Introduction Incident syphilis leads to changes in plasma HIV-1 RNA and CD4 + T-cell level in people with HIV (PWH) with viraemia. Its effect in PWH on suppressive antiretroviral therapy (ART) is less clear. Methods PWH on suppressive ART (plasma HIV-1 RNA < 50copies/mL) followed at the Queen Elizabeth Hospital, Hong Kong, China were regularly screened for syphilis. Their plasma HIV-1 RNA, CD4 + and CD8 + T-cell, and total lymphocyte levels before syphilis, during syphilis, and after successful treatment were compared. Results Between 2005 and 2020, 288 syphilis episodes from 180 individuals were identified; 287 episodes were related to male, with a median age of 41 at diagnosis; 221 (77%) were syphilis re-infection. The rates of plasma HIV-1 suppression were statistically unchanged across the time-points (97% pre-syphilis, 98% during syphilis, and 99% post-treatment). Total lymphocyte, CD4+ and CD8+ T-cell levels decreased during incident syphilis (p<0.01), and rebounded post-treatment (p<0.01). VDRL titre was associated with declines in CD4+ T-cell (p=0.045), CD8+ T-cell (p=0.004), and total lymphocyte levels (p=0.021). Pre-syphilis CD4/CD8 ratio was associated with increases in CD8+ T-cell (p=0.001) and total lymphocyte levels (p=0.046) during syphilis. Syphilis re-infection was associated with an increase in total lymphocyte level (p=0.037). In the multivariable analysis, only pre-syphilis CD4/CD8 ratio was independently associated with increases in CD8+ T-cell (p=0.014) and total lymphocyte levels (p=0.039) during syphilis. Conclusions Among virally-suppressed PWH, total lymphocyte, CD4+, and CD8+ T-cell levels declined during incident syphilis but rebounded post-treatment. The status of plasma HIV suppression was unaffected by syphilis.

Objective: To give an overview and update on central nervous system inflammatory demyelinating diseases in Hong Kong. Findings: Using retrospective analysis of records from the Multiple Sclerosis (MS) Specialist Panel, the prevalence of MS in Hong Kong was estimated to be 6.9 per 100,000, while the annual incidence were 0.86 (SD = 0.135, 95% CI = 0.76 to 0.96) and 0.16 (SD = 0.11, 95% CI = 0.08-0.23) per 100,000 for adult and pediatric populations, respectively. Preliminary data from the Hong Kong MS Society's NMOSD (neuromyelitis optica spectrum disorders) Registry showed that the local prevalence of NMOSD was 3.3 per 100 000, with a seropositivity rate of 80%. MS and NMOSD both had a female preponderance, and MS had younger disease onset age. NMOSD patients had more long-term disability in terms of EDSS (expanded disability status scale) but MS patients had more cognitive impairment. Radiological features that discriminated MS and NMOSD were similar to other populations, and brain atrophy was observed in both diseases. The number of available treatment options for MS in Hong Kong has greatly increased in the past decade, including injectables, oral disease-modifying agents, and immune-reconstitution therapies. For NMOSD, corticosteroids and oral immunosuppressants were the mainstay of treatment. Summary: The updated prevalence of MS and NMOSD in Hong Kong was higher than previously reported, and comparable with other Asian countries. The clinical, laboratory and imaging features of MS and NMOSD in Hong Kong were similar to those in neighboring regions.

HIV-associated neurocognitive disorder (HAND) remains prevalent in the era of combination antiretroviral therapy (cART). The prevalence of HAND in Hong Kong is not known.

Background There are no data on neutralising antibodies to interferon-beta and its clinical implications in Chinese patients with multiple sclerosis (MS). Objectives The objectives of this study were to investigate the prevalence of neutralising antibodies among Chinese patients with relapsing MS receiving interferon-beta (1a or 1b) and to study the association between neutralising antibodies and the clinical-radiological response. Methods We performed a cross-sectional study on MS patients who received interferon-beta for 9 months or more, and evaluated the clinical response by relapses and magnetic resonance imaging lesions. Blood samples were evaluated for myxovirus resistance protein A (MxA) gene expression by polymerase chain reaction, anti-interferon-beta binding antibodies by enzyme-linked immunosorbent assay, and neutralising antibodies by cell-based MxA protein induction and luciferase reporter gene assays. Assay performances were evaluated by receiver operating characteristic analysis. Results Among 78 subjects recruited, 61/77 (79%) had anti-interferon-beta binding antibodies, and 22/78 (28%) had neutralising antibodies by MxA protein induction assay. The presence of high-titre neutralising antibodies was associated with poor clinical outcome (odds ratio 6.1, 95% confidence interval 1.5–25.6, P = 0.013). The sensitivity and specificity for neutralising antibodies using MxA gene expression assay (cut-off 0.20) was 80% and 68%, respectively (area under the curve 0.71). Conclusions Neutralising antibodies are associated with poor clinical outcome in Chinese patients with relapsing MS. MxA gene expression and protein induction assays are complimentary assays for neutralising antibody detection.

Objective: Employment is important for patients with chronic illness, and to remain employed is a robust support to them. This study aimed to examine the employment rate and to identify factors associated with employment among multiple sclerosis (MS) in Hong Kong.Methods: A cross-sectional study was performed from 2010 to 2011 at five major public hospitals. Fifty-nine clinical definite MS patients with no evidence of dementia (Mini-Mental State Examination >= 22) were recruited. Demographic data and neuropsychological test results including memory, visual perception, psychological well-being, motor, executive domain and processing speed were collected. Principal component analysis and logistic regression with multiple imputation were used in data analyses. Results: The employment rate among MS patients was 56%. Patients with better cognitive functions were more likely to be employed (p=0.002). No significant association was found between employment status and age, gender, level of education, types of MS, disease duration, frequency of relapse or use of interferon.Conclusion: MS patients had high unemployment rate (44%) which was 11.5 times higher than the general population in Hong Kong. MS patients with better cognitive functions had higher employment rates.

BACKGROUND:Influenza causes excessive hospitalizations and deaths. The study assessed the efficacy and safety of a clarithromycin-naproxen-oseltamivir combination for treatment of serious influenza. METHODS:From February to April 2015, we conducted a prospective open-label, randomized, controlled trial. Adult patients hospitalized for A(H3N2) influenza were randomly assigned to a 2-day combination of clarithromycin 500 mg, naproxen 200 mg, and oseltamivir 75 mg twice daily, followed by 3 days of oseltamivir or to oseltamivir 75 mg twice daily without placebo for 5 days as a control method (1:1). The primary end point was 30-day mortality. The secondary end points were 90-day mortality, serial nasopharyngeal aspirate (NPA) virus titer, percentage of neuraminidase-inhibitor-resistant A(H3N2) virus (NIRV) quasispecies, pneumonia severity index (PSI), and duration of hospital stay. RESULTS:Among the 217 patients with influenza A(H3N2) enrolled, 107 were randomly assigned to the combination treatment. The median age was 80 years, and 53.5% were men. Adverse events were uncommon. Ten patients died during the 30-day follow-up. The combination treatment was associated with lower 30-day mortality (P = .01), less frequent high dependency unit admission (P = .009), and shorter hospital stay (P < .0001). The virus titer and PSI (days 1-3; P < .01) and the NPA specimens with NIRV quasispecies ≥ 5% (days 1-2; P < .01) were significantly lower in the combination treatment group. Multivariate analysis showed that combination treatment was the only independent factor associated with lower 30-day mortality (OR, 0.06; 95% CI, 0.004-0.94; P = .04). CONCLUSIONS:Combination treatment reduced both 30- and 90-day mortality and length of hospital stay. Further study of the antiviral and immunomodulatory effects of this combination treatment of severe influenza is warranted. TRIAL REGISTRY:BioMed Central; No.: ISRCTN11273879 DOI 10.1186/ISRCTN11273879; URL: www.isrctn.com/ISRCTN11273879.

Background Pretreatment with topical imiquimod, a synthetic agonist of toll-like receptor 7, significantly improved the immunogenicity of influenza vaccination in elderly people. We aimed to clarify its effect in a younger age group.Methods In this double-blind, randomised controlled trial, we enrolled healthy volunteers aged 18-30 years in early 2014 to receive the 2013-14 northern-hemisphere winter trivalent influenza vaccine at the Queen Mary Hospital, (Hong Kong, China). Eligible participants were randomly assigned (1:1:1:1) to one of the four vaccination groups: the study group, topical imiquimod-cream followed by intradermal trivalent influenza vaccine (INF-Q-ID), or one of three control groups, topical aqueous-cream control followed by intradermal trivalent influenza vaccine (INF-C-ID), topical aqueous-cream control followed by intramuscular trivalent influenza vaccine (INF-C-IM), and topical imiquimod-cream followed by intradermal normal-saline injection (SAL-Q-ID) Randomisation was by computer generated lists in blocks of four. The type of topical treatment was masked from volunteers and investigators, although not from the study nurse. Serum haemagglutination-inhibition and microneutralisation-antibody titres were assayed. The primary outcome was seroconversion at day 7 after treatment for three vaccine strains of influenza (A/California/07/2009 H1N1-like virus [A/California/H1N1], A/Victoria/361/2011 H3N2-like virus [A/Victoria/H3N2], and B/Massachusetts/2/2012-like virus [B/Yamagata lineage]) and four non-vaccine strains (A/HK/485197/14 [H3N2 Switzerland-like lineage], prototype A/WSN/1933 [H1N1], A/HK/408027/09 [prepandemic seasonal H1N1], and B/HK/418078/11 [Victoria lineage]). Analysis was done on an intention-to-treat basis. This trial is registered with ClinicalTrials.gov, number NCT02103023.Findings We enrolled 160 healthy volunteers between March 1 and May 31,2014, and 40 participants were randomly assigned to each study group. For the A/California/H1N1 strain, seroconversion at day 7 occurred in 39 participants (98%) in the INF-Q-ID group, 25 (63%) in the INF-C-ID group, 18 (45%) in the INF-C-IM group, and none in the SAL-Q-ID group; for the A/Victoria/H3N2, this was 30 (75%) in the INF-Q-ID group, four (10%) in the INF-C-ID group, four (10%) in the INF-C-IM group, and none in the SAL-Q-ID group; and for the B/Massachusetts (Yamagata lineage) strain, this was 36 (90%) in the INF-Q-ID group, 27 (68%) in the INF-C-ID group, 17 (43%) in the INF-C-IM group, and one (3%) in the SAL-Q-ID group (p<0.0001 for all three vaccine strains). Adverse reactions were infrequent and self-limited and did not differ between the four groups. Furthermore, the seroconversion rate against the four non-vaccine strains was better in the INF-Q-ID group than in the control groups on days 7 and 21 (p<0.0001). The most common adverse events were grade 1 redness (five participants in the INF-Q-ID group, three in INF-C-ID, one in INF-C-IM, and one in SAL-Q-ID) and grade 1 swelling (seven participants in INF-Q-ID group, five in INF-C-ID, three in INF-C-IM, and two in SAL-Q-ID).Interpretation Topical application of imiquimod before intradermal trivalent influenza vaccine significantly improved immunogenicity against the vaccine influenza strains in young healthy individuals and increased immunogenicity against the non-vaccine strains, especially the antigenically drifted H3N2 strain of 2015, which was not included in the 2013-14 recommended vaccine. Further studies should be done to establish the efficacy and safety of this approach for other injectable vaccines to augment the onset and range of protection.

Background: The availability of HIV antiretroviral therapy (ART) has been associated with the development of transmitted drug resistance-associated mutations (TDRM). TDRM can compromise treatment effectiveness in patients initiating ART and the prevalence can vary in different clinical settings. In this study, we investigated the proportion of TDRM in treatment-naïve, recently infected HIV-positive individuals sampled from four urban locations across Asia between 2007–2010. Methods: Patients enrolled in the TREAT Asia Studies to Evaluate Resistance – Surveillance Study (TASER-S) were genotyped prior to ART initiation, with resulting resistance mutations analysed according to the WHO 2009 list. Results: Proportions of TDRM from recently infected individuals from TASER-S ranged from 0% to 8.7% Hong Kong: 3/88 (3.4%, 95% CI (0.71%-9.64%)); Thailand: Bangkok: 13/277 (4.7%, 95% CI (2.5%-7.9%)), Chiang Mai: 0/17 (0%, 97.5% CI (0%-19.5%)); and the Philippines: 6/69 (8.7%, 95% CI (3.3%-18.0%)). There was no significant increase in TDRM over time across all four clinical settings. Conclusions: The observed proportion of TDRM in TASER-S patients from Hong Kong, Thailand and the Philippines was low to moderate during the study period. Regular monitoring of TDRM should be encouraged, especially with the scale-up of ART at higher CD4 levels.

Changes in cerebral metabolite ratios (CMR) measured on 1H-MRS and changes in cognitive function (CF) are described in subjects commencing combination antiretroviral therapy (cART), although the dynamics of such changes are poorly understood.Neuroasymptomatic, HIV-infected subjects electively commencing cART were eligible. CMR were assessed in three anatomical voxels and CF assessed at baseline, week 48 and week 144. Overall differences in absolute change in CMRs and CF parameters between 0-48 and 48-144 weeks were assessed.Twenty-two subjects completed study procedures. Plasma HIV-RNA was <50 copies/mL in all at week 48 and in all, but two subjects at week 144. In general, between weeks 0-48 a rise in N-acetyl-aspartate(NAA)/Creatine(Cr) ratio and a decline in myo-Inositol(mI)/Cr ratio were observed. Between weeks 48-144, small rises in NAA/Cr ratio were observed in two anatomical voxels, whereas a rise in mI/Cr ratio was observed in all anatomical locations (0.31 (0.66) and -0.27 (1.35) between weeks 0-48 and 0.13 (0.91) and 1.13 (1.71) between weeks 48-144 for absolute changes in NAA/Cr and mI/Cr (SD) in frontal-grey voxel, respectively). Global CF score improved between weeks 0-48 and then declined between weeks 48-144 (0.63 (1.16) and -0.63 (0.1.41) for mean absolute change (SD) between weeks 0-48 and weeks 48-144, respectively).The direction of change of cerebral function parameters differs over time in HIV-infected subjects commencing cART, highlighting the need for long-term follow-up in such studies. The changes we have observed between weeks 48-144 may represent the initial development of cerebral toxicities from cART.

HIV drug resistance assessments and interpretations can be obtained from genotyping (GT), virtual phenotyping (VP) and laboratory‐based phenotyping (PT). We compared resistance calls obtained from GT and VP with those from PT (GT‐PT and VP‐PT) among CRF01_AE and subtype B HIV‐1 infected patients. GT predictions were obtained from the Stanford HIV database. VP and PT were obtained from Janssen Diagnostics BVBA's vircoTypeTM HIV‐1 and Antivirogram®, respectively. With PT assumed as the “gold standard,” the area under the curve (AUC) and the Bland–Altman plot were used to assess the level of agreement in resistance interpretations. A total of 80 CRF01_AE samples from Asia and 100 subtype B from Janssen Diagnostics BVBA's database were analysed. CRF01_AE showed discordances ranging from 3 to 27 samples for GT‐PT and 1 to 20 samples for VP‐PT. The GT‐PT and VP‐PT AUCs were 0.76–0.97 and 0.81–0.99, respectively. Subtype B showed 3–61 discordances for GT‐PT and 2–75 discordances for VP‐PT. The AUCs ranged from 0.55 to 0.95 for GT‐PT and 0.55 to 0.97 for VP‐PT. Didanosine had the highest proportion of discordances and/or AUC in all comparisons. The patient with the largest didanosine FC difference in each subtype harboured Q151M mutation. Overall, GT and VP predictions for CRF01_AE performed significantly better than subtype B for three NRTIs. Although discrepancies exist, GT and VP resistance interpretations in HIV‐1 CRF01_AE strains were highly robust in comparison with the gold‐standard PT. J. Med. Virol. 88:234–243, 2016. © 2015 Wiley Periodicals, Inc.

BACKGROUND:Imiquimod, a synthetic Toll-like receptor 7 agonist enhanced immunogenicity of influenza vaccine in a mouse model. We hypothesized that topical imiquimod before intradermal influenza vaccination (TIV) would produce similar effect in human.METHODS:We performed a prospective 1-year follow-up, double-blind, randomized, controlled trial with adults with comorbidities. Participants were randomized to 1 of the following 3 vaccinations: topical 5% 250 mg imiquimod ointment followed by intradermal TIV, topical aqueous-cream followed by intradermal TIV, or topical aqueous-cream followed by intramuscular TIV. Patients and investigators were blinded to the type of topical treatment applied. Hemagglutination inhibition (HI) and microneutralization antibody titers were measured. The primary outcome was the day 7 seroconversion rate.RESULTS:Ninety-one recruited participants completed the study. The median age was 73 years. On day 7, 27/30 (90%) patients who received imiquimod and intradermal TIV achieved seroconversion against the H1N1 strain by HI, compared with 4/30 (13.3%) who received aqueous-cream and intramuscular TIV (P < .001), and 12/31 (38.7%) who received aqueous-cream and intradermal TIV (P < .001). The seroconversion, seroprotection, and geometric mean titer-fold increase were met in all 3 strains in the imiquimod and intradermal TIV group 2 weeks earlier, and the better seroconversion rate was sustained from day 7 to year 1 (P ≤ .001). The better immunogenicity was associated with fewer hospitalizations for influenza or pneumonia (P < .05). All adverse reactions were self-limited.CONCLUSIONS:Pretreatment with topical imiquimod significantly expedited, augmented, and prolonged the immunogenicity of influenza vaccination. This strategy for influenza immunization should be considered for the elderly population.

To the Editors: The HIV epidemic among men who have sex with men (MSM) in Asia is expanding at an alarming rate, especially in several urban centers.1,2 Understanding the dynamics of HIV-1 transmission among MSM across large geographic areas may provide essential information on the origin of viral lineages and their epidemic expansion. Such estimates provide insights on the size and frequency of the disease spread, which can be used to facilitate the implementation of intervention strategies for prevention, such as the use of pre-exposure prophylaxis and combination antiretroviral therapy (cART).3,4 The availability of large data sets of genetic sequences from antiretroviral resistance surveillance activities and the use of phylodynamic tools allow for the identification and characterization of transmission clusters.5,6 In this study, we characterized the transmission clusters of HIV-1 among MSM across countries in East and Southeast Asia. A total of 1856 HIV-1 polymerase gene sequences from HIV-infected individuals were obtained from the TREAT Asia Studies to Evaluate Resistance—Monitoring (TASER-M) Database between 2006 and 2011. The details about this study have been described previously.7 Briefly, patients initiating first-line cART from participating urban hospitals in Hong Kong, Thailand, Malaysia, and the Philippines, were included. Ethics approvals were obtained from the local institutional review boards, and informed consent was obtained before baseline genotypic resistance testing. Polymerase genes were sequenced (HXB2 position: 2252-3263 nt) in laboratories participating in the TREAT Asia Quality Assurance Scheme (TAQAS)8 using in-house and/or commercially available resistance assays on specimens collected within 6 months before initiating cART. A total of 364 antiretroviral-naive MSM sequences were identified from the TASER-M database (Hong Kong, n = 118; Thailand, n = 124; Malaysia, n = 56; Philippines, n = 66). Following manual inspection (to remove problematic sequences) and phylogenetic inference, 144 subtype B and 186 CRF01_AE sequences from antiretroviral-naive MSM were identified and subjected to phylodynamic analysis. Unique recombinant forms and other rare subtypes (n = 29) were excluded from further analysis. Global MSM reference sequences of HIV-1 subtype B (n = 362) and CRF01_AE (n = 40) were retrieved from the HIV sequence database,9 in which sequences from other Asian countries (China, Mongolia, and Myanmar) were also included. Transmission clusters from the time-stamped sequence data sets were first deduced by neighbor-joining tree reconstruction followed by the more robust maximum likelihood and Bayesian maximum clade credibility inference implemented in PAUP version 4.0 (Sunderland, MA)10 and BEAST 1.7,11 respectively. Transmission cluster was defined based on the recently reported criteria: a phylogenetic cluster consisting of at least 2 isolates that form a clade supported by high bootstrap values (>90%) and Bayesian posterior probability value of 1 at the tree node.12–14 The divergence times or time of the most recent common ancestor (tMRCA) for each subtype B and CRF01_AE transmission clusters were estimated using the Bayesian coalescent methods as described previously.15 Phylogenetic reconstructions of the TASER-M data sets showed that a total of 68.1% of HIV-1 subtype B and 45.7% of CRF01_AE sequences were grouped in 50 transmission clusters of various sizes (mean size = 5.6, range = 2–32 sequences), with subtype B sequences having a higher tendency to form a cluster (P < 0.0001). Together with other Asian sequences from China, Mongolia, and Myanmar, a total of 34 clusters involving 154 subtype B-infected individuals and 16 clusters involving 125 subjects infected with CRF01_AE were estimated (Fig. 1A). In both subtypes, most clusters contained individuals from the same geographical origin (ie, country), although about 22.0% of the clusters comprised individuals from more than 1 country. This suggests that MSM networks in East and Southeast Asia were usually localized in their respective countries, with some clusters spanning beyond a single country. Genealogy-based analysis to estimate the tMRCA for each transmission network indicated the continued emergence of new subtype B and CRF01_AE clusters in the past 3 decades (Fig. 1B). The uninterrupted growth of each subepidemics of various cluster sizes suggests the role of transmission clusters as the continuous driving force of the epidemic among MSM in Asia.FIGURE 1: Transmission clusters and phylodynamic profile of HIV-1 subtype B and CRF01_AE among MSM in East and Southeast Asia. A, Distribution of HIV-1 subtype B and CRF01_AE transmission clusters across 7 countries in East and Southeast Asia. Size and frequency of transmission clusters were estimated based on the polymerase gene sequences (HXB2 position: 2252-3263 nt) from 506 and 226 MSM individuals infected with subtype B and CRF01_AE, respectively. In this study, transmission clusters are defined based on statistical supports generated at the internal nodes of the maximum likelihood and Bayesian maximum clade credibility tree reconstructions (bootstrap values of more than 90% and posterior probability of 1, respectively). B, Phylodynamic characteristics of HIV-1 subtype B and CRF01_AE transmission clusters. The Bayesian coalescent-based relaxed molecular clock analysis was performed as described elsewhere.15 The mean time of the most recent common ancestor (tMRCA), displayed in ascending order from the oldest to the youngest cluster, with the 95% highest posterior distribution for each transmission network is shown. The year in which cART was first introduced is also indicated.Information on HIV-1 transmission clusters generated by identifying genetically close virus variants circulating at a population level provides real-time direct evidence of an ongoing forward transmission that otherwise cannot be readily detected by conventional epidemiological surveillance. Despite expanded access to cART in some developing and developed nations in Asia, our analysis showed continued emergence of recent HIV-1 subtype B and CRF01_AE networks compared with the period in the 1980s and early 1990s where cART was less accessible. Although incomplete sampling or cluster extinction (dead-end transmission) may influence our interpretation16 and the fact that most of the TASER-M data sets were sampled primarily in 2008–2009 (62.4%), the observed trend suggests that increased access to cART in general may not be sufficient in reducing transmission clusters. The seemingly reduced transmission rates among individuals on cART could have been outpaced by the rapidly growing networks among undiagnosed and untreated MSM. Therefore, strategies such as early diagnosis and initiation of cART to reduce the risk of transmission among serodiscordant partners need to be urgently implemented and expanded across the region.3,4 The overall success of prevention or even harm reduction methods can in turn be assessed by monitoring the development of transmission networks, where in the presence of effective transmission control strategy, a significant decrease in the size and number of clusters over time should be observed. ACKNOWLEDGMENTS The authors thank the patients for their participations in this study.

Background: Because of the limitation of on-site neurology workforce, telestroke was implemented to overcome this barrier. We explored the efficacy and safety of intravenous (IV) stroke thrombolysis service by telestroke when neurologist was not available on-site. Methods: From January 2009 to December 2012, we compared patients treated with IV stroke thrombolysis by telestroke in the form of telephone consultation with teleradiology, to patients treated after in-person assessment by the same team of neurologists in a regional hospital. Door-to-needle time, symptomatic intracranial hemorrhage, and functional outcome at 3 months were prospectively collected and compared between the groups. Results: In all, 152 patients were treated with IV thrombolysis; 102 patients were treated with neurologist on-site; whereas 50 patients were treated by internists with telestroke. Fifty-two percent of the telemedical group achieved excellent outcome compared to 43% of the neurologist on-site group (P = .30). Symptomatic intracranial hemorrhage rate (4.0% versus 4.9%, P = 1.0) and mortality (8.3% versus 11.9%, P = .49) were comparable. Using the multiple logistic regression analysis, age, baseline stroke severity, and extent of early ischemic change on brain computed tomography scan, are independent predictors for excellent outcome, whereas the presence of neurologist on-site is not correlated with the outcome. Conclusions: Patients treated without neurologist on-site achieved similar outcome. Telephone consultation and teleradiology-guided IV stroke thrombolysis, with the support of on-site internist appeared safe and efficacious. (C) 2015 by National Stroke Association

Human immunodeficiency virus (HIV)-1 epidemics in Asian countries are driven by varying exposures. The epidemiology of the regional pandemic has been changing with the spread of HIV-1 to lower-risk populations through sexual transmission. Common HIV-1 genotypes include subtype B and circulating recombinant form (CRF) 01_AE. Our objective was to use HIV-1 genotypic data to better quantify local epidemics. TASER-M is a multicenter prospective cohort of HIV-infected patients. Associations between HIV exposure, patient sex, country of sample origin and HIV-1 genotype were evaluated by multivariate logistic regression. Phylogenetic methods were used on genotypic data to investigate transmission relationships. A total of 1086 patients from Thailand, Hong Kong, Malaysia and the Philippines were included in analyses. Proportions of male patients within countries varied (Thailand: 55.6%, Hong Kong: 86.1%, Malaysia: 81.4%, Philippines: 93.8%; p < 0.001) as did HIV exposures (heterosexual contact: Thailand: 85.7%, Hong Kong, 46.2%, Malaysia: 47.8%, Philippines: 25.0%; p < 0.001). After adjustment, we found increased subtype B infection among men who have sex with men, relative to heterosexual-reported exposures (odds ratio = 2.4, p < 0.001). We further describe four transmission clusters of eight to 15 treatment naïve, predominantly symptomatic patients (two each for subtype B and CRF01_AE). Risk-group subpopulations differed with respect to the infecting HIV-1 genotype. Homosexual exposure patients had higher odds of being infected with subtype B. Where HIV-1 genotypes circulate within countries or patient risk-groups, local monitoring of genotype-specific transmissions may play a role in focusing public health prevention strategies. Phylogenetic evaluations provide complementary information for surveillance and monitoring of viruses with high mutation rates such as HIV-1 and Ebola.

Background: HIV-associated neurocognitive disorder incurs a significant burden on HIV patients in Asia-Pacific countries; however, the incidence is difficult to estimate due to a lack of local epidemiological data. The impact of neurocognitive impairment in HIV patients is often underestimated due to a lack of education and awareness, and there are consequently gaps in the provision of screening and diagnosis to enable earlier intervention to limit neurocognitive impairment.Method: This review seeks to redress the imbalance by promoting awareness and education among physicians concerning the neurovirulence of HIV and thereby increase screening efforts to improve diagnosis rates and clinical outcomes for underserved patients in this region. The Asia, Australia, and Middle East (AAME) HAND Advisory Board convened expert regional representatives to review current practice and recommend appropriate measures related to the implementation of standardised screening programmes and treatment recommendations to curb the developing HAND epidemic in the region. In particular, we recommend basic neuropsychological testing protocols that could be efficiently introduced into clinical practice for routine screening.Result: We also propose simple guidelines for the management of HAND. We believe that HAND is a significant and under-reported diagnosis in HIV patients that warrants both greater recognition and further clinical investigation of the underlying pathophysiology and the impact of HIV disease progression, with HAND being associated with worse medication adherence and therefore possibly increased risk of ARV treatment failure.Discussion: Widespread screening will lead to greater recognition of HAND and earlier intervention, which may lead to improved management strategies in the future. (C) 2015 Elsevier B.V. All rights reserved.

Background The World Health Organization recommends HBV–HIV-coinfected individuals start antiretroviral therapy containing tenofovir. Here we describe first-line tenofovir use and treatment outcomes in coinfected patients in Asia. Methods HBV surface antigen positive patients enrolled in the TREAT Asia HIV Observational Database who started first-line antiretroviral therapy were included. Logistic regression adjusted for period of treatment initiation was used to determine factors associated with tenofovir use. Generalized estimating equations were used to evaluate factors associated with alanine transaminase levels and CD4+ T-cell count on treatment. Results There were 548 eligible patients, of whom 149 (27.2%) started tenofovir. Patients treated in high/high-middle income countries (odds ratio 4.4 versus low/low-middle, 95% CI 2.6, 7.4; P<0.001) and those with elevated baseline alanine transaminase (odds ratio 4.2 versus normal, 95% CI 2.4, 7.2; P<0.001) were more likely to receive tenofovir. Hepatitis C antibody positive patients (odds ratio 0.4 versus negative, 95% CI 0.2, 0.8; P=0.008) were less likely. In those starting antiretroviral therapy with elevated alanine transaminase, mean reduction after tenofovir initiation was 11.2 IU/l (95% CI 0.9, 21.6; P=0.034) lower compared with those using a non-tenofovir-based regimen although this did not significantly increase the chance of alanine transaminase normalization. Tenofovir use was not associated with a superior CD4+ T-cell response. Conclusions HBV–HIV-coinfected patients in Asia are most likely to receive tenofovir if they are treated in a high/high-middle income country, have elevated alanine transaminase levels and are hepatitis C antibody negative. Compared to other antiretroviral therapies, tenofovir-based regimens more effectively reduce liver inflammation in HBV–HIV-coinfection but do not result in superior CD4+ T-cell recovery.