[Show abstract][Hide abstract] ABSTRACT: Integrase inhibitors are recently prescribed to multi-class drug resistant HIV-1 patients in Hong Kong. Unlike pol gene, there are no FDA-approved genotypic resistance tests available for int. Limited studies compared the performance between an in-house and commercial integrase genotyping system. Information on baseline polymorphisms was also insufficient in our region.
To compare integrase genotyping data obtained from an in-house and ViroSeq™ Integra48 assay, and to illustrate integrase polymorphisms on HIV-1 B and non-B subtypes in Hong Kong.
A total of 283 HIV-1 patients were recruited during 2006-2012 in Hong Kong. All samples were genotyped by an in-house assay for pol and int separately, and 46 of them were further genotyped by ViroSeq™ Integra48. Polymorphisms and resistance mutations were analyzed by Stanford HIV Drug Resistance Database.
The included patients were mainly infected by HIV-1 subtype B (38.9%) and CRF01_AE (43.1%), followed by CRF07_BC (5.3%), C (3.9%), CRF02_AG (2.8%), D (1.4%), CRF08_BC (1.1%) or others (3.5%). Of 46 samples genotyped by ViroSeq™ and the in-house assays, all major and minor resistance mutations were concordant. Integrase major resistance mutations were identified in two CRF01_AE raltegravir-treated patients. Integrase minor resistance mutations were observed in subtypes B and CRF01_AE.
With 25% of the commercial cost, the in-house integrase genotyping assay managed to regenerate over 96% concordant results as good as the RUO ViroSeq™ assay. Further investigations are required to understand the effect on integrase minor mutations, which are present in many subtype B and CRF01_AE samples.
Journal of clinical virology: the official publication of the Pan American Society for Clinical Virology 07/2013; · 3.12 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The men-having-sex-with-men (MSM) population has become one of the major risk groups for HIV-1 infection in the Asia Pacific countries. Hong Kong is located in the centre of Asia and the transmission history of HIV-1 subtype B transmission among MSM remained unclear. The aim of this study was to investigate the transmission dynamics of HIV-1 subtype B virus in the Hong Kong MSM population. Samples of 125 HIV-1 subtype B infected MSM patients were recruited in this study. Through this study, the subtype B epidemic in the Hong Kong MSM population was identified spreading mainly among local Chinese who caught infection locally. On the other hand, HIV-1 subtype B infected Caucasian MSM caught infection mainly outside Hong Kong. The Bayesian phylogenetic analysis also indicated that 3 separate subtype B epidemics with divergence dates in the 1990s had occurred. The first and latest epidemics were comparatively small-scaled; spreading among the local Chinese MSM while sauna-visiting was found to be the major sex partner sourcing reservoir for the first subtype B epidemic. However, the second epidemic was spread in a large-scale among local Chinese MSM with a number of them having sourced their sex partners through the internet. The epidemic virus was estimated to have a divergence date in 1987 and the infected population in Hong Kong had a logistic growth throughout the past 20 years. Our study elucidated the evolutionary and demographic history of HIV-1 subtype B virus in Hong Kong MSM population. The understanding of transmission and growth model of the subtype B epidemic provides more information on the HIV-1 transmission among MSM population in other Asia Pacific high-income countries.
PLoS ONE 01/2011; 6(9):e25286. · 3.53 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: HIV-1 group M strains are characterized into 9 pure subtypes and 48 circulating recombinant forms (CRFs). Recent studies have identified the presence of new HIV-1 recombinants in Hong Kong and their complexity continues to increase. This study aims to characterize the HIV-1 genetic diversity in Hong Kong. Phylogenetic analyses were performed by using HIV-1 pol sequences including protease and partial reverse transcriptase isolated from 1045 local patients in Hong Kong from 2003 to 2008. For the pol sequences with unassigned genotype, the evidence of recombination was determined by using sliding-window based bootscan plots and their env C2V3 region were also sequenced. Epidemiological background of these patients was further collected. The pol phylogenetic analyses highlighted the extent of HIV-1 genetic diversity in Hong Kong. Subtype B (450/1045; 43.1%) and CRF01_AE (469/1045; 44.9%) variants were clearly predominant. Other genotypes (126/1045; 12.1%) including 3 defined subtypes, 10 CRFs, 1 unassigned subtype and 33 recombinants with 11 different mosaic patterns were observed. Recombinants of subtype B and CRF01_AE were mainly found among local Chinese MSM throughout 2004 to 2008, while the CRF02_AG and subtype G recombinants were circulating among non-Chinese Asian population in Hong Kong through heterosexual transmission starting from 2008. Our study demonstrated the complex recombination of HIV-1 in Hong Kong and the need in developing surveillance system for tracking the distribution of new HIV-1 genetic variants.
PLoS ONE 01/2010; 5(8):e12198. · 3.53 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: With considerable capacity for genetic diversification, new HIV-1 genotypes have been reported over the years. Three HIV-1 isolates previously genotyped as B using gag and env sequences were completely sequenced and reanalyzed. Several amino acid mutations were found in vif, rev, and nef genes but not in gag or env sequences. These alterations have not previously been reported in Hong Kong. The investigation of phylogenetic relatedness revealed that a region of the vif of the studied Hong Kong isolates subtype B cluster contains several subtype D signature amino acid residues. Several unique mutations on vif in these three isolates were also identified.
AIDS research and human retroviruses 01/2010; 26(1):117-22. · 2.18 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Seventy-six Chinese male HIV patients were interviewed on their use of traditional Chinese medicine (TCM). All except one had undetectable viral load, 28 had already progressed to AIDS. Forty-five (59.2%) had used TCM--11 infrequently and 33 commonly. No specific TCM recipe was preferentially used, while a variety of herbal tea and other over-the-counter health products of TCM in origin were reported. A minority (28.9%) have consulted a TCM practitioner in the preceding 6 months. Most patients admitted using TCM for the treatment of minor ailments (60.0%) and general health maintenance (57.8%), while western medicine was chosen for the therapy of major medical illnesses. TCM did not seem to have significant influence on the conventional HAART in this cohort. Many used TCM at a time interval from HAART in order not to affect the latter's effectiveness.
AIDS and Behavior 08/2008; 12(4):637-42. · 3.49 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: We studied polymorphism of the HIV coreceptor CC chemokine receptor (CCR) 5 in 1099 Chinese adults residing in Hong Kong, including 785 HIV-negative healthy donors and 314 HIV-positive patients. Ten mutants in the CCR5 open reading frame were identified, 7 of which were nonsynonymous. The frequencies of these alleles did not show a significant difference between HIV patients and healthy controls. G106R, Delta32, R223Q, 299(FS), and S336I were cloned from prevalent mutant genes, and their effects on HIV infection were analyzed by a series of in vitro experiments to determine their transcription levels, expression levels, conformational changes, and HIV coreceptor function. R223Q is the most prevalent CCR5 mutant in ethnic Chinese, with a frequency of 0.046, which does not affect HIV infection in vitro, however. The S336I mutant also does not affect its transcription, expression, or HIV coreceptor function. Similar to 299(FS), the mutant G106R located in the third transmembrane domain results in diminished HIV coreceptor function in vitro through conformation changes in ECL2.
[Show abstract][Hide abstract] ABSTRACT: Total lymphocyte count (TLC) is a simple marker for monitoring HIV disease in resource-poor setting. A value of 1.2 x 10(9)l(-1) could be used as an independent criterion for starting antiretroviral treatment, since it is highly predictive of a low CD4 count warranting intervention.
Journal of Infection 02/2005; 50(1):66-7. · 4.07 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: A Nepalese heterozygous carrier of a CCR5 mutant, designated 118delF, was characterized. There was a 3 basepair deletion at 352-354 in the CCR5 open reading frame, resulting in the deletion of the phe-118 residue located in the third transmembrane domain. The mutant protein has retained antigen specificity near the third extra-cellular loop (ECL3), but that of ECL2 is markedly reduced. The mutation has also abrogated HIV co-receptor activity. Clinically, the HIV disease had progressed slowly.
AIDS 09/2004; 18(12):1729-32. · 6.41 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: We studied the temporal trend of late HIV diagnosis and its determinants in Hong Kong. Three surrogate markers were used to proxy late diagnosis: AIDS within 3 months of HIV diagnosis, CD4 < 200/microL at HIV, and diagnosis at hospital. From 1984 to 2000, 1530 nonperinatal HIV infections and 495 patients with AIDS were reported. Overall, 23.9% to 52.1% of the patients were late presenters according to the three surrogates. There was no improvement in late diagnosis in the highly active antiretroviral therapy (HAART) era (1997-2000) compared to the pre-HAART era (1984-1996). Gender, ethnicity, age, and HIV exposure category were significant factors of late diagnosis on univariate analysis. On multivariate analysis, a lower risk of late diagnosis per all 3 surrogates was observed in men having sex with men (ranges of adjusted odds ratio [OR] [95% confidence interval [CI], 0.32-0.67 [0.21-0.91]) whereas the reverse was found for patients 35 years of age or older (ranges of adjusted ORs [95% CI], 1.62-2.80 [1.30-3.60]). In addition, male gender and Chinese ethnicity were associated with higher chance of having CD4 < 200/microL at HIV. The persistent trend of late HIV diagnosis in Hong Kong deserves attention. Strategies targeting infected people to enhance early HIV testing are needed, especially for those with risk factors of late diagnosis.
AIDS PATIENT CARE and STDs 09/2003; 17(9):461-9. · 3.09 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: There have been limited studies on the potential role of methadone treatment in HIV prevention in Asia. Over an 8-week period, we assessed the profiles of drug-taking and HIV risk behaviors, and tried to identify their relationships with methadone adherence in 690 clients who attended Hong Kong's methadone treatment program. In the preceding month, 71% of respondents reported using drugs and two-thirds of those respondents who had injected drugs at some time in their lives injected then. Infrequent clients who attended methadone clinics <2 times in the previous week were twice more likely to have injected drugs in the last month and six times more likely to have >5 injections in the last week than frequent clinic attendees. Also, clients taking <60 mg methadone daily were twice more likely to have >5 injections in the last week than those taking > or = 60 mg methadone. The findings called for further studies on harm reduction programs for HIV prevention among drug users in Asian countries.