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  1. Wilting A, Cord A, Hearn AJ, Hesse D, Mohamed A, Traeholdt C, et al.
    PLoS One, 2010;5(3):e9612.
    PMID: 20305809 DOI: 10.1371/journal.pone.0009612
    The flat-headed cat (Prionailurus planiceps) is one of the world's least known, highly threatened felids with a distribution restricted to tropical lowland rainforests in Peninsular Thailand/Malaysia, Borneo and Sumatra. Throughout its geographic range large-scale anthropogenic transformation processes, including the pollution of fresh-water river systems and landscape fragmentation, raise concerns regarding its conservation status. Despite an increasing number of camera-trapping field surveys for carnivores in South-East Asia during the past two decades, few of these studies recorded the flat-headed cat.
  2. Tang CT, Chua EC, Chew QH, He YL, Si TM, Chiu HF, et al.
    Asia Pac Psychiatry, 2020 Dec;12(4):e12393.
    PMID: 32468725 DOI: 10.1111/appy.12393
    INTRODUCTION: Patterns of clinical use of long-acting injectable (LAI) antipsychotic drugs in many countries, especially in Asia, for treatment of patients diagnosed with chronic psychotic disorders including schizophrenia are not well established.

    METHODS: Within an extensive research consortium, we evaluated prescription rates for first- (FGA) and second-generation antipsychotic (SGA) LAI drugs and their clinical correlates among 3557 subjects diagnosed with schizophrenia across 15 Asian countries and region.

    RESULTS: Overall, an average of 17.9% (638/3557; range: 0.0%-44.9%) of treated subjects were prescribed LAI antipsychotics. Those given LAI vs orally administered agents were significantly older, had multiple hospitalizations, received multiple antipsychotics more often, at 32.4% higher doses, were more likely to manifest disorganized behavior or aggression, had somewhat superior psychosocial functioning and less negative symptoms, but were more likely to be hospitalized, with higher BMI, and more tremor. Being prescribed an FGA vs SGA LAI agent was associated with male sex, aggression, disorganization, hospitalization, multiple antipsychotics, higher doses, with similar risks of adverse neurological or metabolic effects. Rates of use of LAI antipsychotic drugs to treat patients diagnosed with schizophrenia varied by more than 40-fold among Asian countries and given to an average of 17.9% of treated schizophrenia patients. We identified the differences in the clinical profiles and treatment characteristics of patients who were receiving FGA-LAI and SGA-LAI medications.

    DISCUSSION: These findings behoove clinicians to be mindful when evaluating patients' need to be on LAI antipsychotics amidst multifaceted considerations, especially downstream adverse events such as metabolic and extrapyramidal side effects.

  3. Sim K, Yong KH, Chan YH, Tor PC, Xiang YT, Wang CY, et al.
    Int. J. Neuropsychopharmacol., 2011 Oct;14(9):1157-64.
    PMID: 21557883 DOI: 10.1017/S1461145711000563
    Recent studies indicate relatively high international rates of adjunctive psychotropic medication, including mood stabilizers, for patients with schizophrenia. Since such treatments are little studied in Asia, we examined the frequency of mood-stabilizer use and its clinical correlates among hospitalized Asian patients diagnosed with schizophrenia in 2001-2008. We evaluated usage rates of mood stabilizers with antipsychotic drugs, and associated factors, for in-patients diagnosed with DSM-IV schizophrenia in 2001, 2004 and 2008 in nine Asian regions: China, Hong Kong, India, Korea, Japan, Malaysia, Taiwan, Thailand, and Singapore. Overall, mood stabilizers were given to 20.4% (n=1377/6761) of hospitalized schizophrenia patients, with increased usage over time. Mood-stabilizer use was significantly and independently associated in multivariate logistic modeling with: aggressive behaviour, disorganized speech, year sampled (2008 vs. earlier), multiple hospitalizations, less negative symptoms, younger age, with regional variation (Japan, Hong Kong, Singapore>Taiwan or China). Co-prescription of adjunctive mood stabilizers with antipsychotics for hospitalized Asian schizophrenia patients increased over the past decade, and was associated with specific clinical characteristics. This practice parallels findings in other countries and illustrates ongoing tension between evidence-based practice vs. individualized, empirical treatment of psychotic disorders.
  4. Shuy YK, Santharan S, Chew QH, Lin SK, Ouyang WC, Chen CK, et al.
    J Clin Psychopharmacol, 2024 01 16;44(2):117-123.
    PMID: 38230861 DOI: 10.1097/JCP.0000000000001813
    BACKGROUND: As clinical practices with lithium salts for patients diagnosed with bipolar disorder (BD) are poorly documented in Asia, we studied the prevalence and clinical correlates of lithium use there to support international comparisons.

    METHODS: We conducted a cross-sectional study of use and dosing of lithium salts for BD patients across 13 Asian sites and evaluated bivariate relationships of lithium treatment with clinical correlates followed by multivariate logistic regression modeling.

    RESULTS: In a total of 2139 BD participants (52.3% women) of mean age 42.4 years, lithium salts were prescribed in 27.3% of cases overall, varying among regions from 3.20% to 59.5%. Associated with lithium treatment were male sex, presence of euthymia or mild depression, and a history of seasonal mood change. Other mood stabilizers usually were given with lithium, often at relatively high doses. Lithium use was associated with newly emerging and dose-dependent risk of tremors as well as risk of hypothyroidism. We found no significant differences in rates of clinical remission or of suicidal behavior if treatment included lithium or not.

    CONCLUSIONS: Study findings clarify current prevalence, dosing, and clinical correlates of lithium treatment for BD in Asia. This information should support clinical decision-making regarding treatment of BD patients and international comparisons of therapeutic practices.

  5. Rupasinghe D, Kiertiburanakul S, Kamarulzaman A, Zhang F, Kumarasamy N, Chaiwarith R, et al.
    HIV Med, 2020 07;21(6):397-402.
    PMID: 31852025 DOI: 10.1111/hiv.12836
    OBJECTIVES: Early mortality among those still initiating antiretroviral therapy (ART) with advanced stages of HIV infection in resource-limited settings remains high despite recommendations for universal HIV treatment. We investigated risk factors associated with early mortality in people living with HIV (PLHIV) starting ART at low CD4 levels in the Asia-Pacific.

    METHODS: PLHIV enrolled in the Therapeutics, Research, Education and AIDS Training in Asia (TREAT Asia) HIV Observational Database (TAHOD) who initiated ART with a CD4 count  1 year were censored at 12 months. Competing risk regression was used to analyse risk factors with loss to follow-up as a competing risk.

    RESULTS: A total of 1813 PLHIV were included in the study, of whom 74% were male. With 73 (4%) deaths, the overall first-year mortality rate was 4.27 per 100 person-years (PY). Thirty-eight deaths (52%) were AIDS-related, 10 (14%) were immune reconstituted inflammatory syndrome (IRIS)-related, 13 (18%) were non-AIDS-related and 12 (16%) had an unknown cause. Risk factors included having a body mass index (BMI)  100 cells/μL: SHR 0.12; 95% CI 0.05-0.26) was associated with reduced hazard for mortality compared to CD4 count ≤ 25 cells/μL.

    CONCLUSIONS: Fifty-two per cent of early deaths were AIDS-related. Efforts to initiate ART at CD4 counts > 50 cell/μL are associated with improved short-term survival rates, even in those with late stages of HIV disease.

  6. Rupasinghe D, Choi JY, Yunihastuti E, Kiertiburanakul S, Ross J, Ly PS, et al.
    J Med Virol, 2022 Nov;94(11):5451-5464.
    PMID: 35869413 DOI: 10.1002/jmv.28019
    Liver disease is a growing burden among people living with HIV (PLHIV) in resource-limited settings. As an indicator of liver disease, risk factors of high alanine aminotransferase (ALT) and cirrhosis were assessed among PLHIV in the TREAT Asia HIV Observational Database (TAHOD). Patients on combination antiretroviral therapy (cART) with a pre-cART ALT measurement and at least one follow-up ALT measurement were included. Factors associated with high ALT (ALT levels > 5 times its upper limit of normal) were analyzed using repeated measure logistic regression over a 10-year follow-up period. Liver cirrhosis was defined as having an AST to Platelet Ratio Index score > 1.5, fibrosis-4 score > 3.25, or a clinical diagnosis of cirrhosis. Cox regression analysis stratified by site was used to analyze factors associated with cirrhosis among those in follow-up after 2015. Of 5182 patients, 101 patients (1.9%) had high ALT levels with hepatitis C virus (HCV) antibody positive (odds ratio [OR]: 4.98, 95% confidence interval [CI]: 2.82-8.77, p 
  7. Ross J, Jiamsakul A, Kumarasamy N, Azwa I, Merati TP, Do CD, et al.
    HIV Med, 2021 Mar;22(3):201-211.
    PMID: 33151020 DOI: 10.1111/hiv.13006
    OBJECTIVES: To assess second-line antiretroviral therapy (ART) virological failure and HIV drug resistance-associated mutations (RAMs), in support of third-line regimen planning in Asia.

    METHODS: Adults > 18 years of age on second-line ART for ≥ 6 months were eligible. Cross-sectional data on HIV viral load (VL) and genotypic resistance testing were collected or testing was conducted between July 2015 and May 2017 at 12 Asia-Pacific sites. Virological failure (VF) was defined as VL > 1000 copies/mL with a second VL > 1000 copies/mL within 3-6 months. FASTA files were submitted to Stanford University HIV Drug Resistance Database and RAMs were compared against the IAS-USA 2019 mutations list. VF risk factors were analysed using logistic regression.

    RESULTS: Of 1378 patients, 74% were male and 70% acquired HIV through heterosexual exposure. At second-line switch, median [interquartile range (IQR)] age was 37 (32-42) years and median (IQR) CD4 count was 103 (43.5-229.5) cells/µL; 93% received regimens with boosted protease inhibitors (PIs). Median duration on second line was 3 years. Among 101 patients (7%) with VF, CD4 count > 200 cells/µL at switch [odds ratio (OR) = 0.36, 95% confidence interval (CI): 0.17-0.77 vs. CD4 ≤ 50) and HIV exposure through male-male sex (OR = 0.32, 95% CI: 0.17-0.64 vs. heterosexual) or injecting drug use (OR = 0.24, 95% CI: 0.12-0.49) were associated with reduced VF. Of 41 (41%) patients with resistance data, 80% had at least one RAM to nonnucleoside reverse transcriptase inhibitors (NNRTIs), 63% to NRTIs, and 35% to PIs. Of those with PI RAMs, 71% had two or more.

    CONCLUSIONS: There were low proportions with VF and significant RAMs in our cohort, reflecting the durability of current second-line regimens.

  8. Rajaratnam K, Xiang YT, Tripathi A, Chiu HF, Si TM, Chee KY, et al.
    J Clin Psychopharmacol, 2016 Dec;36(6):716-719.
    PMID: 27753726
    In this study, we sought to examine factors associated with dosing of antidepressants (ADs) in Asia. Based on reported data and clinical experience, we hypothesized that doses of ADs would be associated with demographic and clinical factors and would increase over time. This cross-sectional, pharmacoepidemiological study analyzed data collected within the Research Study on Asian Psychotropic Prescription Pattern for Antidepressants from 4164 participants in 10 Asian countries, using univariate and multivariate methods. The AD doses varied by twofold among countries (highest in PR China and RO Korea, lowest in Singapore and Indonesia), and averaged 124 (120-129) mg/d imipramine-equivalents. Average daily doses increased by 12% between 2004 and 2013. Doses were significantly higher among hospitalized patients and ranked by diagnosis: major depression > anxiety disorders > bipolar disorder, but were not associated with private/public or psychiatric/general-medical settings, nor with age, sex, or cotreatment with a mood stabilizer. In multivariate modeling, AD-dose remained significantly associated with major depressive disorder and being hospitalized. Doses of ADs have increased somewhat in Asia and were higher when used for major depression or anxiety disorders than for bipolar depression and for hospitalized psychiatric patients.
  9. Rajaratnam K, Xiang YT, Tripathi A, Chiu HF, Si TM, Chee KY, et al.
    J Clin Psychopharmacol, 2017 Apr;37(2):255-259.
    PMID: 28146001 DOI: 10.1097/JCP.0000000000000670
    OBJECTIVE: As most reports concerning treatment with combinations of mood stabilizer (MS) with antidepressant (AD) drugs are based in the West, we surveyed characteristics of such cotreatment in 42 sites caring for the mentally ill in 10 Asian countries.
    METHODS: This cross-sectional, pharmacoepidemiologic study used 2004 and 2013 data from the REAP-AD (Research Study on Asian Psychotropic Prescription Patterns for Antidepressants) to evaluate the rates and doses of MSs given with ADs and associated factors in 4164 psychiatric patients, using standard bivariate methods followed by multivariable logistic regression modeling.
    RESULTS: Use of MS + AD increased by 104% (5.5% to 11.2%) between 2004 and 2013 and was much more associated with diagnosis of bipolar disorder than major depression or anxiety disorder, as well as with hospitalization > outpatient care, psychiatric > general-medical programs, and young age (all P < 0.001), but not with country, sex, or AD dose.

    CONCLUSIONS: The findings provide a broad picture of contemporary use of MSs with ADs in Asia, support predictions that such treatment increased in recent years, and was associated with diagnosis of bipolar disorder, treatment in inpatient and psychiatric settings, and younger age.
  10. Pasayan MKU, S Mationg ML, Boettiger D, Lam W, Zhang F, Ku SW, et al.
    J Acquir Immune Defic Syndr, 2019 04 01;80(4):436-443.
    PMID: 30550488 DOI: 10.1097/QAI.0000000000001933
    BACKGROUND: Mycobacterium avium complex prophylaxis is recommended for patients with advanced HIV infection. With the decrease in incidence of disseminated Mycobacterium avium complex infection and the availability of antiretroviral therapy (ART), the benefits of macrolide prophylaxis were investigated. This study examined the impact of macrolide prophylaxis on AIDS-defining conditions and HIV-associated mortality in a cohort of HIV-infected patients on ART.

    METHODS: Patients from TREAT Asia HIV Observational Database (September 2015 data transfer) aged 18 years and older with a CD4 count <50 cells/mm at ART initiation were included. The effect of macrolide prophylaxis on HIV-associated mortality or AIDS-defining conditions (as a combined outcome) and HIV-associated mortality alone were evaluated using competing risk regression. Sensitivity analysis was conducted in patients with a CD4 <100 cells/mm at ART initiation.

    RESULTS: Of 1345 eligible patients, 10.6% received macrolide prophylaxis. The rate of the combined outcome was 7.35 [95% confidence interval (CI): 6.04 to 8.95] per 100 patient-years, whereas the rate of HIV-associated mortality was 3.14 (95% CI: 2.35 to 4.19) per 100 patient-years. Macrolide use was associated with a significantly decreased risk of HIV-associated mortality (hazard ratio 0.10, 95% CI: 0.01 to 0.80, P = 0.031) but not with the combined outcome (hazard ratio 0.86, 95% CI: 0.32 to 2.229, P = 0.764). Sensitivity analyses showed consistent results among patients with a CD4 <100 cells/mm at ART initiation.

    CONCLUSIONS: Macrolide prophylaxis is associated with improved survival among Asian HIV-infected patients with low CD4 cell counts and on ART. This study suggests the increased usage and coverage of macrolide prophylaxis among people living with HIV in Asia.

  11. Nájera F, Hearn AJ, Ross J, Ramírez Saldivar DA, Evans MN, Guerrero-Sánchez S, et al.
    J Vet Med Sci, 2017 Nov 17;79(11):1892-1898.
    PMID: 28904261 DOI: 10.1292/jvms.17-0259
    There is currently no available information regarding the veterinary management of Sunda clouded leopards (Neofelis diardi), either in captivity or in the wild. In this study, 12 Sunda clouded leopards were anesthetized between January 2008 and February 2014 for medical exams, and/or GPS-collaring. Seven wild-caught individuals were kept in captivity and 5 free-ranging animals were captured by cage traps. Two anesthesia combinations were used: medetomidine-ketamine (M-K) or tiletamine-zolazepam (T-Z). Atipamezole (0.2 mg/kg im) was used as an antagonist for medetomidine. Medetomidine (range: 0.039-0.054 mg/kg) and ketamine (range: 3-4.39 mg/kg) were administered during 5 immobilizations, resulting in median induction times of 7 min. After a median anesthesia time of 56 min, atipamezole was injected, observing effects of antagonism at a median time of 12 min. T-Z (range: 6.8-10.8 mg/kg) was administered on 7 occasions. Median induction times observed with this combination were shorter than with M-K (4 min vs 7 min; P=0.04), and anesthesia and recovery times were significantly longer (244 and 35 min vs 56 and 16 min, respectively; P=0.02). Lower heart rates were measured in the M-K group, while lower rectal temperatures were found in the T-Z group. Both combinations resulted in safe and reliable immobilizations, although given the favorable anesthesia and recovery times of M-K, we recommend this approach over T-Z for the veterinary handling of Sunda clouded leopards.
  12. Nájera F, Hearn AJ, Ross J, Nathan S, Revuelta L
    Vet Res Commun, 2014 Sep;38(3):265-9.
    PMID: 24839119 DOI: 10.1007/s11259-014-9605-2
    Box-traps for capturing wild cats are widely used by researchers since it is one of the most effective methods for trapping these species. Although they are extensively utilised, the effects on the physiology of trapped felids remain unclear. Researchers frequently make judgements regarding the safety of such capture devices by examination of external injuries but often fail to take into consideration other physiological parameters. To assess the effects of capture events on selected serum biochemistry values of free-ranging Bornean leopard cats (Prionailurus bengalensis borneoensis) six free-ranging leopard cats (four males, two females) were trapped by using box-traps in Sabah, Malaysian Borneo. Blood was collected by jugular venipucture after chemical immobilization with a mixture of tiletamine and zolazepam. Blood was analysed for 17 serum biochemistry parameters. The most consistent and significantly higher value found in both sexes was aspartate aminotransferase (AST), followed by high mean value of alanine aminotransferase (ALT). Both mean values exceeded the upper limit of the reference range for captive leopard cats. These results demonstrate that captured leopard cats by box-traps undergo physical exertion and consequently some type of muscle injury/damage. Researchers and wildlife managers should be aware of the physiological response of trapped felids when using box-traps. Devices that facilitate the prompt removal of leopard cats from the traps would be useful for researchers to avoid further damage while live trapping this species.
  13. Mauldin WP, Ross JA
    Stud Fam Plann, 1994 Mar-Apr;25(2):77-95.
    PMID: 8059448 DOI: 10.2307/2138086
    What is the likelihood that each of the 37 developing countries with populations of 15 million or more in 1990 will reach replacement fertility by the year 2015? These countries have a combined population of 3.9 billion, 91 percent of the population of all developing countries. For this article, a composite index was used as the basis for predicting future levels of total fertility. The index was constructed from socioeconomic variables (life expectancy at birth, infant mortality rates, percent adult literacy, ratio of children enrolled in primary or secondary school, percent of the labor force in nonagricultural occupations, gross national product per capita, and percent of the population living in urban areas), total fertility rates for the years 1985-90, total fertility rate decline from 1960-65 to 1985-90, family planning program effort scores in 1989, and the level of contraceptive prevalence in 1990. Eight countries are classified as certain to reach replacement fertility by 2015, and an additional thirteen probably will also. Five countries are classified as possibly reaching replacement fertility, and eleven as unlikely to do so.
  14. Loo LWJ, Chew QH, Lin SK, Yang SY, Ouyang WC, Chen CK, et al.
    PMID: 37068038 DOI: 10.1097/JCP.0000000000001693
    BACKGROUND: Pharmacoepidemiological studies of clozapine use to treat bipolar disorder (BD), especially in Asia, are rare, although they can provide insights into associated clinical characteristics and support international comparisons of indications and drug dosing.

    METHODS: We examined the prevalence and clinical correlates of clozapine treatment for BD in 13 Asian countries and regions (China, Hong Kong SAR, India, Indonesia, Japan, Korea, Malaysia, Myanmar, Pakistan, Singapore, Sri Lanka, Taiwan, and Thailand) within an Asian Prescription Patterns Research Consortium. We compared BD patients treated with clozapine or not in initial bivariate comparisons followed by multivariable logistic regression modeling.

    RESULTS: Clozapine was given to 2.13% of BD patients overall, at a mean daily dose of 275 (confidence interval, 267-282) chlorpromazine-equivalent mg/day. Patients receiving clozapine were older, more likely males, hospitalized, currently manic, and given greater numbers of mood-stabilizing and antipsychotic drugs in addition to clozapine. Logistic regression revealed that older age, male sex, current mania, and greater number of other antipsychotics remained significantly associated with clozapine treatment. Clozapine use was not associated with depressed mood, remission of illness, suicidal risk, or electroconvulsive treatment within the previous 12 months.

    CONCLUSIONS: The identified associations of clozapine use with particular clinical features call for vigilance in personalized clinical monitoring so as to optimize clinical outcomes of BD patients and to limit risks of adverse effects of polytherapy.

  15. Lim WK, Chew QH, He YL, Si TM, Chiu FH, Xiang YT, et al.
    Hum Psychopharmacol, 2020 11;35(6):1-7.
    PMID: 32738085 DOI: 10.1002/hup.2752
    OBJECTIVE: Studies examining coprescription and dosages of mood stabilizers (MSs) with antipsychotics for psychotic disorders are infrequent. Based on sparse extant data and clinical experience, we hypothesized that adjunctive MS use would be associated with certain demographic (e.g., younger age), clinical factors (e.g., longer illness duration), and characteristics of antipsychotic treatment (e.g., multiple or high antipsychotic doses).

    METHODS: Within an Asian research consortium focusing on pharmaco-epidemiological factors in schizophrenia, we evaluated rates of MS coprescription, including high doses (>1000 mg/day lithium-equivalents) and clinical correlates.

    RESULTS: Among 3557 subjects diagnosed with schizophrenia in 14 Asian countries, MSs were coprescribed with antipsychotics in 13.6% (n = 485) of the sample, with 10.9% (n = 53) on a high dose. Adjunctive MS treatment was associated (all p < 0.005) with demographic (female sex and younger age), setting (country and hospitalization), illness (longer duration, more hospitalizations, non-remission of illness, behavioral disorganization, aggression, affective symptoms, and social-occupational dysfunction), and treatment-related factors (higher antipsychotic dose, multiple antipsychotics, higher body mass index, and greater sedation). Patients given high doses of MSs had a less favorable illness course, more behavioral disorganization, poorer functioning, and higher antipsychotic doses.

    CONCLUSIONS: Schizophrenia patients receiving adjunctive MS treatment in Asian psychiatric centers are more severely ill and less responsive to simpler treatment regimens.

  16. Leadley RM, Lang S, Misso K, Bekkering T, Ross J, Akiyama T, et al.
    Orphanet J Rare Dis, 2014;9:173.
    PMID: 25404155 DOI: 10.1186/s13023-014-0173-x
    Morquio A (MPS IVA) is a rare disease characterised by a deficiency of N-acetylgalactosamine-6 sulfatase (GALNS) and presenting with short stature, abnormal gait, cervical spine instability and shortened lifespan.
  17. Ku SW, Jiamsakul A, Joshi K, Pasayan MKU, Widhani A, Chaiwarith R, et al.
    J Int AIDS Soc, 2019 Mar;22(3):e25264.
    PMID: 30924281 DOI: 10.1002/jia2.25264
    INTRODUCTION: Cotrimoxazole (CTX) is recommended as prophylaxis against Pneumocystis jiroveci pneumonia, malaria and other serious bacterial infections in HIV-infected patients. Despite its in vitro activity against Mycobacterium tuberculosis, the effects of CTX preventive therapy on tuberculosis (TB) remain unclear.

    METHODS: Adults living with HIV enrolled in a regional observational cohort in Asia who had initiated combination antiretroviral therapy (cART) were included in the analysis. Factors associated with new TB diagnoses after cohort entry and survival after cART initiation were analysed using Cox regression, stratified by site.

    RESULTS: A total of 7355 patients from 12 countries enrolled into the cohort between 2003 and 2016 were included in the study. There were 368 reported cases of TB after cohort entry with an incidence rate of 0.99 per 100 person-years (/100 pys). Multivariate analyses adjusted for viral load (VL), CD4 count, body mass index (BMI) and cART duration showed that CTX reduced the hazard for new TB infection by 28% (HR 0.72, 95% CI l 0.56, 0.93). Mortality after cART initiation was 0.85/100 pys, with a median follow-up time of 4.63 years. Predictors of survival included age, female sex, hepatitis C co-infection, TB diagnosis, HIV VL, CD4 count and BMI.

    CONCLUSIONS: CTX was associated with a reduction in the hazard for new TB infection but did not impact survival in our Asian cohort. The potential preventive effect of CTX against TB during periods of severe immunosuppression should be further explored.

  18. Kim JH, Jiamsakul A, Kiertiburanakul S, Huy BV, Khusuwan S, Kumarasamy N, et al.
    PLoS One, 2022;17(3):e0264157.
    PMID: 35353840 DOI: 10.1371/journal.pone.0264157
    The use of holding regimens for people living with HIV (PLWH) without effective antiretroviral options can have effects on outcomes and future treatment options. We aimed to investigate the use of holding regimens for PLWH in Asian countries. Data from adults enrolled in routine HIV care in IeDEA Asia-Pacific cohorts were included. Individuals were considered to be on holding regimen if they had been on combination antiretroviral therapy for at least 6 months, had two confirmed viral loads (VL) ≥1000 copies/mL, and had remained on the same medications for at least 6 months. Survival time was analyzed using Fine and Gray's competing risk regression. Factors associated with CD4 changes and VL <1000 copies/mL were analyzed using linear regression and logistic regression, respectively. A total of 425 PLWH (72.9% male; 45.2% high-income and 54.8% low-to-middle-income country) met criteria for being on a holding regimen. From high-income countries, 63.0% were on protease inhibitors (PIs); from low-to-middle-income countries, 58.4% were on non-nucleoside reverse transcriptase inhibitors (NNRTIs); overall, 4.5% were on integrase inhibitors. The combination of lamivudine, zidovudine, and efavirenz was the most commonly used single regimen (n = 46, 10.8%), followed by lamivudine, zidovudine, and nevirapine (n = 37, 8.7%). Forty-one PLWH (9.7%) died during follow-up (mortality rate 2.0 per 100 person-years). Age >50 years compared to age 31-40 years (sub-hazard ratio [SHR] 3.29, 95% CI 1.45-7.43, p = 0.004), and VL ≥1000 copies/ml compared to VL <1000 copies/mL (SHR, 2.14, 95% CI 1.08-4.25, p = 0.029) were associated with increased mortality, while higher CD4 counts were protective. In our Asia regional cohort, there was a diversity of holding regimens, and the patterns of PI vs. NNRTI use differed by country income levels. Considering the high mortality rate of PLWH with holding regimen, efforts to extend accessibility to additional antiretroviral options are needed in our region.
  19. Khuon D, Rupasinghe D, Saphonn V, Kwong TS, Widhani A, Chaiwarith R, et al.
    HIV Med, 2023 Feb;24(2):139-152.
    PMID: 35748404 DOI: 10.1111/hiv.13351
    BACKGROUND: Non-Asian body mass index (BMI) classifications are commonly used as a risk factor for high fasting blood glucose (FBG). We investigated the incidence and factors associated with high FBG among people living with HIV in the Asia-Pacific region, using a World Health Organization BMI classification specific to Asian populations.

    METHODS: This study included people living with HIV enrolled in a longitudinal cohort study from 2003 to 2019, receiving antiretroviral therapy (ART), and without prior tuberculosis. BMI at ART initiation was categorized using Asian BMI classifications: underweight (<18.5 kg/m2 ), normal (18.5-22.9 kg/m2 ), overweight (23-24.9 kg/m2 ), and obese (≥25 kg/m2 ). High FBG was defined as a single post-ART FBG measurement ≥126 mg/dL. Factors associated with high FBG were analyzed using Cox regression models stratified by site.

    RESULTS: A total of 3939 people living with HIV (63% male) were included. In total, 50% had a BMI in the normal weight range, 23% were underweight, 13% were overweight, and 14% were obese. Median age at ART initiation was 34 years (interquartile range 29-41). Overall, 8% had a high FBG, with an incidence rate of 1.14 per 100 person-years. Factors associated with an increased hazard of high FBG included being obese (≥25 kg/m2 ) compared with normal weight (hazard ratio [HR] = 1.79; 95% confidence interval [CI] 1.31-2.44; p 25 kg/m2 were at increased risk of high FBG. This indicates that regular assessments should be performed in those with high BMI, irrespective of the classification used.

  20. Kabir TD, Leigh RJ, Tasena H, Mellone M, Coletta RD, Parkinson EK, et al.
    Aging (Albany NY), 2016 08;8(8):1608-35.
    PMID: 27385366 DOI: 10.18632/aging.100987
    Senescent cancer-associated fibroblasts (CAF) develop a senescence-associated secretory phenotype (SASP) that is believed to contribute to cancer progression. The mechanisms underlying SASP development are, however, poorly understood. Here we examined the functional role of microRNA in the development of the SASP in normal fibroblasts and CAF. We identified a microRNA, miR-335, up-regulated in the senescent normal fibroblasts and CAF and able to modulate the secretion of SASP factors and induce cancer cell motility in co-cultures, at least in part by suppressing the expression of phosphatase and tensin homologue (PTEN). Additionally, elevated levels of cyclo-oxygenase 2 (PTGS2; COX-2) and prostaglandin E2 (PGE2) secretion were observed in senescent fibroblasts, and inhibition of COX-2 by celecoxib reduced the expression of miR-335, restored PTEN expression and decreased the pro-tumourigenic effects of the SASP. Collectively these data demonstrate the existence of a novel miRNA/PTEN-regulated pathway modulating the inflammasome in senescent fibroblasts.
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