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Impact of drug classes and treatment availability on the rate of antiretroviral treatment change in the TREAT Asia HIV Observational Database (TAHOD)
Preeyaporn Srasuebkul, Alexandra Calmy, Jialun Zhou, Nagalingeswaran Kumarasamy, Matthew Law, Poh Lim, The TREAT Asia HIV Observational Database
AIDS Research and Therapy , 2007, DOI: 10.1186/1742-6405-4-18
Abstract: Rates of ART changes were examined in patients who started first line triple or more ART combination in TAHOD, and had at least one follow-up visit. Rates of ART changes were summarised per follow-up year, and factors associated with changes assessed using random-effect Poisson regression. The Kaplan-Meier method was used to determine durations of patients in their first, second and third regimen.A total of 1846 patients initiated an ART combination with at least three drugs. Median follow up time for the first treatment was 3.2 years. The overall rate of ART change was 29 per 100-person-year.In univariate analyses, rate of treatment change was significantly associated with exposure category, the country income category, the drug class combination, calendar year and the number of combinations. In multivariate analysis, compared to d4T/3TC/NVP, starting ART with another NNRTI-containing regimen, with PI only or with a triple NRTI regimen was associated with a higher risk of combination change (relative risk (RR) 1.6 (95% CI 1.64 – 1.96), p < 0.001, RR 3.39 (2.76 – 4.16) p < 0.001, RR 6.37 (4.51 – 9.00), p < 0.001). Being on a second or a third combination regimen was also associated with a decreased rate of ART change, compared with first ART combination (RR 0.82 (0.68 – 0.99), p = 0.035, RR 0.77 (0.61 – 0.97), p = 0.024). Sites with fewer than 12 drugs used had an increased rate of treatment changes (1.31 (1.13 – 1.51), p < 0.001). Injecting drug users, and other/unknown exposure was found to increase rate of treatment change (1.24 (1.00 – 1.54), p = 0.055). Percentages of patients who stopped treatment due to adverse events were 31, 27 and 32 in 1st, 2nd and 3rd treatment combinations, respectively.Our study suggests that drug availability impacts on ART prescription patterns. Our data, reflecting real clinic use in Asia, suggest that around half of all patients require second combination ART by 3 years after treatment initiation.In South and South-East Asia the nu
The Significance of HIV ‘Blips’ in Resource-Limited Settings: Is It the Same? Analysis of the Treat Asia HIV Observational Database (TAHOD) and the Australian HIV Observational Database (AHOD)  [PDF]
Rupa Kanapathipillai, Hamish McManus, Adeeba Kamarulzaman, Poh Lian Lim, David J. Templeton, Matthew Law, Ian Woolley
PLOS ONE , 2014, DOI: 10.1371/journal.pone.0086122
Abstract: Introduction Magnitude and frequency of HIV viral load blips in resource-limited settings, has not previously been assessed. This study was undertaken in a cohort from a high income country (Australia) known as AHOD (Australian HIV Observational Database) and another cohort from a mixture of Asian countries of varying national income per capita, TAHOD (TREAT Asia HIV Observational Database). Methods Blips were defined as detectable VL (≥ 50 copies/mL) preceded and followed by undetectable VL (<50 copies/mL). Virological failure (VF) was defined as two consecutive VL ≥50 copies/ml. Cox proportional hazard models of time to first VF after entry, were developed. Results 5040 patients (AHOD n = 2597 and TAHOD n = 2521) were included; 910 (18%) of patients experienced blips. 744 (21%) and 166 (11%) of high- and middle/low-income participants, respectively, experienced blips ever. 711 (14%) experienced blips prior to virological failure. 559 (16%) and 152 (10%) of high- and middle/low-income participants, respectively, experienced blips prior to virological failure. VL testing occurred at a median frequency of 175 and 91 days in middle/low- and high-income sites, respectively. Longer time to VF occurred in middle/low income sites, compared with high-income sites (adjusted hazards ratio (AHR) 0.41; p<0.001), adjusted for year of first cART, Hepatitis C co-infection, cART regimen, and prior blips. Prior blips were not a significant predictor of VF in univariate analysis (AHR 0.97, p = 0.82). Differing magnitudes of blips were not significant in univariate analyses as predictors of virological failure (p = 0.360 for blip 50–≤1000, p = 0.309 for blip 50–≤400 and p = 0.300 for blip 50–≤200). 209 of 866 (24%) patients were switched to an alternate regimen in the setting of a blip. Conclusion Despite a lower proportion of blips occurring in low/middle-income settings, no significant difference was found between settings. Nonetheless, a substantial number of participants were switched to alternative regimens in the setting of blips.
Failure to prescribe pneumocystis prophylaxis is associated with increased mortality, even in the cART era: results from the Treat Asia HIV observational database
Lim Poh-Lian,Zhou Jialun,Ditangco Rossana A,Law Matthew G
Journal of the International AIDS Society , 2012, DOI: 10.1186/1758-2652-15-1
Abstract: Background Pneumocystis jiroveci pneumonia (PCP) prophylaxis is recommended for patients with CD4 counts of less than 200 cells/mm3. This study examines the proportion of patients in the TREAT Asia HIV Observational Database (TAHOD) receiving PCP prophylaxis, and its effect on PCP and mortality. Methods TAHOD patients with prospective follow up had data extracted for prophylaxis using co-trimoxazole, dapsone or pentamidine. The proportion of patients on prophylaxis was calculated for each calendar year since 2003 among patients with CD4 counts of less than 200 cells/mm3. The effect of prophylaxis on PCP and survival were assessed using random-effect Poisson regression models. Results There were a total of 4050 patients on prospective follow up, and 90% of them were receiving combination antiretroviral therapy. Of those with CD4 counts of less than 200 cells/mm3, 58% to 72% in any given year received PCP prophylaxis, predominantly co-trimoxazole. During follow up, 62 patients developed PCP (0.5 per 100 person-years) and 169 died from all causes (1.36/100 person-years). After stratifying by site and adjusting for age, CD4 count, CDC stage and antiretroviral treatment, those without prophylaxis had no higher risk of PCP, but had a significantly higher risk of death (incident rate ratio 10.8, p < 0.001). PCP prophylaxis had greatest absolute benefit in patients with CD4 counts of less than 50 cells/mm3, lowering mortality rates from 33.5 to 6.3 per 100 person-years. Conclusions Approximately two-thirds of TAHOD patients with CD4 counts of less than 200 cells/mm3 received PCP prophylaxis. Patients without prophylaxis had significantly higher mortality, even in the era of combination ART. Although PCP may be under-diagnosed, these data suggest that prophylaxis is associated with important survival benefits.
Risk and prognostic significance of tuberculosis in patients from The TREAT Asia HIV Observational Database
Jialun Zhou, Julian Elliott, Patrick CK Li, Poh Lim, Sasisopin Kiertiburanakul, Nagalingeswaran Kumarasamy, Tuti Merati, Sanjay Pujari, Yi-Ming A Chen, Praphan Phanuphak, Saphonn Vonthanak, Thira Sirisanthana, Somnuek Sungkanuparph, Christopher KC Lee, Adeeba Kamarulzaman, Shinichi Oka, Fujie Zhang, Goa Tau, Rossana Ditangco
BMC Infectious Diseases , 2009, DOI: 10.1186/1471-2334-9-46
Abstract: The risk of TB diagnosis after recruitment was assessed in patients with prospective follow-up. TB diagnosis was fitted as a time-dependent variable in assessing overall survival.At baseline, 22% of patients were diagnosed with TB. TB incidence was 1.98 per 100 person-years during follow up, with predictors including younger age, lower recent CD4 count, duration of antiretroviral treatment, and living in high TB burden countries. Among 3279 patients during 6968 person-years, 142 died (2.04 per 100 person-years). Compared to patients with CDC category A or B illness only, mortality was marginally higher in patients with single Non-TB AIDS defining illness (ADI), or TB only (adjusted HR 1.35, p = 0.173) and highest in patients with multiple non-TB AIDS or both TB and other ADI (adjusted HR 2.21, p < 0.001).The risk of TB diagnosis was associated with increasing immunodeficiency and partly reduced by antiretroviral treatment. The prognosis of developing TB appeared to be similar to that following a diagnosis of other non-TB ADI.The use of highly active antiretroviral therapy (HAART) has led to dramatic reductions in morbidity and mortality in HIV patients [1,2]. However, tuberculosis (TB) remains a common opportunistic infections and a major cause of death among patients with HIV, especially in sub-Saharan African and Asian countries [3-5], where there is a high background prevalence of TB [5-7].The risk of TB in HIV-infected patients and the impact of TB diagnosis on disease progression in HIV infected patients have been well described in Africa [3,8-10]. The Asia-Pacific region has a large burden of both tuberculosis [7], with nearly 5 million prevalent cases and over 3 million new cases in 2006, and HIV, with an estimated 5 million people living with HIV and 380,000 new infections occurring in 2007 [11]. It is estimated that 2.5 million people are living with both infections in the region [5]. Despite the importance of these inter-related epidemics in the region, fe
Loss to Followup in HIV-Infected Patients from Asia-Pacific Region: Results from TAHOD  [PDF]
Jialun Zhou,Junko Tanuma,Romanee Chaiwarith,Christopher K. C. Lee,Matthew G. Law,Nagalingeswaran Kumarasamy,Praphan Phanuphak,Yi-Ming A. Chen,Sasisopin Kiertiburanakul,Fujie Zhang,Saphonn Vonthanak,Rossana Ditangco,Sanjay Pujari,Jun Yong Choi,Tuti Parwati Merati,Evy Yunihastuti,Patrick C. K. Li,Adeeba Kamarulzaman,Van Kinh Nguyen,Thi Thanh Thuy Pham,Poh Lian Lim
AIDS Research and Treatment , 2012, DOI: 10.1155/2012/375217
Abstract: This study examined characteristics of HIV-infected patients in the TREAT Asia HIV Observational Database who were lost to follow-up (LTFU) from treatment and care. Time from last clinic visit to 31 March 2009 was analysed to determine the interval that best classified LTFU. Patients defined as LTFU were then categorised into permanently LTFU (never returned) and temporary LTFU (re-entered later), and these groups compared. A total of 3626 patients were included (71% male). No clinic visits for 180 days was the best-performing LTFU definition (sensitivity 90.6%, specificity 92.3%). During 7697 person-years of follow-up, 1648 episodes of LFTU were recorded (21.4 per 100-person-years). Patients LFTU were younger ( ), had HIV viral load ≥500?copies/mL or missing ( ), had shorter history of HIV infection ( ), and received no, single- or double-antiretroviral therapy, or a triple-drug regimen containing a protease inhibitor ( ). 48% of patients LTFU never returned. These patients were more likely to have low or missing haemoglobin ( ), missing recent HIV viral load ( ), negative hepatitis C test ( ), and previous temporary LTFU episodes ( ). Our analyses suggest that patients not seen at a clinic for 180 days are at high risk of permanent LTFU, and should be aggressively traced. 1. Introduction Loss to followup (LTFU) in patients receiving antiretroviral therapy can cause serious consequences such as discontinuation of treatment and increased risk of death [1–3]. At a program level, LTFU can make it difficult to evaluate outcomes of treatment and care [4, 5]. In resource-limited settings, where treatment has become rapidly available following the rollout of antiretroviral therapy, LTFU presents even more challenging obstacles that require special consideration and approaches [6, 7]. One of the key questions in patient followup is how to define a patient as LTFU. This has varied in studies conducted in different settings [8–10]. Defining LTFU using a very early threshold, for example, a patient with no clinic visit in the last three months, may result in many patients being considered as LTFU who would return to clinic naturally at a later date. Defining LTFU with a long threshold, for example, one year, may mean delaying too long before any effort is made to track patients potentially at risk of LTFU. The majority of research into LTFU in HIV-infected patients receiving antiretroviral treatment in resource-limited settings has been conducted in the sub-Saharan Africa region [3, 10–13]. A few studies have been conducted among Asian, mostly female, patients
2010 ASCO Annual Meeting: progress in difficult-to-treat cancers
Günther J Wiedemann,Wolfgang Wagner
European Journal of Oncology Pharmacy , 2010,
Abstract: The 46th Annual Meeting of the American Society of Clinical Oncology took place in June 2010 in Chicago, USA. More than 30,000 specialists discussed the latest innovations in research, quality, practice and technology in cancer. Here we highlight the most significant advances in difficult-to-treat cancers [2].
Human papillomavirus type 58: the unique role in cervical cancers in East Asia
Paul KS Chan
Cell & Bioscience , 2012, DOI: 10.1186/2045-3701-2-17
Abstract: A high prevalence of HPV58 among squamous cell carcinoma has been reported from China (28% in Shanghai, 10% in Hong Kong and 10% in Taiwan) and other countries in East Asia including Korea (16%) and Japan (8%). HPV58 ranks the third in Asia overall, but contributes to only 3.3% of cervical cancers globally. The reasons for a difference in disease attribution may lie on the host as well as the virus itself. HLA-DQB1*06 was found to associate with a higher risk of developing HPV58-positive cervical neoplasia in Hong Kong women, but not neoplasia caused by other HPV types. An HPV58 variant (E7 T20I, G63S) commonly detected in Hong Kong was found to confer a 6.9-fold higher risk of developing cervical cancer compared to other variants. A study involving 15 countries/cities has shown a predilection in the distribution of HPV58 variant lineages. Sublineage A1, the prototype derived from a cancer patient in Japan, was rare worldwide except in Asia.HPV58 accounts for a larger share of disease burden in East Asia, which may be a result of differences in host genetics as well as the oncogenicity of circulating variants. These unique characteristics of HPV58 should be considered in the development of next generation vaccines and diagnostic assays.Human papillomavirus (HPV) plays a necessary, though insufficient, role in the development of cervical cancer, which is the third most common cancer in women worldwide, just following breast and colorectal cancers [1,2]. It has been estimated that about 530 000 new cases and 275 000 deaths from the disease occurred in 2008. The incidence of cervical cancer varies dramatically across the world, which is mainly related to the availability and accessibility of cervical screening programs. Most places in South America and South and West Africa have an age-standardized incidence above 20 per 100 000 women per year, and some places in these regions have reached 40 per 100 000 women per year. In contrast, the age-standardized incidence rates
Quercetin: A Promising Flavonoid with a Dynamic Ability to Treat Various Diseases, Infections, and Cancers  [PDF]
Aaron J. Smith, John Oertle, Dan Warren, Dino Prato
Journal of Cancer Therapy (JCT) , 2016, DOI: 10.4236/jct.2016.72010
Abstract: Quercetin is a multifaceted dietary flavonoid with a multitude of biologic activities that can be used to treat various ailments. These include cancer, bacterial and viral infections, cardiovascular disease, and diabetes. A greater emphasis on cancer is discussed within this paper by highlighting some of the beneficial qualities of quercetin without including other related dietary flavonoids and quercetin analogs. In vitro and in vivo analysis are evaluated without making recommendations on dosage, dosing regiments, or administration since quercetin has not been subjected to rigorous clinical trials despite the significant amount of research that has been conducted with quercetin.
Trends in CD4 counts in HIV-infected patients with HIV viral load monitoring while on combination antiretroviral treatment: results from The TREAT Asia HIV Observational Database
Jialun Zhou, Thira Sirisanthana, Sasisopin Kiertiburanakul, Yi-Ming A Chen, Ning Han, Poh_Lian Lim, Nagalingeswaran Kumarasamy, Jun Choi, Tuti Merati, Evy Yunihastuti, Shinichi Oka, Adeeba Kamarulzaman, Praphan Phanuphak, Christopher KC Lee, Patrick CK Li, Sanjay Pujari, Vanthanak Saphonn, Matthew G Law
BMC Infectious Diseases , 2010, DOI: 10.1186/1471-2334-10-361
Abstract: Treatment-naive HIV-infected patients who started cART with three or more and had three or more CD4 count and HIV VL tests were included. CD4 count slopes were expressed as changes of cells per microliter per year. Predictors of CD4 count slopes from 6 months after initiation were assessed by random-effects linear regression models.A total of 1676 patients (74% male) were included. The median time on cART was 4.2 years (IQR 2.5-5.8 years). In the final model, CD4 count slope was associated with age, concurrent HIV VL and CD4 count, disease stage, hepatitis B or C co-infection, and time since cART initiation. CD4 count continues to increase with HIV VL up to 20 000 copies/mL during 6-12 months after cART initiation. However, the HIV VL has to be controlled below 5 000, 4 000 and 500 copies/mL for the CD4 count slope to remain above 20 cells/microliter per year during 12-18, 18-24, and beyond 24 months after cART initiation.After cART initiation, CD4 counts continued to increase even when the concurrent HIV VL was detectable. However, HIV VL needed to be controlled at a lower level to maintain a positive CD4 count slope when cART continues. The effect on long-term outcomes through the possible development of HIV drug resistance remains uncertain.Studies show that latent infection of CD4 cells provides a mechanism for lifelong persistence of HIV-1, even in patients on effective anti-retroviral therapy [1]. To suppress viral replication so that the VL is below the level of detection with standard assays is thus one of the aims at the start of antiretroviral treatment. Maximal and durable suppression of HIV VL prevents or delays development of drug resistant mutations, preserves CD4 cells, and eventually results in better clinical outcomes. According to the US guidelines, if HIV VL suppression is not achieved, it is necessary to change to a new regimen, a second or third line regimen, with at least two active drugs [2].HIV-infected patients in most developing countries h
Human epidermal growth factor receptor-2 in oesophageal cancers: An observational study  [cached]
Hazem Al-Momani,Rachel Barnes,Ahmed El-Hadi,Rachit Shah
World Journal of Gastroenterology , 2012, DOI: 10.3748/wjg.v18.i44.6447
Abstract: AIM: To determine the incidence of human epidermal growth factor receptor 2 (HER2) over expression in oesophageal cancers. METHODS: A retrospective study, of one hundred consecutive cases of endoscopic histological samples of oesophageal cancers from a single British cancer network were included. Cancer cases were diagnosed between April 2007 and June 2010. HER2 over expression was assessed using immunohistochemistry, those that scored “0” and “+1” were considered “negative” for HER2; those that scored “+3” were considered “Positive”. Cases that were scored “+2” on immunohistochemistry further went on to have HER2 gene analysis using the Ventana HER brightfield dual-colour in situ hybridisations (HER B DISH) assay and either came back to be positive or negative for HER2 over expression. Overall survival was measured from date of histological diagnosis until date of death. 93% of the cases were followed up till five years or death, and all were followed up till two years. Cases of gastro-oesophageal junctional tumours were excluded. RESULTS: The median age of our sample was 66 years (range: 38-91 years). Eighty one were male and 19 female. Ninety-one of the cases were adenocarcinoma of the oesophagus and the rest were cases of squamous cell carcinoma. The anatomical distribution of the tumours was; upper oesophagus 2, middle oesophagus 11, and 87 were in the lower oesophagus. Operative resection was completed in 15 cases; seven cases had attempted surgical resections, i.e., open and close, 33 patients received definitive chemo-radiation and 52 had palliative treatment. Twenty-five of the cancers showed evidence of HER2 over expression, all were adenocarcinomas. Of the 25 cases that showed evidence of HER2 over expression, 21 (84%) were located in the lower third of the oesophagus. On staging, 24 out of the 25 HER2 positive cases were at stage 3 or more (13 at stage 3 and 11 at stage 4), For HER2 negative cases 37 were at stage 3 and 32 were staged as stage 4. Seventeen out of twenty five cases (68%) with HER2 over expression received palliative therapy, in comparison to thirty five out of seventy five (46.7%) in tumours not expressing HER2. No significant difference in overall survival was demonstrated between patients whose cancers showed evidence of HER2 over expression and those who did not; median overall survival for HER2 positive tumours was 15 mo (95%CI, 11-19 mo) compared to 13 mo (95%CI, 9-17 mo) for HER2 negative ones. Two years cumulative survival for cases with HER2 over expression was 33.7% compared to 31.6% in cases without HER2 over expres
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