Displaying all 12 publications

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  1. Yee LN, Chuah JA, Chong ML, Phang LY, Raha AR, Sudesh K, et al.
    Microbiol Res, 2012 Oct 12;167(9):550-7.
    PMID: 22281521 DOI: 10.1016/j.micres.2011.12.006
    In this study, PHA biosynthesis operon of Comamonas sp. EB172, an acid-tolerant strain, consisting of three genes encoding acetyl-CoA acetyltransferase (phaA(Co) gene, 1182 bp), acetoacetyl-CoA reductase (phaB(Co) gene, 738 bp) and PHA synthase, class I (phaC(Co) gene, 1694 bp) were identified. Sequence analysis of the phaA(Co), phaB(Co) and phaC(Co) genes revealed that they shared more than 85%, 89% and 69% identity, respectively, with orthologues from Delftia acidovorans SPH-1 and Acidovorax ebreus TPSY. The PHA biosynthesis genes (phaC(Co) and phaAB(Co)) were successfully cloned in a heterologous host, Escherichia coli JM109. E. coli JM109 transformants harbouring pGEM'-phaC(Co)AB(Re) and pGEM'-phaC(Re)AB(Co) were shown to be functionally active synthesising 33 wt.% and 17 wt.% of poly(3-hydroxybutyrate) [P(3HB)]. E. coli JM109 transformant harbouring the three genes from the acid-tolerant Comamonas sp. EB172 (phaCAB(Co)) under the control of native promoter from Cupriavidus necator, in vivo polymerised P(3HB) when fed with glucose and volatile mixed organic acids (acetic acid:propionic acid:n-butyric acid) in ration of 3:1:1, respectively. The E. coli JM109 transformant harbouring phaCAB(Co) could accumulate P(3HB) at 2g/L of propionic acid. P(3HB) contents of 40.9% and 43.6% were achieved by using 1% of glucose and mixed organic acids, respectively.
  2. Chong SCS, Kamarulzaman A, Azwa I, Ng RX, Chong ML, Raman N, et al.
    Sex Health, 2021 05;18(2):147-155.
    PMID: 33715762 DOI: 10.1071/SH20180
    Background By the end of 2017, an estimated 83% of people living with HIV in Malaysia knew their serostatus. However, the Ministry of Health reported a high proportion of those newly diagnosed had low CD4 counts <200 cells/µL, indicating late presentation for testing may be pervasive.

    METHODS: A qualitative study was conducted to explore the context and experiences of people at risk of HIV infection testing and seeking treatment later in the course of their infection. Participants recruited (n = 20) were HIV positive, aged >18 years who fit the description of late presentation (World Health Organization defined as CD4 cell count <350 cells/µL). Semi-structured interviews were conducted, and a framework approach was used to interrogate the data.

    RESULTS: Many participants perceived themselves at low risk of HIV infection and did not undergo routine voluntary testing; rather, they were diagnosed when seeking treatment for serious illness or as part of mandatory employment-related testing. Perceived lack of confidentiality and potential discriminatory behaviour at public health facilities were significant deterrents to testing. Participants were satisfied with HIV treatment, but rarely sought psychosocial support in order to 'protect' their privacy.

    CONCLUSION: Unless drivers of HIV infection are effectively addressed, including stigmatising and discriminatory practices, and low health literacy, the occurrence of late presentation will persist. Their collective impact will not only jeopardise efforts to improve the treatment cascade, but may also impact engagement with other biomedical prevention and care technologies.

  3. Leng CY, Low HC, Chua LL, Chong ML, Sulaiman H, Azwa I, et al.
    HIV Med, 2017 05;18(5):321-331.
    PMID: 27649852 DOI: 10.1111/hiv.12432
    OBJECTIVES: Human papillomavirus (HPV)-associated cancers disproportionately affect those infected with HIV despite effective combination antiretroviral therapy (cART). The primary aim of this study was to quantify HPV16 and HPV52 E6-specific interferon (IFN)-γ enzyme-linked immunospot (ELISPOT) T-cell responses, a correlate of protective immunity, in the first year following cART initiation and subsequently in those patients with suboptimal (sIR) and optimal (oIR) immune reconstitution.

    METHODS: Ninety-four HIV-infected patients were recruited to the study; a longitudinal cohort of patients recruited just prior to commencing cART and followed up for 48 weeks (n = 27), and a cross-sectional cohort (n = 67) consisting of patients with sIR (CD4 T-cell count < 350 cells/μL) and oIR (CD4 T-cell count > 500 cells/μL) after a minimum of 2 years on cART. Controls (n = 29) consisted of HIV-negative individuals. IFN-γ ELISPOT responses against HPV16 and HPV52 E6 were correlated to clinical characteristics, anal and oral HPV carriage, T-cell maturational subsets, markers of activation, senescence and T-regulatory cells.

    RESULTS: HPV16 and HPV52 E6-specific T-cell responses were detected in only one of 27 patients (3.7%) during the initial phase of immune recovery. After at least 2 years of cART, those who achieved oIR had significantly higher E6-specific responses (9 of 34; 26.5%) compared with those with sIR (2 of 32; 6.3%) (P = 0.029). Apart from higher CD4 T-cell counts and lower CD4 T-cell activation, no other immunological correlates were associated with the detection of HPV16 and HPV52 E6-specific responses.

    CONCLUSIONS: HPV16 and HPV52 E6-specific IFN-γ T-cell responses, a correlate of protective immunity, were detected more frequently among HIV-infected patients who achieved optimal immune recovery on cART (26.5%) compared with those with suboptimal recovery (6.3%).

  4. Mukherjee T, Sakthivel R, Fong HY, McStea M, Chong ML, Omar SF, et al.
    AIDS Behav, 2018 Oct;22(10):3226-3233.
    PMID: 29508103 DOI: 10.1007/s10461-018-2073-x
    This study determines the optimal cut-off scores for the Montreal Cognitive Assessment (MoCA) to detect HIV-associated neurocognitive disorders (HAND) in a multi-ethnic Malaysian HIV-positive cohort by developing demographically corrected normative standards among 283 HIV-negative community-based controls with overlapping demographic characteristics. The norms (corrected for age, sex, education, ethnicity) were applied to 342 HIV-positive virally suppressed individuals on cART. Impairment rates were classified using the Global Deficit Score (GDS ≥ .5) method. The MoCA was also scored according to the recommended cut-off of ≤ 26, and functional decline was applied to both impairment definitions to classify HAND per the Frascati criteria. The ≤ 26 cut-off considerably overestimated cognitive impairment in both samples (59.4% HIV-negative; 69.3% HIV-positive). In contrast, corrected scores yielded impairment rates consistent with what has been reported internationally in virally suppressed cohorts (23.4% with 83.3% mild impairment, 16.7% moderate impairment). A supplemental file allowing the computation of corrected MoCA scores and impairment status is included.
  5. Kared H, Martelli S, Tan SW, Simoni Y, Chong ML, Yap SH, et al.
    Front Immunol, 2018;9:686.
    PMID: 29731749 DOI: 10.3389/fimmu.2018.00686
    Repetitive stimulation by persistent pathogens such as human cytomegalovirus (HCMV) or human immunodeficiency virus (HIV) induces the differentiation of natural killer (NK) cells. This maturation pathway is characterized by the acquisition of phenotypic markers, CD2, CD57, and NKG2C, and effector functions-a process regulated by Tim-3 and orchestrated by a complex network of transcriptional factors, involving T-bet, Eomes, Zeb2, promyelocytic leukemia zinc finger protein, and Foxo3. Here, we show that persistent immune activation during chronic viral co-infections (HCMV, hepatitis C virus, and HIV) interferes with the functional phenotype of NK cells by modulating the Tim-3 pathway; a decrease in Tim-3 expression combined with the acquisition of inhibitory receptors skewed NK cells toward an exhausted and cytotoxic phenotype in an inflammatory environment during chronic HIV infection. A better understanding of the mechanisms underlying NK cell differentiation could aid the identification of new immunological targets for checkpoint blockade therapies in a manner that is relevant to chronic infection and cancer.
  6. Abdul Aziz SA, Mcstea M, Ahmad Bashah NS, Chong ML, Ponnampalavanar S, Syed Omar SF, et al.
    AIDS, 2018 05 15;32(8):1025-1034.
    PMID: 29547442 DOI: 10.1097/QAD.0000000000001798
    OBJECTIVES: In a clinic-based, treated HIV-infected cohort, we identified individuals with sarcopenia and compared with age, sex and ethnically matched controls; and investigated associated risk factors and health outcomes.

    DESIGN: Sarcopenia (age-related muscle loss) causes significant morbidity to the elderly, leading to frequent hospitalizations, disability and death. Few have characterized sarcopenia in the HIV-infected who experience accelerated aging.

    METHODS: Sarcopenia was defined as low muscle mass with weak grip strength and/or slow gait speed using lower 20th percentiles of controls. Multivariate logistic and linear regression analyses were used to explore risk factors and health-related outcomes associated with sarcopenia among HIV-infected individuals.

    RESULTS: We recruited 315 HIV-infected individuals aged at least 25 years with at least 1-year history of undetectable viral load on treatment (HIV RNA <50 copies/ml). Percentage of sarcopenia in 315 HIV-infected was 8%. Subsequently, 153 of the 315 were paired with age, sex and ethnically matched HIV-uninfected. The percentage of sarcopenia in the HIV-infected (n = 153) compared with uninfected (n = 153) were 10 vs. 6% (P = 0.193) respectively, whereas of those at least 50 years of age among them were 17% vs. 4% (P = 0.049), respectively. Associated risk factors among the HIV-infected include education level, employment status, BMI, baseline CD4 cell count, duration on NRTIs and GGT levels. Identified negative outcomes include mortality risk scores [5.42; 95% CI 1.46-9.37; P = 0.007) and functional disability (3.95; 95% CI 1.57-9.97; P = 0.004).

    CONCLUSION: Sarcopenia is more prevalent in HIV-infected at least 50 years old compared with matched controls. Our findings highlight associations between sarcopenia with loss of independence and greater healthcare burden among treated HIV-infected individuals necessitating early recognition and intervention.

  7. Wong HY, Wong PL, Bador MK, Chong ML, Shenoi S, Rozanova J, et al.
    J Acquir Immune Defic Syndr, 2023 May 01;93(1):64-72.
    PMID: 36716735 DOI: 10.1097/QAI.0000000000003169
    BACKGROUND: In resource-limited settings, HIV-related services are often targeted to younger key populations, although increasing reports have found that adults ≥50 years now account for among the highest increase in new HIV diagnosis. We assessed the proportion of new HIV infections among older adults (≥50 years) and compared their sociodemographics, risk behaviors, and HIV-related outcomes to newly diagnosed younger adults (<50 years).

    METHODS: This retrospective analysis included all new HIV diagnosis from 2016 to 2019 at the University of Malaya Medical Centre, Malaysia. Trends of HIV diagnosis was assessed using join point regression analysis, and characteristics between the older and younger adults were compared using χ 2 test or Mann-Whitney U test. Kaplan-Meier analysis and log-rank test were used to compare the survival probability in both age groups.

    RESULTS: From a total of 594 new HIV diagnosis between 2016 and 2019, 11.5% (N = 68) were among older adults with an annual percent increase of 5.50%. Older adults were more likely ethnic Indians ( P < 0.001), acquired HIV through heterosexual contact ( P = 0.001), had late presentation to care ( P = 0.003), and multimorbidity ( P < 0.001). Immunological responses after 12 months on antiretroviral therapy were comparable in both the groups. Older adults had a higher probability of death compared with younger adults (adjusted hazard ratio 1.81, 95% confidence interval: 1.02 to 3.23, P = 0.043) after adjusting for sex, mode of HIV transmission, late presentation to care, antiretroviral therapy initiation, and multimorbidity.

    CONCLUSION: Older adults diagnosed with HIV were associated with late care presentation and increased mortality. There is an urgent need to enhance uptake of HIV testing and linkage to care among older individuals in our setting.

  8. Neelamegam M, Ahmad A, Chong ML, Wong PL, Zulhaimi NS, Cysique L, et al.
    AIDS Care, 2023 Sep 04.
    PMID: 37666210 DOI: 10.1080/09540121.2023.2254543
    HIV-associated mortality has improved with the advent of antiretroviral therapy, yet neurocognitive decline persists. We assessed the association between psychosocial risk factors and cognitive function among Malaysian PLWH. Data of virally suppressed PLWH (n = 331) on stable ART, from the Malaysian HIV and Aging study was assessed. Psychosocial factors were assessed using the Lubben Social Network Scale-6 (social isolation) and Depression Anxiety Stress Scale-21 (DASS-21). The Montreal Cognitive Assessment (MoCA) with normative standards for the Malaysian population was used to determine cognitive function. Linear and logistic regression were used to assess the associations between cognition, and psychosocial risk factors. Median age of participants was 43.8 years (IQR 37.7-51.0). Participants were predominantly male (82.8%), with secondary education or higher (85.2%). Participants were on ART for 5.7 years (IQR 3.0-9.7), with a mean MoCA score of 24.6 (±3.7). Social isolation was found in 34.6% of participants, and severe depression, severe stress, and severe anxiety in 10.6%, 15.4%, and 6.0% respectively. After adjusting for demographic, clinical, and HIV parameters, MoCA scores were significantly associated with severe stress (β = -0.11, p = 0.02) and having marginal friendship ties (β = -0.13, p = 0.03). Social isolation and severe stress are associated with neurocognitive impairment in PLWH.
  9. Yap SH, Abdullah NK, McStea M, Takayama K, Chong ML, Crisci E, et al.
    PLoS One, 2017;12(10):e0186000.
    PMID: 29016635 DOI: 10.1371/journal.pone.0186000
    BACKGROUND: Co-infections with human herpesvirus (HHV) have been associated with residual chronic inflammation in antiretroviral (ART)-treated human immunodeficiency virus (HIV)-infected individuals. However, the role of HHV in modulating the tryptophan-kynurenine pathway and clinical outcomes in HIV-infected individuals is poorly understood. Thus, we investigated the seroprevalence of four common HHVs among treated HIV-infected participants and their impact on kynurenine/tryptophan (K/T) ratio and long-term CD4 T-cell recovery in HIV/HHV co-infected participants.

    METHOD: In this cross-sectional study, HIV-infected participants receiving suppressive ART for a minimum of 12 months were recruited from the University Malaya Medical Centre (UMMC), Malaysia. Stored plasma was analyzed for CMV, VZV, HSV-1 and HSV-2 IgG antibody levels, immune activation markers (interleukin-6, interferon-γ, neopterin and sCD14), kynurenine and tryptophan concentrations. The influence of the number of HHV co-infection and K/T ratio on CD4 T-cell recovery was assessed using multivariate Poisson regression.

    RESULTS: A total of 232 HIV-infected participants were recruited and all participants were seropositive for at least one HHV; 96.1% with CMV, 86.6% with VZV, 70.7% with HSV-1 and 53.9% with HSV-2. K/T ratio had a significant positive correlation with CMV (rho = 0.205, p = 0.002), VZV (rho = 0.173, p = 0.009) and a tendency with HSV-2 (rho = 0.120, p = 0.070), with CMV antibody titer demonstrating the strongest modulating effect on K/T ratio among the four HHVs assessed in SOM analysis. In multivariate analysis, higher K/T ratio (p = 0.03) and increasing number of HHV co-infections (p<0.001) were independently associated with poorer CD4 T-cell recovery following 12 months of ART initiation.

    CONCLUSION: Multiple HHV co-infections are common among ART-treated HIV-infected participants in the developing country setting and associated with persistent immune activation and poorer CD4 T-cell recovery.

  10. Rajasuriar R, Chong ML, Ahmad Bashah NS, Abdul Aziz SA, Mcstea M, Lee ECY, et al.
    AIDS, 2017 06 19;31(10):1393-1403.
    PMID: 28358731 DOI: 10.1097/QAD.0000000000001475
    BACKGROUND: Aging among HIV-infected individuals on antiretroviral therapy (ART) is a significant clinical challenge; however, studies assessing multidimensional aspects of aging are lacking. We characterized 10 geriatric conditions encompassing multiple functional domains, its health impact and associated risk factors in HIV-infected and age-matched uninfected controls.

    METHODS: HIV-infected individuals were recruited from the outpatient clinic in University Malaya Medical Centre, Malaysia and controls from the community. All participants were aged at least 25 years of age with no acute illness, and HIV-infected individuals were on stable ART. Geriatric conditions were assessed and the burden scored as a composite of geriatric conditions present in an individual (total score = 10). Multivariate regression analysis was performed to determine the risk factors and health impact associated with the burden of geriatric conditions.

    RESULTS: We analyzed data from 336 HIV-infected individuals (total HIV+), of whom 172 were matched for age, sex, and ethnicity with 172 HIV-uninfected controls (matched subset). In the total HIV-positive cohort, median (interquartile range) age was 44 (38-51) years and CD4 T-cell count was 562 (398-737) cells/μl. The burden of geriatric conditions was significantly higher in the HIV-infected group compared with controls (P 
  11. Ross JL, Jiamsakul A, Avihingsanon A, Lee MP, Ditangco R, Choi JY, et al.
    AIDS Behav, 2022 Dec;26(12):3862-3877.
    PMID: 35668223 DOI: 10.1007/s10461-022-03714-5
    Despite the mental health and substance use burden among people living with HIV (PLHIV) in the Asia-Pacific, data on their associations with HIV clinical outcomes are limited. This cross-sectional study of PLHIV at five sites assessed depression and substance use using PHQ-9 and ASSIST. Among 864 participants, 88% were male, median age was 39 years, 97% were on ART, 67% had an HIV viral load available and mL, 19% had moderate-to-severe depressive symptoms, and 80% had ever used at least one substance. Younger age, lower income, and suboptimal ART adherence were associated with moderate-to-severe depressive symptoms. Moderate-to-high risk substance use, found in 62% of users, was associated with younger age, being male, previous stressors, and suboptimal adherence. Our findings highlight the need for improved access to mental health and substance use services in HIV clinical settings.
  12. Rajasuriar R, Chong ML, Ross JL, Jiamsakul A, Avihingsanon A, Lee MP, et al.
    AIDS, 2023 Apr 01;37(5):823-835.
    PMID: 36728672 DOI: 10.1097/QAD.0000000000003474
    BACKGROUND: Depression and substance use (SU) disorders are prevalent among people with HIV (PWH) and impact health outcomes despite successful antiretroviral therapy (ART). We explored quality of life, functional ability and associated factors among PWH screened positive for depression and/or SU.

    METHODS: This cross-sectional study recruited adult PWH during routine follow-up at five HIV clinical sites in the Asia-Pacific region. Participants were screened for depression using Patient Health Questionnaire-9 and SU using Alcohol, Smoking, and Substance Involvement Screening Test (ASSIST). Quality of life (QoL) was assessed with WHOQOL-HIV BREF and functional ability with World Health Organization Disability Assessment Schedule 2.0 (WHODAS 2.0). Factors associated with mean QoL and disability scores were analysed using linear regression.

    RESULTS: Of 864 PWH enrolled, 753 screened positive for depression or SU. The median (interquartile range, IQR) age was 38 (31-47) years and 97% were on ART. Overall mean WHOQOL-HIV BREF and WHODAS scores indicated greater impairment with increasing depressive symptom severity and SU risk. In multivariate analysis, PWH reporting previous trauma/stress (difference = 2.7, 95% confidence interval [CI] 1.5-3.9, P  

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