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  1. Boettiger DC, Nguyen VK, Durier N, Bui HV, Heng Sim BL, Azwa I, et al.
    J. Acquir. Immune Defic. Syndr., 2015 Feb 1;68(2):186-95.
    PMID: 25590271 DOI: 10.1097/QAI.0000000000000411
    Roughly 4% of the 1.25 million patients on antiretroviral therapy (ART) in Asia are using second-line therapy. To maximize patient benefit and regional resources, it is important to optimize the timing of second-line ART initiation and use the most effective compounds available.
  2. Jiamsakul A, Chaiwarith R, Durier N, Sirivichayakul S, Kiertiburanakul S, Van Den Eede P, et al.
    J. Med. Virol., 2016 Feb;88(2):234-43.
    PMID: 26147742 DOI: 10.1002/jmv.24320
    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 vircoType(TM) 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.
  3. Durier N, Yunihastuti E, Ruxrungtham K, Kinh NV, Kamarulzaman A, Boettiger D, et al.
    J. Viral Hepat., 2017 03;24(3):187-196.
    PMID: 27917597 DOI: 10.1111/jvh.12630
    Data on markers of hepatitis C virus (HCV) disease in HIV-HCV-coinfected patients in resource-limited settings are scarce. We assessed HCV RNA, HCV genotype (GT), IL28B GT and liver fibrosis (FibroScan® ) in 480 HIV-infected patients with positive HCV antibody in four HIV treatment centres in South-East Asia. We enrolled 165 (34.4%) patients in Jakarta, 158 (32.9%) in Bangkok, 110 (22.9%) in Hanoi and 47 (9.8%) in Kuala Lumpur. Overall, 426 (88.8%) were male, the median (IQR) age was 38.1 (34.7-42.5) years, 365 (76.0%) reported HCV exposure through injecting drug use, and 453 (94.4%) were on combination antiretroviral therapy. The median (IQR) CD4 count was 446 (325-614) cells/mm3 and 208 (94.1%) of 221 patients tested had HIV-1 RNA <400 copies/mL. A total of 412 (85.8%) had detectable HCV RNA, at a median (IQR) of 6.2 (5.4-6.6) log10 IU/mL. Among 380 patients with HCV GT, 223 (58.7%) had GT1, 97 (25.5%) had GT3, 43 (11.3%) had GT6, eight (2.1%) had GT4, two (0.5%) had GT2, and seven (1.8%) had indeterminate GT. Of 222 patients with IL28B testing, 189 (85.1%) had rs12979860 CC genotype, and 199 (89.6%) had rs8099917 TT genotype. Of 380 patients with FibroScan® , 143 (37.6%) had no/mild liver fibrosis (F0-F1), 83 (21.8%) had moderate fibrosis (F2), 74 (19.5%) had severe fibrosis (F3), and 79 (20.8%) had cirrhosis (F4). One patient (0.3%) had FibroScan® failure. In conclusion, a high proportion of HIV-HCV-coinfected patients had chronic HCV infection. HCV GT1 was predominant, and 62% of patients had liver disease warranting prompt treatment (≥F2).
  4. Kariminia A, Durier N, Jourdain G, Saghayam S, Do CV, Nguyen LV, et al.
    J. Acquir. Immune Defic. Syndr., 2014 Sep 1;67(1):71-6.
    PMID: 24872132 DOI: 10.1097/QAI.0000000000000227
    To evaluate the value of time-updated weight and height in predicting clinical progression, and immunological and virological failure in children receiving combination antiretroviral therapy (cART).
  5. Do TC, Boettiger D, Law M, Pujari S, Zhang F, Chaiwarith R, et al.
    HIV Med., 2016 08;17(7):542-9.
    PMID: 27430354 DOI: 10.1111/hiv.12358
    OBJECTIVES: The aim of the study was to assess the prevalence and characteristics associated with current smoking in an Asian HIV-positive cohort, to calculate the predictive risks of cardiovascular disease (CVD), coronary heart disease (CHD) and myocardial infarction (MI), and to identify the impact that simulated interventions may have.

    METHODS: Logistic regression analysis was used to distinguish associated current smoking characteristics. Five-year predictive risks of CVD, CHD and MI and the impact of simulated interventions were calculated utilizing the Data Collection on Adverse Effects of Anti-HIV Drugs Study (D:A:D) algorithm.

    RESULTS: Smoking status data were collected from 4274 participants and 1496 of these had sufficient data for simulated intervention calculations. Current smoking prevalence in these two groups was similar (23.2% vs. 19.9%, respectively). Characteristics associated with current smoking included age > 50 years compared with 30-39 years [odds ratio (OR) 0.65; 95% confidence interval (CI) 0.51-0.83], HIV exposure through injecting drug use compared with heterosexual exposure (OR 3.03; 95% CI 2.25-4.07), and receiving antiretroviral therapy (ART) at study sites in Singapore, South Korea, Malaysia, Japan and Vietnam in comparison to Thailand (all OR > 2). Women were less likely to smoke than men (OR 0.11; 95% CI 0.08-0.14). In simulated interventions, smoking cessation demonstrated the greatest impact in reducing CVD and CHD risk and closely approximated the impact of switching from abacavir to an alternate antiretroviral in the reduction of 5-year MI risk.

    CONCLUSIONS: Multiple interventions could reduce CVD, CHD and MI risk in Asian HIV-positive patients, with smoking cessation potentially being the most influential.

  6. Prasitsuebsai W, Sethaputra C, Lumbiganon P, Hansudewechakul R, Chokephaibulkit K, Truong KH, et al.
    AIDS Care, 2018 06;30(6):727-733.
    PMID: 29336591 DOI: 10.1080/09540121.2018.1425363
    We studied behavioral risks among HIV-infected and uninfected adolescents using an audio computer-assisted self-interview. A prospective cohort study was initiated between 2013 and 2014 in Malaysia, Thailand, and Vietnam. HIV-infected adolescents were matched to uninfected adolescents (4:1) by sex and age group (12-14 and 15-18 years). We enrolled 250 HIV-infected (48% male; median age 14.5 years; 93% perinatally infected) and 59 uninfected (51% male; median age 14.1 years) adolescents. At enrollment, HIV-infected adolescents were on antiretroviral therapy (ART) for a median (IQR) of 7.5 (4.7-10.2) years, and 14% had HIV-RNA >1000 copies/mL; 19% reported adherence <80%. Eighty-four (34%) HIV-infected and 26 (44%) uninfected adolescents reported having ever smoked cigarettes or drunk alcohol (p = 0.13); 10% of HIV-infected and 17% of uninfected adolescents reported having initiated sexual activity; 6 of the HIV-infected adolescents had HIV-RNA >1000 copies/mL. Risk behaviors were common among adolescents, with few differences between those with and without HIV.
  7. Chen M, Wong WW, Law MG, Kiertiburanakul S, Yunihastuti E, Merati TP, et al.
    PLoS ONE, 2016;11(3):e0150512.
    PMID: 26933963 DOI: 10.1371/journal.pone.0150512
    BACKGROUND: We assessed the effects of hepatitis B (HBV) or hepatitis C (HCV) co-infection on outcomes of antiretroviral therapy (ART) in HIV-infected patients enrolled in the TREAT Asia HIV Observational Database (TAHOD), a multi-center cohort of HIV-infected patients in the Asia-Pacific region.

    METHODS: Patients testing HBs antigen (Ag) or HCV antibody (Ab) positive within enrollment into TAHOD were considered HBV or HCV co-infected. Factors associated with HBV and/or HCV co-infection were assessed by logistic regression models. Factors associated with post-ART HIV immunological response (CD4 change after six months) and virological response (HIV RNA <400 copies/ml after 12 months) were also determined. Survival was assessed by the Kaplan-Meier method and log rank test.

    RESULTS: A total of 7,455 subjects were recruited by December 2012. Of patients tested, 591/5656 (10.4%) were HBsAg positive, 794/5215 (15.2%) were HCVAb positive, and 88/4966 (1.8%) were positive for both markers. In multivariate analysis, HCV co-infection, age, route of HIV infection, baseline CD4 count, baseline HIV RNA, and HIV-1 subtype were associated with immunological recovery. Age, route of HIV infection, baseline CD4 count, baseline HIV RNA, ART regimen, prior ART and HIV-1 subtype, but not HBV or HCV co-infection, affected HIV RNA suppression. Risk factors affecting mortality included HCV co-infection, age, CDC stage, baseline CD4 count, baseline HIV RNA and prior mono/dual ART. Shortest survival was seen in subjects who were both HBV- and HCV-positive.

    CONCLUSION: In this Asian cohort of HIV-infected patients, HCV co-infection, but not HBV co-infection, was associated with lower CD4 cell recovery after ART and increased mortality.

  8. Jeong SJ, Italiano C, Chaiwarith R, Ng OT, Vanar S, Jiamsakul A, et al.
    AIDS Res. Hum. Retroviruses, 2016 Mar;32(3):255-61.
    PMID: 26414065 DOI: 10.1089/AID.2015.0058
    Many HIV-infected individuals do not enter health care until late in the infection course. Despite encouraging earlier testing, this situation has continued for several years. We investigated the prevalence of late presenters and factors associated with late presentation among HIV-infected patients in an Asian regional cohort. This cohort study included HIV-infected patients with their first positive HIV test during 2003-2012 and CD4 count and clinical status data within 3 months of that test. Factors associated with late presentation into care (CD4 count <200 cells/μl or an AIDS-defining event within ±3 months of first positive HIV test) were analyzed in a random effects logistic regression model. Among 3,744 patients, 2,681 (72%) were late presenters. In the multivariable model, older patients were more likely to be late presenters than younger (≤30 years) patients [31-40, 41-50, and ≥51 years: odds ratio (OR) = 1.57, 95% confidence interval (CI) 1.31-1.88; OR = 2.01, 95% CI 1.58-2.56; and OR = 1.69, 95% CI 1.23-2.31, respectively; all p ≤ 0.001]. Injecting drug users (IDU) were more likely (OR = 2.15, 95% CI 1.42-3.27, p < 0.001) and those with homosexual HIV exposure were less likely (OR = 0.45, 95% CI 0.35-0.58, p < 0.001) to be late presenters compared to those with heterosexual HIV exposure. Females were less likely to be late presenters (OR = 0.44, 95% CI 0.36-0.53, p < 0.001). The year of first positive HIV test was not associated with late presentation. Efforts to reduce the patients who first seek HIV care at the late stage are needed. The identified risk factors associated with late presentation should be utilized in formulating targeted public health intervention to improve earlier entry into HIV care.
  9. Kiertiburanakul S, Boettiger D, Lee MP, Omar SF, Tanuma J, Ng OT, et al.
    J Int AIDS Soc, 2014;17:18804.
    PMID: 24598459 DOI: 10.7448/IAS.17.1.18804
    Although antiretroviral therapy (ART) has been rapidly scaled up in Asia, most HIV-positive patients in the region still present with late-stage HIV disease. We aimed to determine trends of pre-ART CD4 levels over time in Asian HIV-positive patients and to determine factors associated with late ART initiation.
  10. Ku NS, Jiamsakul A, Ng OT, Yunihastuti E, Cuong do D, Lee MP, et al.
    Medicine (Baltimore), 2016 Aug;95(32):e4570.
    PMID: 27512885 DOI: 10.1097/MD.0000000000004570
    Elevated CD8 counts with combination antiretroviral therapy (cART) initiation may be an early warning indicator for future treatment failure. Thus, we investigated whether elevated CD8 counts were associated with virological failure (VF) in the first 4 years of cART in Asian HIV-infected patients in a multicenter regional cohort.We included patients from the TREAT Asia HIV Observational Database (TAHOD). Patients were included in the analysis if they started cART between 1996 and 2013 with at least one CD8 measurement within 6 months prior to cART initiation and at least one CD8 and viral load (VL) measurement beyond 6 months after starting cART. We defined VF as VL ≥400 copies/mL after 6 months on cART. Elevated CD8 was defined as CD8 ≥1200 cells/μL. Time to VF was modeled using Cox regression analysis, stratified by site.In total, 2475 patients from 19 sites were included in this analysis, of whom 665 (27%) experienced VF in the first 4 years of cART. The overall rate of VF was 12.95 per 100 person-years. In the multivariate model, the most recent elevated CD8 was significantly associated with a greater hazard of VF (HR = 1.35, 95% CI 1.14-1.61; P = 0.001). However, the sensitivity analysis showed that time-lagged CD8 measured at least 6 months prior to our virological endpoint was not statistically significant (P = 0.420).This study indicates that the relationship between the most recent CD8 count and VF was possibly due to the CD8 cells reacting to the increase in VL rather than causing the VL increase itself. However, CD8 levels may be a useful indicator for VF in HIV-infected patients after starting cART.
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