detected with loop‐mediated isothermal amplification. HPV DNA, NG, and CT were detected in 48 (25.0%), 23 (12.0%), and 41 (21.4%) patients, respectively. HPV DNA appeared in penile samples (21.0%, 39/186) more frequently than in urinary (3.1%, 6/191, P < 0.001) and urethral (9.4%, 18/192, P = 0.002) samples. Among patients with HPV, genotype prevalence was: HPV81 (22.9%),  HPV52 (18.8%), HPV18 (16.7%), and HPV16 (6.3%). Multiple‐type and high risk‐type HPV infections were determined in 33.3% and 64.6%, respectively. Multivariate analysis showed a significant association of HPV infection in urethra with younger sexual debut age. HPV52 was the most prevalent high‐risk HPV genotype, whereas HPV16 was less common in the male Vietnamese patients with STI‐related symptoms. Younger sexual‐debut age was a risk factor for HPV infection in urethra. J. Med. Virol. 88:1059–1066, 2016.

Impact of HIV Infection and Anti-Retroviral Therapy on the Immune Profile of and Microbial Translocation in HIV-Infected Children in Vietnam

CD4+ T-lymphocyte destruction, microbial translocation, and systemic immune activation are the main mechanisms of the pathogenesis of human immunodeficiency virus type 1 (HIV) infection. To investigate the impact of HIV infection and antiretroviral therapy (ART) on the immune profile of and microbial translocation in HIV-infected children, 60 HIV vertically infected children (31 without ART: HIV(+) and 29 with ART: ART(+)) and 20 HIV-uninfected children (HIV(−)) aged 2–12 years were recruited in Vietnam, and their blood samples were immunologically and bacteriologically analyzed. Among the HIV(+) children, the total CD4+-cell and their subset (type 1 helper T-cell (Th1)/Th2/Th17) counts were inversely correlated with age (all p < 0.05), whereas regulatory T-cell (Treg) counts and CD4/CD8 ratios had become lower, and the CD38+HLA (human leukocyte antigen)-DR+CD8+- (activated CD8+) cell percentage and plasma soluble CD14 (sCD14, a monocyte activation marker) levels had become higher than those of HIV(−) children by the age of 2 years; the CD4/CD8 ratio was inversely correlated with the plasma HIV RNA load and CD8+-cell activation status. Among the ART(+) children, the total CD4+-cell and Th2/Th17/Treg-subset counts and the CD4/CD8 ratio gradually increased, with estimated ART periods of normalization being 4.8–8.3 years, whereas Th1 counts and the CD8+-cell activation status normalized within 1 year of ART initiation. sCD14 levels remained high even after ART initiation. The detection frequency of bacterial 16S/23S ribosomal DNA/RNA in blood did not differ between HIV-infected and -uninfected children. Thus, in children, HIV infection caused a rapid decrease in Treg counts and the early activation of CD8+ cells and monocytes, and ART induced rapid Th1 recovery and early CD8+-cell activation normalization but had little effect on monocyte activation. The CD4/CD8 ratio could therefore be an additional marker for ART monitoring.

Positive correlation of HIV infection with Giardia intestinalis assemblage B but not with assemblage A in asymptomatic Kenyan children.

A cross-sectional molecular epidemiological study of Giardia intestinalis infection was conducted among asymptomatic Kenyan children with (n = 123) and without (n = 111) HIV infection. G. intestinalis assemblage B infection was positively correlated with HIV infection [HIV (+), 18.7% vs. HIV (−), 11.7%; P = 0.013], whereas assemblage A infection was not [HIV (+), 4.1% vs. HIV (−), 6.3%; P = 0.510]. Thus, HIV infection is a risk factor for G. intestinalis assemblage B infection but not for assemblage A infection.