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2.  Identification of New CRF51_01B in Singapore Using Full Genome Analysis of Three HIV Type 1 Isolates 
A recent HIV-1 molecular epidemiology survey in Singapore identified a novel CRF01_AE/B recombinant form, which accounted for 13 (11.9%) of 109 patient samples. Peripheral blood mononuclear cell DNA from three of these 13 patients was used to generate near full-length sequences to characterize the novel CRF01_AE/B recombinant form. The three isolates had a recombinant structure composed of CRF01_AE and subtype B, and shared identical breakpoints. As the three patients were not epidemiologically linked, this recombinant form has been designated CRF51_01B. Identification of the novel recombinant forms indicates ongoing active HIV-1 transmission in Singapore.
PMCID: PMC3332370  PMID: 21902588
3.  High prevalence of CXCR4 usage among treatment-naive CRF01_AE and CRF51_01B-infected HIV-1 subjects in Singapore 
Recent studies suggest HIV-1 inter-subtype differences in co-receptor usage. We examined the correlation between HIV-1 subtype and co-receptor usage among treatment-naïve HIV-1 subjects in Singapore. Additionally, we investigated whether the subtype co-receptor association was influenced by stage of infection.
V3 sequences of HIV-1 envelope protein gp120 were obtained from 110 HIV treatment-naïve patients and genotypic co-receptor tropism determination was performed using Geno2pheno. Two false-positive rate (FPR) cut-offs, 10% and 5.75% were selected for tropism testing.
Subtype assignment of viral strains from 110 HIV-infected individuals based on partial sequencing of HIV-1 pol, gp120 and gp41 were as follows: 27 subtype B, 64 CRF01_AE, 10 CRF51_01B, and 9 other subtypes. At FPR=10%, 10 (100%) CRF51_01B-infected subjects and 26 (40.6%) CRF01_AE-infected subjects had CXCR4-using virus, compared to 7 (25.9%) subtype B subjects and 1 (11.1%) CRF33_01B-infected subject (P < 0.001). At FPR=5.75%, 10 (100%) CRF51_01B-infected subjects and 20 (31.3%) CRF01_AE-infected subjects had CXCR4-using virus, compared to 4 (14.8%) subtype B and 1 (11.1%) CRF33_01B-infected subjects (P < 0.001). Among those with evidence of seroconversion within 2 years prior to study enrolment, 100% of CRF51_01B-infected subjects had CXCR4-using virus, independent of Geno2pheno FPR.
CRF51_01B and CRF01_AE-infected individuals have higher prevalence of CXCR4-usage compared to subtype B infected individuals. Further studies examining these differences could help optimise the use of CCR5-antagonist in populations with these subtypes, and increase our understanding of HIV-1 biology.
PMCID: PMC3585921  PMID: 23421710
CXCR4 usage; HIV-1; treatment-naïve
4.  Molecular Epidemiology of HIV Type 1 in Singapore and Identification of Novel CRF01_AE/B Recombinant Forms 
AIDS Research and Human Retroviruses  2011;27(10):1135-1137.
To investigate HIV-1 molecular epidemiology in Singapore, we sequenced portions of three regions of the HIV-1 genome (protease HXB2: 2163 to 2620, gp120 HXB2: 6904 to 7628, and gp41 HXB2: 7817 to 8264) from 212 plasma samples collected between February 2008 and August 2009. From these samples, 109 (51.4%) generated interpretable data in all regions. Sixty-one (56.0%) were identified as CRF01_AE, 26 (23.9%) as subtype B and 14 (12.8%) as possible novel recombinant forms. The main novel recombinant pattern, detected in 13 sequences, had subtype B in protease and gp41 and CRF01_AE in gp120. There was intermixing of subtypes within transmission risk groups. However, 85% of subjects infected with the novel recombinant forms self-identified as men who have sex with men or bisexuals compared with only 41% of individuals infected with CRF01_AE and 62% infected with subtype B (p = 0.001).
PMCID: PMC3186691  PMID: 21235306
5.  Accuracy and User-Acceptability of HIV Self-Testing Using an Oral Fluid-Based HIV Rapid Test 
PLoS ONE  2012;7(9):e45168.
The United States FDA approved an over-the-counter HIV self-test, to facilitate increased HIV testing and earlier linkage to care. We assessed the accuracy of self-testing by untrained participants compared to healthcare worker (HCW) testing, participants’ ability to interpret sample results and user-acceptability of self-tests in Singapore.
Methodology/Principal Findings
A cross-sectional study, involving 200 known HIV-positive patients and 794 unknown HIV status at-risk participants was conducted. Participants (all without prior self-test experience) performed self-testing guided solely by visual instructions, followed by HCW testing, both using the OraQuick ADVANCE Rapid HIV 1/2 Antibody Test, with both results interpreted by the HCW. To assess ability to interpret results, participants were provided 3 sample results (positive, negative, and invalid) to interpret. Of 192 participants who tested positive on HCW testing, self-testing was positive in 186 (96.9%), negative in 5 (2.6%), and invalid in 1 (0.5%). Of 794 participants who tested negative on HCW testing, self-testing was negative in 791 (99.6%), positive in 1 (0.1%), and invalid in 2 (0.3%). Excluding invalid tests, self-testing had sensitivity of 97.4% (95% CI 95.1% to 99.7%) and specificity of 99.9% (95% CI: 99.6% to 100%). When interpreting results, 96%, 93.1% and 95.2% correctly read the positive, negative and invalid respectively. There were no significant demographic predictors for false negative self-testing or wrongly interpreting positive or invalid sample results as negative. Eighty-seven percent would purchase the kit over-the-counter; 89% preferred to take HIV tests in private. 72.5% and 74.9% felt the need for pre- and post-test counseling respectively. Only 28% would pay at least USD15 for the test.
Self-testing was associated with high specificity, and a small but significant number of false negatives. Incorrectly identifying model results as invalid was a major reason for incorrect result interpretation. Survey responses were supportive of making self-testing available.
PMCID: PMC3444491  PMID: 23028822
6.  Renal safety of tenofovir containing antiretroviral regimen in a Singapore cohort 
Tenofovirdisoproxilfumarate (TDF) is a nucleotide analogue widely recommended in international HIV treatment guidelines. The association of TDF and renal dysfunction has remained an area of interest.
We conducted a retrospective review of all patients on TDF from July 2007 to December 2009 in our institution and evaluated their renal function. Absolute change of creatinine clearance (CLCr) using Cockroft-Gault equation from baseline was calculated at 6, 12, 18 and 24 months. Overall, 226 patients were included in the study. Ninety percent were male. The median age was 46 yrs old (23–82), median weight was 60 kg (IQR 53.75-68), median CD4 count was 127 cells/mm3 (IQR 38–258) and median CLCr 82.7 mL/min (IQR 71.4-101.7) on initiation of TDF. The median decline of CLCr from baseline was −3.9 ml/min (IQR −12.3 to 7.6), and −3.6 ml/min (IQR −12.4 to 6.7) at 12 (n = 102), 24 months (n = 75) respectively. Eighteen of 226 patients had a decline in renal function to
While we noted renal toxicity to be rare and transient among our cohort receiving TDF as part of their ARV regimen, these results reflect the short term renal effects of TDF given that ARV treatment is lifelong. Given that laboratory monitoring may be difficult to implement in many situations, future prospective studies looking into an evidence based algorithm for less frequent renal function monitoring than current guideline recommendations may be helpful.
PMCID: PMC3443451  PMID: 22703627
Tenofovir; Kidney; Antiretrovirals
PLoS ONE  2012;7(4):e34663.
Since 2008, the Singapore Ministry of Health (MOH) has expanded HIV testing by increasing anonymous HIV test sites, as well as issuing a directive to hospitals to offer routine voluntary opt out inpatient HIV testing. We reviewed this program implemented at the end of 2008 at Tan Tock Seng Hospital (TTSH), the second largest acute care general hospital in Singapore.
Methods and Findings
From January 2009 to December 2010, all inpatients aged greater or equal than 21 years were screened for HIV unless they declined or were not eligible for screening. We reviewed the implementation of the Opt Out testing policy. There were a total of 93,211 admissions; 41,543 patients were included based on HIV screening program eligibility criteria. Among those included, 79% (n = 32,675) opted out of HIV screening. The overall acceptance rate was 21%. Majority of eligible patients who were tested (63%) were men. The mean age of tested patients was 52 years. The opt out rate was significantly higher among females (OR: 1.5, 95%CI: 1.4–1.6), aged >60 years (OR: 2.3, 95%CI: 2.2–2.4) and Chinese ethnicity (OR: 1.7, 95%CI:1.6–1.8). The false positive rate of the HIV screening test is 0.56%. The proportion of patients with HIV infection among those who underwent HIV screening is 0.18%. All16 confirmed HIV patients were linked to care.
The default opt-in rate of inpatient HIV testing was low at Tan Tock Seng Hospital, Singapore. Efforts to address individual HIV risk perception and campaigns against HIV stigma are needed to encourage more individuals to be tested for HIV.
PMCID: PMC3321033  PMID: 22493708
BMJ Open  2012;2(1):e000662.
To estimate the prevalence of HIV-associated neurocognitive disorders (HAND) among HIV patients in a multiethnic South Asian population, describe the pattern of neurocognitive impairment in HAND and the factors associated with HAND.
A cross-sectional survey of HIV-positive outpatients and inpatients.
The sole referral centre for HIV/AIDS treatment in Singapore.
Inclusion criteria were HIV positive, age between 21 and 80 years old and at least 3 years of education. Exclusion criteria included concomitant delirium, serious systemic disease or major psychiatric illness. 265 patients did not meet criteria or declined to participate. The final sample size was 132.
Outcome measures
The primary outcome measure was cognitive impairment based on performance on the Montreal Cognitive Assessment, International HIV Dementia Scale and Instrumental Activities of Daily Living. The secondary outcome measure was the classification of impairment based on the 2007 updated research nosology for HAND.
The prevalence of HAND was 22.7% of which 70% (15.9% of total) were asymptomatic neurocognitive impairment, 23.3% (5.3% of total) were mild neurocognitive disorder and 6.7% (1.5% of total) were HIV-associated dementia. Increasing age (OR 1.104, 95% CI 1.054 to 1.155, p<0.001), less education (OR 0.78, 95% CI 0.69 to 0.89, p<0.001) and low baseline CD4 count (OR 0.15, 95% CI 0.03 to 0.74, p=0.019) were associated with HAND. Delayed recall, language and abstract thinking were the domains most commonly affected, but impairment in visuospatial ability (RC 3.013, 95% CI 1.954 to 4.073, p<0.001) and attention (RC 2.205, 95% CI 1.043 to 3.367, p<0.001) were most strongly associated with HAND.
HAND is common among HIV patients in a South Asian sample, most of whom are asymptomatic. Older patients with less education and severe illness at diagnosis are at highest risk of HAND. Delayed recall is most commonly affected, but visuospatial dysfunction is most strongly associated with prevalent HAND.
Article summary
Article focus
What is the prevalence of HIV-associated neurocognitive disorders (HAND) in South Asia?
What are the demographic and clinical characteristics of South Asian individuals with HAND?
Key messages
The estimated prevalence of HAND in South Asia is high.
Older patients with less education and more severe HIV illness at diagnosis are at highest risk for HAND.
Early diagnosis of HIV and access to care and treatment is essential.
Strengths and limitations of this study
The article's strengths are it is the first study on HAND in a representative multiethnic South Asian population and it used a method of detection that is applicable to local clinical practice.
The limitations are the small sample size and non-comparability with other HAND studies due to different methods used in detection of HAND cases.
Another major limitation is the lack of published local normative data on the tools used.
PMCID: PMC3282293  PMID: 22331389
Emerging Infectious Diseases  2010;16(1):21-26.
During the containment phase, regions of exposure for imported infections changed rapidly.
In June 2009, during Singapore’s pandemic influenza plan containment phase, pandemic (H1N1) 2009 was introduced into the country through imported cases. To understand how travel patterns affected the initial outbreak, we examined epidemiologic and travel data for the first 116 case-patients admitted to Tan Tock Seng Hospital, Singapore, with travel-associated infection. Sixty-one percent and 54% of patients, respectively, met US Centers for Disease Control and Prevention and World Health Organization temperature criteria for influenza-like illness. One fourth of the case-patients traveled after illness onset, and 15% became ill while traveling. Regions of exposure for imported infections changed rapidly; case-patients initially arrived from North America, followed by Australasia and Southeast Asia. Case-patients on longer flights were more likely to become ill before arrival; those with shorter flights tended to become ill after arrival. Thermal scanners detected fevers in 12% of the arriving case-patients, resulting in a shorter time to isolation.
PMCID: PMC2874386  PMID: 20031038
Influenza A virus; pandemic (H1N1) 2009; travel; influenza; pandemic; disease transmission; viruses; Singapore; expedited; research
PLoS Medicine  2007;4(6):204.
The authors discuss the challenges of providing HIV treatment to a marginalized population: prisoners in Thailand.
PMCID: PMC1896202  PMID: 17593894

Results 1-11 (11)